Dennis Bier - Academia.edu (original) (raw)
Papers by Dennis Bier
Nutrients
The last decade has seen nearly 20 papers reviewing the totality of the data on saturated fats an... more The last decade has seen nearly 20 papers reviewing the totality of the data on saturated fats and cardiovascular outcomes, which, altogether, have demonstrated a lack of rigorous evidence to support continued recommendations either to limit the consumption of saturated fatty acids or to replace them with polyunsaturated fatty acids. These papers were unfortunately not considered by the process leading to the most recent U.S. Dietary Guidelines for Americans, the country’s national nutrition policy, which recently reconfirmed its recommendation to limit saturated fats to 10% or less of total energy intake, based on insufficient and inconsistent evidence. Continuation of a cap on saturated fat intake also fails to consider the important effects of the food matrix and the overall dietary pattern in which saturated fatty acids are consumed.
Applied Physiology, Nutrition, and Metabolism
Given the challenges with nutrition research, the Canadian Nutrition Society and Intertek Health ... more Given the challenges with nutrition research, the Canadian Nutrition Society and Intertek Health Sciences Inc held an expert consultation in late 2019 to discuss the development and implementation of best practices for clinical trials on whole foods. Key challenges in the design, interpretation, and reporting of clinical efficacy studies on whole foods and opportunities for the future development of best practices are reported. Novelty: Outlines existing tools, resources, and checklists for clinical nutrition trials and provides clear and tangible steps to develop best practices for studies on whole foods.
Annual Review of Nutrition
Although I am now officially an alumnus of Rutgers New Jersey Medical School, I actually attended... more Although I am now officially an alumnus of Rutgers New Jersey Medical School, I actually attended Seton Hall College of Medicine in Jersey City, New Jersey. During my senior year, the school changed from a private school to a state institution, becoming New Jersey College of Medicine. Because this change was associated with some disruption due to movement of clinical facilities from Jersey City to Newark, I spent a large fraction of my senior year on the Harriet Lane pediatric service at Johns Hopkins Hospital and on the Boston University medical service at Boston City Hospital. At the end of my senior year, I received a diploma from New Jersey College of Medicine, a school at which I spent almost no time. In the following 47 years, the school underwent a number of name changes, formally becoming part of Rutgers in 2013. I find this hopefully final resting place an excellent one both because of the quality of the institution itself and because none of the classical, pre-Revolution colonial colleges with medical schools would likely have considered me a serious candidate for admission at the time I sought entry. As I prepared to complete my medical school education, I was seriously committed to remaining at East Coast academic institutions for my house officer training, having lived my entire life in the Northeast after my birth in Hoboken, New Jersey. For this reason, all but one of the hospitals to which I applied for pediatric house staff training were associated with the big name medical schools from Baltimore to Boston along the East Coast. Given that I had just spent a highly productive period at Johns Hopkins, I had convinced myself that I would match to the Harriet Lane pediatric service. As fate would have it, during the application period one of my sisters was married in California, and I visited the University of California, San Francisco (UCSF), after I attended the wedding. I did so because I knew Melvin M. Grumbach, an internationally known pediatric endocrinologist from Columbia University, had just accepted the chairmanship of the Department of Pediatrics. I had also heard that Abraham M. Rudolph, another international superstar from the East Coast, had been recruited to the department as its new director of the Division of Pediatric Cardiology. Thus, because San Francisco also appeared to be an exciting place to live in the mid-1960s, I included UCSF as the only non-East Coast school on my match list. Imagine my surprise on Match Day when I learned that I had been matched to UCSF. In retrospect, it was the most important event in my life not only because I met my wife at UCSF, but also because the academic physician scientists who mentored me there paved the road on which I built my subsequent career. While a medical student, I had developed a serious interest in the role of intermediary metabolism in the pathogenesis of diseases. In part, this was because it was the era of intense biochemical delineation of the metabolic derangements in the classical inborn errors of metabolism, and I was increasingly interested in clinical metabolic problems. My interest was due in part to the academic scholarly direction encouraged by my faculty mentor at Seton Hall, Theodore Kushnick, a professor of pediatrics with an eidetic memory who knew, in minute detail, every clinical and biochemical finding in children with inborn metabolic disorders. During my house staff training, my desire to become an academic physician scientist became firmly established owing to the exemplary models of physician scientists such as Mel Grumbach and Selna L. Kaplan in pediatric endocrinology, Abe Rudolph and Julien I.E. Hoffman in pediatric cardiology, and William H. Tooley in neonatology who showed by daily example that physicians could deliver the highest-quality clinical care while conducting patient-oriented research into the www.annualreviews.org • Nutrition from the Inside Out 3
Advances in nutrition (Bethesda, Md.), 2017
A large body of evidence supports the notion that incorrect or insufficient nutrition contributes... more A large body of evidence supports the notion that incorrect or insufficient nutrition contributes to disease development. A pivotal goal is thus to understand what exactly is appropriate and what is inappropriate in food ingestion and the consequent nutritional status and health. The effective application of these concepts requires the translation of scientific information into practical approaches that have a tangible and measurable impact at both individual and population levels. The agenda for the future is expected to support available methodology in nutrition research to personalize guideline recommendations, properly grading the quality of the available evidence, promoting adherence to the well-established evidence hierarchy in nutrition, and enhancing strategies for appropriate vetting and transparent reporting that will solidify the recommendations for health promotion. The final goal is to build a constructive coalition among scientists, policy makers, and communication pro...
Acta Paediatrica, Mar 31, 1991
This study was conducted to investigate the interactions between growth hormone (GH) and insulin-... more This study was conducted to investigate the interactions between growth hormone (GH) and insulin-like growth factor-I (IGF-I) on progesterone (P4) secretion by porcine luteal cells cultured in vitro. Cells isolated from corpora lutea (CL) collected at three different periods of the luteal phase (CL1 - early luteal phase; CL2 - middle luteal phase and CL3 - late luteal phase) were incubated with different doses of GH (10, 100 or 200 ng/ml). After 48 h cultures were terminated and the media were frozen until further P4 concentration analysis. GH (100 ng/ml) increased P4 secretion by CL1 and CL2 and had no effect on CL3. In separate studies these cells were treated for 48 h with IGF-I alone or with GH combined with IGF-I. IGF-I alone increased basal P4 secretion only by cells collected from CL1 while concurrent treatment with GH had no effect on P4 secretion by any type of CL. To investigate the possible mechanism of GH and IGF-I mediated induction of P4 secretion, an inhibitory study was conducted. In this experiment, luteal cells collected from CL1 were cultured in the absence or presence of cycloheximide (an inhibitor of protein synthesis) or actinomycin D (an inhibitor of DNA transcription). Cycloheximide or actinomycin D completely blocked the stimulatory effect of both GH and IGF-I on P4 production but did not reduce basal progesterone secretion suggesting involvement of gene transcription and translation in the GH and IGF-I action on luteal cells. Additionally, the activity of 3ß-hydroxysteroid dehydrogenase (3ß-HSD) under the influence of GH added alone or together with IGF was measured by the conversion of pregnenolone to progesterone. Stimulation of P4 secretion in P5-treated cells in GH-stimulated cultures was not observed, however, high stimulatory effect was noted in IGF-I treated cultures. In conclusion, the present studies indicate that there is direct and cycle stage dependent influence of GH and IGF-I on steroidogenesis in porcine luteal cells. It is suggested that both IGF and GH may exert some regulatory action during CL development in the pig.
Federation Proceedings, Sep 1, 1982
During the last two decades, in parallel with the growth of modern electronics, several new techn... more During the last two decades, in parallel with the growth of modern electronics, several new techniques have been developed for measuring stable isotopic enrichments in biochemistry and medicine. The development and potential of these techniques are discussed. Of these methods, mass spectrometry has been developed and refined the fullest to quantitate stable isotope tracers in very minute samples and for very large dilutions of tracer. No single mass spectrometric technique can measure this entire range, and different techniques are used for different applications. Examples of the different methods are presented for determining whole-body amino acid and protein dynamics in humans with stable isotopically labeled amino acid tracers.
Med Sci Sport Exercise, 1981
Wolters Kluwer Health may email you for journal alerts and information, but is committed to maint... more Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining your privacy and will not share your personal information without your express consent. For more information, please refer to our Privacy Policy. ... Skip Navigation Links Home > 1981 - ...
Acta Diabetologica Latina, 1990
Isotope dilution studies of ketone body (KB) turnover have usually been performed using a single ... more Isotope dilution studies of ketone body (KB) turnover have usually been performed using a single 14C tracer and the so called 'combined KB specific activity'. By definition, this approach does not allow to evaluate the individual kinetics of acetoacetate (AcAc) and 3-hydroxybutyrate (R-BHB) which is feasible only using the separate administration of 14C tracer AcAc and R-BHB. In the present study we followed a different approach using the simultaneous administration in vivo of [1,2,13C2] AcAc and m [1,2,3,4(13)C4] R-BHB which allows to evaluate the individual kinetics of the two KB in the some study, thus minimizing the magnitude of blood sampling and the potential changes in the metabolic conditions of each subject. The four isotopic 13C/12C KB ratios of AcAc and R-BHB tracer and tracee blood concentrations along with the fluorimetric measurement of 12C concentrations were determined in each blood sample. Using compartmental analysis following single dose bolus injection the production rate of KB was 206 +/- 57 mumol/min/1.73 m2 (mean +/- SD). The turnover rate of KB using noncompartmental analysis, during continuous infusion in a separate study was 294 +/- 41. The plasma clearance rates of AcAc and R-BHB were 1966 +/- 502 and 1443 +/- ml/min/1.73 m2, respectively. The mean residence time was 17 +/- 3 min and the total distribution volume 20 +/- 9.7 l/m2. We conclude that: (1) stable isotope tracer infusion allows the contemporary in vivo administration of the two KB and the simultaneous assessment of individual AcAc and R-BHB kinetics; (2) the estimated compartmental and noncompartmental parameters of KB turnover were similar to those observed in normal overnight fasting subjects following separate radioactive tracer injections.
Context: Adolescent obesity is a serious public health concern. Objective: The aim of the study w... more Context: Adolescent obesity is a serious public health concern. Objective: The aim of the study was to determine whether obese adolescents can adapt metabolically to changes in dietary macronutrient intake. Patients and Design: Using a random cross-over design, 13 healthy obese volunteers (six boys and seven girls; age, 14.7 Ϯ 0.3 yr; body mass index, 34 Ϯ 1 kg/m 2 ; body fat, 42 Ϯ 1%) were studied twice after 7 d of isocaloric, isonitrogenous diets with 60% carbohydrate (CHO) and 25% fat (high CHO), or 30% CHO and 55% fat (low CHO). Main Outcome Measures and Methods: Glucose metabolism, insulin sensitivity, and first-and second-phase insulin secretory indices were measured by stable isotope techniques and the stable labeled iv glucose tolerance test. The results were compared with those of previously studied lean adolescents. Results: Obese adolescents increased first-and second-phase insulin secretory indices by 18 (P ϭ 0.05) and 36% (P ϭ 0.05), respectively, to maintain normoglycemia during the high-CHO diet because they failed to increase insulin sensitivity as did the lean adolescents. Regardless of diet, in obese adolescents, insulin sensitivity was half (P Ͻ 0.05) and first-and second-phase insulin secretory indices twice (P Ͻ 0.01), compared with the the corresponding values in lean subjects. In obese adolescents, gluconeogenesis increased by 32% during the low-CHO (high-fat diet) (P Ͻ 0.01). Conclusion: In obese adolescents, insulin secretory demands were increased regardless of diet. Failure to increase insulin sensitivity while receiving a high-CHO diet required a further increase in insulin secretion, which may lead to earlier -cell failure. A low-CHO/high-fat diet resulted in increased gluconeogenesis, which may be a prelude to the increased glucose production and hyperglycemia observed in type 2 diabetics.
Obesity, 2009
Given the increase in the incidence of insulin resistance, obesity, and type 2 diabetes in childr... more Given the increase in the incidence of insulin resistance, obesity, and type 2 diabetes in children and adolescents, it would be of paramount importance to assess quantitative indices of insulin secretion and action during a physiological perturbation, such as a meal or an oral glucose-tolerance test (OGTT). A minimal model method is proposed to measure quantitative indices of insulin secretion and action in adolescents from an oral test. A 7 h, 21-sample OGTT was performed in 11 adolescents. The C-peptide minimal model was identified on C-peptide and glucose data to quantify indices of β-cell function: static Φ s and dynamic Φ d responsivity to glucose from which total responsivity Φ was also measured. The glucose minimal model was identified on glucose and insulin data to estimate insulin sensitivity, S I , which was compared to a reference measure, S I ref , provided by a tracer method. Disposition indices, which adjust insulin secretion for insulin action, were then calculated. Indices of β-cell function were Φ s = 51.35 ± 8.89 × 10-9 min-1 , Φ d = 1,392 ± 258 × 10-9 , and Φ = 82.09 ± 17.70 × 10-9 min-1. Insulin sensitivity was S I = 14.19 ± 2.73 × 10-4 , not significantly different from S I ref = 14.96 ± 3.04 × 10-4 dl/kg. min per μU/ml, and well correlated: r = 0.98, P < 0.0001, thus indicating that S I can be accurately measured from an oral test. Disposition indices were DI s = 1,040 ± 201 × 10-14 dl/kg/min 2 per pmol/l, DI d = 33,178 ± 10,720 × 10-14 dl/kg/min per pmol/l, DI = 1,844 ± 522 × 10-14 dl/kg/min 2 per pmol/l. Virtually the same minimal model assessment was obtained with a reduced 3 h, 9-sample protocol. OGTT interpreted with C-peptide and glucose minimal model has the potential to provide novel insight regarding the regulation of glucose metabolism in adolescents, and to evaluate the effect of obesity and interventions such as diet and exercise.
Nestlé Nutrition Workshop Series: Pediatric Program, 2008
The prevention and treatment of childhood obesity have proven to be extremely difficult problems.... more The prevention and treatment of childhood obesity have proven to be extremely difficult problems. Since the equation for maintaining energy balance is an extremely simple one, having only two terms, 'energy in' and 'energy out', the difficulties encountered in its application for obesity management are not immediately obvious. Among the problems that make practical application of the energy balance equation more difficult than expected are: (1) the precise feedback control system that is designed to maintain weight within a given range; (2) the aggressive resistance of the system to attempts to exceed its boundaries; (3) inaccurate assessment of energy intake in practice; (4) the dominant role of genes in determining body weight; (5) the polygenic nature of obesity and the fact that any single gene accounts for a small fraction of the genetic variation in weight; (6) underestimation of the genetic contribution to the current 'epidemic' of obesity; (7) the fact that 'modifiable' risk factors may be less modifiable than expected; (8) appreciation that family role modeling may be less influential than anticipated, and (9) the realization that our knowledge about the development of physical activity behaviors in childhood is extremely limited.
Principles of Perinatal—Neonatal Metabolism, 1998
The American journal of physiology
ABSTRACT
Critical reviews in food science and nutrition, Jan 16, 2015
Historically, the so-called "lipid hypothesis" has focused on the detrimental role of s... more Historically, the so-called "lipid hypothesis" has focused on the detrimental role of saturated fats per se in enhancing the risks of cardiovascular disease. Recently, a body of new information and systematic analyses of available data have questioned simple interpretation of the relationship of dietary saturated fats and of individual saturated fatty acids to CVD risk. Thus, current assessments of risks due to dietary fat consumption that emphasize the confounding nature of the dietary macronutrients substituted for dietary saturated fats and give broader recognition to the effect of patterns of food intake as a whole are the most productive approach to an overall healthy diet.
Nestlé Nutrition workshop series. Paediatric programme, 2008
The newborn is first colonized by microbes at birth. The colonizing bacteria originate mainly fro... more The newborn is first colonized by microbes at birth. The colonizing bacteria originate mainly from the mother's gut, vaginal tract and skin. The origin of the microbiota and its development depend on genetics, mode of delivery, early feeding strategies and the hygienic conditions around the child. The indigenous microbiota of an infant's gastrointestinal tract is modulated through contact and interaction with the microbiota of the parents and the infant's immediate environment. After delivery breastfeeding continues to enhance the original inoculum by specific lactic acid bacteria and bifidobacteria and bacteria from the mother's skin enabling the infant gut microbiota to be dominated by bifidobacteria. These bacteria set the basis for gut microbiotia development and modulation along with breastfeeding and the environmental exposures such as antibiotic administration. Modifying this exposure can take place by probiotic bacteria when breastfeeding is not possible. Thu...
Nestlé Nutrition workshop series. Paediatric programme, 2008
Compared to other periods of life, infancy is a period of rapid growth, but the relative relation... more Compared to other periods of life, infancy is a period of rapid growth, but the relative relationships among rates of linear growth, weight accretion and brain growth vary greatly during the first years of life. Additionally, while the energy requirements for body tissue deposition as a fraction of daily energy needs decrease dramatically during infancy, brain energy demands, measured as the cerebral rate of glucose utilization, increase markedly during the same period. There is now substantial evidence that postnatal growth in infancy is associated with various consequences detrimental to health in adult life, particularly hypertension, cardiovascular disease, obesity and type 2 diabetes, but the relationships vary depending on whether one takes growth to mean statural growth or ponderal growth, as well as on the specific period of infant growth. Recently, several mechanisms have surfaced that might account for the relationships observed. These include epigenetic effects on gene ex...
The Journal of nutrition, 2007
The Journal of nutrition, 2003
Tracer kinetic studies of amino acid metabolism during periods of high amino acid intake should a... more Tracer kinetic studies of amino acid metabolism during periods of high amino acid intake should allow insights into adaptive or maladaptive regulatory mechanisms controlling amino acid catabolic or disposal events before clinically evident effects. The principles of amino acid tracer kinetics have been well defined, but their application to establishing upper safe intake levels has been essentially nonexistent. Similarly, the pharmacology field has well-established disciplines of toxicokinetics (the relationship of toxicant dose and delivery to its site of action) and toxicodynamics (the relationship of toxicant at its site of action and downstream functional consequences), but these principles have not been transferred to the field of amino acid metabolism. In this context, a theoretical framework is presented for tracer kinetic experiments to help establish upper tolerable levels of amino acid infusion and/or ingestion. In addition, experiments to couple specific amino acid intake...
The American journal of physiology, 1993
Muscle mass and function are improved in the elderly during resistance exercise training. These i... more Muscle mass and function are improved in the elderly during resistance exercise training. These improvements must result from alterations in the rates of muscle protein synthesis and breakdown. We determined the rate of quadriceps muscle protein synthesis using the in vivo rate of incorporation of intravenously infused [13C]leucine into mixed-muscle protein in both young (24 yr) and elderly (63-66 yr) men and women before and at the end of 2 wk of resistance exercise training. Before training, the fractional rate of muscle protein synthesis was lower in the elderly than in the young (0.030 +/- 0.003 vs. 0.049 +/- 0.004%/h; P = 0.004) but increased (P < 0.03) to a comparable rate of muscle protein synthesis in both young (0.075 +/- 0.009%/h) and elderly subjects (0.076 +/- 0.011%/h) after 2 wk of exercise. In the elderly, muscle mass, 24-h urinary 3-methylhistidine and creatinine excretion, and whole body protein breakdown rate determined during the [13C]leucine infusion were not ...
Nutrients
The last decade has seen nearly 20 papers reviewing the totality of the data on saturated fats an... more The last decade has seen nearly 20 papers reviewing the totality of the data on saturated fats and cardiovascular outcomes, which, altogether, have demonstrated a lack of rigorous evidence to support continued recommendations either to limit the consumption of saturated fatty acids or to replace them with polyunsaturated fatty acids. These papers were unfortunately not considered by the process leading to the most recent U.S. Dietary Guidelines for Americans, the country’s national nutrition policy, which recently reconfirmed its recommendation to limit saturated fats to 10% or less of total energy intake, based on insufficient and inconsistent evidence. Continuation of a cap on saturated fat intake also fails to consider the important effects of the food matrix and the overall dietary pattern in which saturated fatty acids are consumed.
Applied Physiology, Nutrition, and Metabolism
Given the challenges with nutrition research, the Canadian Nutrition Society and Intertek Health ... more Given the challenges with nutrition research, the Canadian Nutrition Society and Intertek Health Sciences Inc held an expert consultation in late 2019 to discuss the development and implementation of best practices for clinical trials on whole foods. Key challenges in the design, interpretation, and reporting of clinical efficacy studies on whole foods and opportunities for the future development of best practices are reported. Novelty: Outlines existing tools, resources, and checklists for clinical nutrition trials and provides clear and tangible steps to develop best practices for studies on whole foods.
Annual Review of Nutrition
Although I am now officially an alumnus of Rutgers New Jersey Medical School, I actually attended... more Although I am now officially an alumnus of Rutgers New Jersey Medical School, I actually attended Seton Hall College of Medicine in Jersey City, New Jersey. During my senior year, the school changed from a private school to a state institution, becoming New Jersey College of Medicine. Because this change was associated with some disruption due to movement of clinical facilities from Jersey City to Newark, I spent a large fraction of my senior year on the Harriet Lane pediatric service at Johns Hopkins Hospital and on the Boston University medical service at Boston City Hospital. At the end of my senior year, I received a diploma from New Jersey College of Medicine, a school at which I spent almost no time. In the following 47 years, the school underwent a number of name changes, formally becoming part of Rutgers in 2013. I find this hopefully final resting place an excellent one both because of the quality of the institution itself and because none of the classical, pre-Revolution colonial colleges with medical schools would likely have considered me a serious candidate for admission at the time I sought entry. As I prepared to complete my medical school education, I was seriously committed to remaining at East Coast academic institutions for my house officer training, having lived my entire life in the Northeast after my birth in Hoboken, New Jersey. For this reason, all but one of the hospitals to which I applied for pediatric house staff training were associated with the big name medical schools from Baltimore to Boston along the East Coast. Given that I had just spent a highly productive period at Johns Hopkins, I had convinced myself that I would match to the Harriet Lane pediatric service. As fate would have it, during the application period one of my sisters was married in California, and I visited the University of California, San Francisco (UCSF), after I attended the wedding. I did so because I knew Melvin M. Grumbach, an internationally known pediatric endocrinologist from Columbia University, had just accepted the chairmanship of the Department of Pediatrics. I had also heard that Abraham M. Rudolph, another international superstar from the East Coast, had been recruited to the department as its new director of the Division of Pediatric Cardiology. Thus, because San Francisco also appeared to be an exciting place to live in the mid-1960s, I included UCSF as the only non-East Coast school on my match list. Imagine my surprise on Match Day when I learned that I had been matched to UCSF. In retrospect, it was the most important event in my life not only because I met my wife at UCSF, but also because the academic physician scientists who mentored me there paved the road on which I built my subsequent career. While a medical student, I had developed a serious interest in the role of intermediary metabolism in the pathogenesis of diseases. In part, this was because it was the era of intense biochemical delineation of the metabolic derangements in the classical inborn errors of metabolism, and I was increasingly interested in clinical metabolic problems. My interest was due in part to the academic scholarly direction encouraged by my faculty mentor at Seton Hall, Theodore Kushnick, a professor of pediatrics with an eidetic memory who knew, in minute detail, every clinical and biochemical finding in children with inborn metabolic disorders. During my house staff training, my desire to become an academic physician scientist became firmly established owing to the exemplary models of physician scientists such as Mel Grumbach and Selna L. Kaplan in pediatric endocrinology, Abe Rudolph and Julien I.E. Hoffman in pediatric cardiology, and William H. Tooley in neonatology who showed by daily example that physicians could deliver the highest-quality clinical care while conducting patient-oriented research into the www.annualreviews.org • Nutrition from the Inside Out 3
Advances in nutrition (Bethesda, Md.), 2017
A large body of evidence supports the notion that incorrect or insufficient nutrition contributes... more A large body of evidence supports the notion that incorrect or insufficient nutrition contributes to disease development. A pivotal goal is thus to understand what exactly is appropriate and what is inappropriate in food ingestion and the consequent nutritional status and health. The effective application of these concepts requires the translation of scientific information into practical approaches that have a tangible and measurable impact at both individual and population levels. The agenda for the future is expected to support available methodology in nutrition research to personalize guideline recommendations, properly grading the quality of the available evidence, promoting adherence to the well-established evidence hierarchy in nutrition, and enhancing strategies for appropriate vetting and transparent reporting that will solidify the recommendations for health promotion. The final goal is to build a constructive coalition among scientists, policy makers, and communication pro...
Acta Paediatrica, Mar 31, 1991
This study was conducted to investigate the interactions between growth hormone (GH) and insulin-... more This study was conducted to investigate the interactions between growth hormone (GH) and insulin-like growth factor-I (IGF-I) on progesterone (P4) secretion by porcine luteal cells cultured in vitro. Cells isolated from corpora lutea (CL) collected at three different periods of the luteal phase (CL1 - early luteal phase; CL2 - middle luteal phase and CL3 - late luteal phase) were incubated with different doses of GH (10, 100 or 200 ng/ml). After 48 h cultures were terminated and the media were frozen until further P4 concentration analysis. GH (100 ng/ml) increased P4 secretion by CL1 and CL2 and had no effect on CL3. In separate studies these cells were treated for 48 h with IGF-I alone or with GH combined with IGF-I. IGF-I alone increased basal P4 secretion only by cells collected from CL1 while concurrent treatment with GH had no effect on P4 secretion by any type of CL. To investigate the possible mechanism of GH and IGF-I mediated induction of P4 secretion, an inhibitory study was conducted. In this experiment, luteal cells collected from CL1 were cultured in the absence or presence of cycloheximide (an inhibitor of protein synthesis) or actinomycin D (an inhibitor of DNA transcription). Cycloheximide or actinomycin D completely blocked the stimulatory effect of both GH and IGF-I on P4 production but did not reduce basal progesterone secretion suggesting involvement of gene transcription and translation in the GH and IGF-I action on luteal cells. Additionally, the activity of 3ß-hydroxysteroid dehydrogenase (3ß-HSD) under the influence of GH added alone or together with IGF was measured by the conversion of pregnenolone to progesterone. Stimulation of P4 secretion in P5-treated cells in GH-stimulated cultures was not observed, however, high stimulatory effect was noted in IGF-I treated cultures. In conclusion, the present studies indicate that there is direct and cycle stage dependent influence of GH and IGF-I on steroidogenesis in porcine luteal cells. It is suggested that both IGF and GH may exert some regulatory action during CL development in the pig.
Federation Proceedings, Sep 1, 1982
During the last two decades, in parallel with the growth of modern electronics, several new techn... more During the last two decades, in parallel with the growth of modern electronics, several new techniques have been developed for measuring stable isotopic enrichments in biochemistry and medicine. The development and potential of these techniques are discussed. Of these methods, mass spectrometry has been developed and refined the fullest to quantitate stable isotope tracers in very minute samples and for very large dilutions of tracer. No single mass spectrometric technique can measure this entire range, and different techniques are used for different applications. Examples of the different methods are presented for determining whole-body amino acid and protein dynamics in humans with stable isotopically labeled amino acid tracers.
Med Sci Sport Exercise, 1981
Wolters Kluwer Health may email you for journal alerts and information, but is committed to maint... more Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining your privacy and will not share your personal information without your express consent. For more information, please refer to our Privacy Policy. ... Skip Navigation Links Home > 1981 - ...
Acta Diabetologica Latina, 1990
Isotope dilution studies of ketone body (KB) turnover have usually been performed using a single ... more Isotope dilution studies of ketone body (KB) turnover have usually been performed using a single 14C tracer and the so called 'combined KB specific activity'. By definition, this approach does not allow to evaluate the individual kinetics of acetoacetate (AcAc) and 3-hydroxybutyrate (R-BHB) which is feasible only using the separate administration of 14C tracer AcAc and R-BHB. In the present study we followed a different approach using the simultaneous administration in vivo of [1,2,13C2] AcAc and m [1,2,3,4(13)C4] R-BHB which allows to evaluate the individual kinetics of the two KB in the some study, thus minimizing the magnitude of blood sampling and the potential changes in the metabolic conditions of each subject. The four isotopic 13C/12C KB ratios of AcAc and R-BHB tracer and tracee blood concentrations along with the fluorimetric measurement of 12C concentrations were determined in each blood sample. Using compartmental analysis following single dose bolus injection the production rate of KB was 206 +/- 57 mumol/min/1.73 m2 (mean +/- SD). The turnover rate of KB using noncompartmental analysis, during continuous infusion in a separate study was 294 +/- 41. The plasma clearance rates of AcAc and R-BHB were 1966 +/- 502 and 1443 +/- ml/min/1.73 m2, respectively. The mean residence time was 17 +/- 3 min and the total distribution volume 20 +/- 9.7 l/m2. We conclude that: (1) stable isotope tracer infusion allows the contemporary in vivo administration of the two KB and the simultaneous assessment of individual AcAc and R-BHB kinetics; (2) the estimated compartmental and noncompartmental parameters of KB turnover were similar to those observed in normal overnight fasting subjects following separate radioactive tracer injections.
Context: Adolescent obesity is a serious public health concern. Objective: The aim of the study w... more Context: Adolescent obesity is a serious public health concern. Objective: The aim of the study was to determine whether obese adolescents can adapt metabolically to changes in dietary macronutrient intake. Patients and Design: Using a random cross-over design, 13 healthy obese volunteers (six boys and seven girls; age, 14.7 Ϯ 0.3 yr; body mass index, 34 Ϯ 1 kg/m 2 ; body fat, 42 Ϯ 1%) were studied twice after 7 d of isocaloric, isonitrogenous diets with 60% carbohydrate (CHO) and 25% fat (high CHO), or 30% CHO and 55% fat (low CHO). Main Outcome Measures and Methods: Glucose metabolism, insulin sensitivity, and first-and second-phase insulin secretory indices were measured by stable isotope techniques and the stable labeled iv glucose tolerance test. The results were compared with those of previously studied lean adolescents. Results: Obese adolescents increased first-and second-phase insulin secretory indices by 18 (P ϭ 0.05) and 36% (P ϭ 0.05), respectively, to maintain normoglycemia during the high-CHO diet because they failed to increase insulin sensitivity as did the lean adolescents. Regardless of diet, in obese adolescents, insulin sensitivity was half (P Ͻ 0.05) and first-and second-phase insulin secretory indices twice (P Ͻ 0.01), compared with the the corresponding values in lean subjects. In obese adolescents, gluconeogenesis increased by 32% during the low-CHO (high-fat diet) (P Ͻ 0.01). Conclusion: In obese adolescents, insulin secretory demands were increased regardless of diet. Failure to increase insulin sensitivity while receiving a high-CHO diet required a further increase in insulin secretion, which may lead to earlier -cell failure. A low-CHO/high-fat diet resulted in increased gluconeogenesis, which may be a prelude to the increased glucose production and hyperglycemia observed in type 2 diabetics.
Obesity, 2009
Given the increase in the incidence of insulin resistance, obesity, and type 2 diabetes in childr... more Given the increase in the incidence of insulin resistance, obesity, and type 2 diabetes in children and adolescents, it would be of paramount importance to assess quantitative indices of insulin secretion and action during a physiological perturbation, such as a meal or an oral glucose-tolerance test (OGTT). A minimal model method is proposed to measure quantitative indices of insulin secretion and action in adolescents from an oral test. A 7 h, 21-sample OGTT was performed in 11 adolescents. The C-peptide minimal model was identified on C-peptide and glucose data to quantify indices of β-cell function: static Φ s and dynamic Φ d responsivity to glucose from which total responsivity Φ was also measured. The glucose minimal model was identified on glucose and insulin data to estimate insulin sensitivity, S I , which was compared to a reference measure, S I ref , provided by a tracer method. Disposition indices, which adjust insulin secretion for insulin action, were then calculated. Indices of β-cell function were Φ s = 51.35 ± 8.89 × 10-9 min-1 , Φ d = 1,392 ± 258 × 10-9 , and Φ = 82.09 ± 17.70 × 10-9 min-1. Insulin sensitivity was S I = 14.19 ± 2.73 × 10-4 , not significantly different from S I ref = 14.96 ± 3.04 × 10-4 dl/kg. min per μU/ml, and well correlated: r = 0.98, P < 0.0001, thus indicating that S I can be accurately measured from an oral test. Disposition indices were DI s = 1,040 ± 201 × 10-14 dl/kg/min 2 per pmol/l, DI d = 33,178 ± 10,720 × 10-14 dl/kg/min per pmol/l, DI = 1,844 ± 522 × 10-14 dl/kg/min 2 per pmol/l. Virtually the same minimal model assessment was obtained with a reduced 3 h, 9-sample protocol. OGTT interpreted with C-peptide and glucose minimal model has the potential to provide novel insight regarding the regulation of glucose metabolism in adolescents, and to evaluate the effect of obesity and interventions such as diet and exercise.
Nestlé Nutrition Workshop Series: Pediatric Program, 2008
The prevention and treatment of childhood obesity have proven to be extremely difficult problems.... more The prevention and treatment of childhood obesity have proven to be extremely difficult problems. Since the equation for maintaining energy balance is an extremely simple one, having only two terms, 'energy in' and 'energy out', the difficulties encountered in its application for obesity management are not immediately obvious. Among the problems that make practical application of the energy balance equation more difficult than expected are: (1) the precise feedback control system that is designed to maintain weight within a given range; (2) the aggressive resistance of the system to attempts to exceed its boundaries; (3) inaccurate assessment of energy intake in practice; (4) the dominant role of genes in determining body weight; (5) the polygenic nature of obesity and the fact that any single gene accounts for a small fraction of the genetic variation in weight; (6) underestimation of the genetic contribution to the current 'epidemic' of obesity; (7) the fact that 'modifiable' risk factors may be less modifiable than expected; (8) appreciation that family role modeling may be less influential than anticipated, and (9) the realization that our knowledge about the development of physical activity behaviors in childhood is extremely limited.
Principles of Perinatal—Neonatal Metabolism, 1998
The American journal of physiology
ABSTRACT
Critical reviews in food science and nutrition, Jan 16, 2015
Historically, the so-called "lipid hypothesis" has focused on the detrimental role of s... more Historically, the so-called "lipid hypothesis" has focused on the detrimental role of saturated fats per se in enhancing the risks of cardiovascular disease. Recently, a body of new information and systematic analyses of available data have questioned simple interpretation of the relationship of dietary saturated fats and of individual saturated fatty acids to CVD risk. Thus, current assessments of risks due to dietary fat consumption that emphasize the confounding nature of the dietary macronutrients substituted for dietary saturated fats and give broader recognition to the effect of patterns of food intake as a whole are the most productive approach to an overall healthy diet.
Nestlé Nutrition workshop series. Paediatric programme, 2008
The newborn is first colonized by microbes at birth. The colonizing bacteria originate mainly fro... more The newborn is first colonized by microbes at birth. The colonizing bacteria originate mainly from the mother's gut, vaginal tract and skin. The origin of the microbiota and its development depend on genetics, mode of delivery, early feeding strategies and the hygienic conditions around the child. The indigenous microbiota of an infant's gastrointestinal tract is modulated through contact and interaction with the microbiota of the parents and the infant's immediate environment. After delivery breastfeeding continues to enhance the original inoculum by specific lactic acid bacteria and bifidobacteria and bacteria from the mother's skin enabling the infant gut microbiota to be dominated by bifidobacteria. These bacteria set the basis for gut microbiotia development and modulation along with breastfeeding and the environmental exposures such as antibiotic administration. Modifying this exposure can take place by probiotic bacteria when breastfeeding is not possible. Thu...
Nestlé Nutrition workshop series. Paediatric programme, 2008
Compared to other periods of life, infancy is a period of rapid growth, but the relative relation... more Compared to other periods of life, infancy is a period of rapid growth, but the relative relationships among rates of linear growth, weight accretion and brain growth vary greatly during the first years of life. Additionally, while the energy requirements for body tissue deposition as a fraction of daily energy needs decrease dramatically during infancy, brain energy demands, measured as the cerebral rate of glucose utilization, increase markedly during the same period. There is now substantial evidence that postnatal growth in infancy is associated with various consequences detrimental to health in adult life, particularly hypertension, cardiovascular disease, obesity and type 2 diabetes, but the relationships vary depending on whether one takes growth to mean statural growth or ponderal growth, as well as on the specific period of infant growth. Recently, several mechanisms have surfaced that might account for the relationships observed. These include epigenetic effects on gene ex...
The Journal of nutrition, 2007
The Journal of nutrition, 2003
Tracer kinetic studies of amino acid metabolism during periods of high amino acid intake should a... more Tracer kinetic studies of amino acid metabolism during periods of high amino acid intake should allow insights into adaptive or maladaptive regulatory mechanisms controlling amino acid catabolic or disposal events before clinically evident effects. The principles of amino acid tracer kinetics have been well defined, but their application to establishing upper safe intake levels has been essentially nonexistent. Similarly, the pharmacology field has well-established disciplines of toxicokinetics (the relationship of toxicant dose and delivery to its site of action) and toxicodynamics (the relationship of toxicant at its site of action and downstream functional consequences), but these principles have not been transferred to the field of amino acid metabolism. In this context, a theoretical framework is presented for tracer kinetic experiments to help establish upper tolerable levels of amino acid infusion and/or ingestion. In addition, experiments to couple specific amino acid intake...
The American journal of physiology, 1993
Muscle mass and function are improved in the elderly during resistance exercise training. These i... more Muscle mass and function are improved in the elderly during resistance exercise training. These improvements must result from alterations in the rates of muscle protein synthesis and breakdown. We determined the rate of quadriceps muscle protein synthesis using the in vivo rate of incorporation of intravenously infused [13C]leucine into mixed-muscle protein in both young (24 yr) and elderly (63-66 yr) men and women before and at the end of 2 wk of resistance exercise training. Before training, the fractional rate of muscle protein synthesis was lower in the elderly than in the young (0.030 +/- 0.003 vs. 0.049 +/- 0.004%/h; P = 0.004) but increased (P < 0.03) to a comparable rate of muscle protein synthesis in both young (0.075 +/- 0.009%/h) and elderly subjects (0.076 +/- 0.011%/h) after 2 wk of exercise. In the elderly, muscle mass, 24-h urinary 3-methylhistidine and creatinine excretion, and whole body protein breakdown rate determined during the [13C]leucine infusion were not ...