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Papers by peter gregory

Research paper thumbnail of CONTROL OF STOMACH MOTILITY IN THE LLAMA (LA MA GUANACOE F. GLAMA

Quarterly Journal of Experimental Physiology 70, 51 -61, 1985

Manometric and electromyographic recordings of stomach motility were made in five conscious llama... more Manometric and electromyographic recordings of stomach motility were made in five conscious llamas to investigate the influence of distension of the stomach compartments, of temporary cervical vagal blockade and the influence of atropine, acetylcholine and adrenaline. The frequency of A-contractions was slowed by distension of the canal joining compartment 2 (C2) and compartment 3 (C3), or of the proximal region of C3, and either increased and/or reduced by distension of the distal region of C3 or the hind stomach. The number of B-contractions in a cycle was increased according to the degree of distension of the cranial sac of compartment 1 (C 1). B-contractions were also induced by distension of the canal or proximal region of C3 and were inhibited by distension of the distal region of C3 or the hind stomach. Contractions of C3 were not influenced by distension of Cl or C2 but were inhibited by distension of the canal, while distension within C3 caused a local excitation and an inhibition both proximal and distal to the point of stimulation. The hind stomach was only affected by local stimuli. Temporary vagal blockade abolished all contractions of C1, C2, the canal and C3, but had little effect on the motility of the hind stomach. Infusion of atropine (0-01 mg/kg), acetylcholine (7-33 1zg/kg. min) and adrenaline (0 3 Itg/kg. min) inhibited motility in all stomach compartments except the hind stomach where acetylcholine was stimulatory. it is concluded that while the hind stomach may have intrinsic motility, the contractions of Cl, C2, the canal and C3 of the llama stomach are dependent upon a vagal motor nerve supply and that the pattern of contractions observed is regulated at least partially according to the individual degree of distension of each of the stomach compartments.

Research paper thumbnail of Pattern of motility and flow of digesta in the forestomach of the Llama (Lama guanacoe f. glama

J Comp Physiol B 154, 529–533 , 1984

A study of the pattern of stomach motility was made in five conscious llamas. Motility was record... more A study of the pattern of stomach motility was made in five conscious llamas. Motility was recorded continuously by X-radiography, electromyography and/or balloons with pressure transducers, and correlated with outflow of forestomach contents measured by a thermistor. The llama forestomach showed a rhythmic pattern of contractions (motility cycle). A single cycle lasted about 82 s. Evidence is presented that each cycle comprises a single A-and numerous B-contraction sequences. Each motility cycle started with an A-sequence which began with a contraction of the canal between compartment 2 (C2) and compartment 3 (C3). A vigorous contraction of C2 followed, as the pressure in the canal fell below the baseline, then a contraction of the caudal sac of compartment 1 (C1) and another contraction of the canal occurred. The B-sequence of contractions began with a contraction of the cranial sac of C1 at the same time as the second canal contraction, followed by a weak contraction of C2 and finally a contraction of the caudal sac of C1. This B-sequence was repeated a number of times in each motility cycle. Passage of contents from C2 to C3 only occurred as the canal relaxed during the A-contraction. Continuous aborally-directed segmention and peristaltic-like movements were recorded in C3. These contractions occurred at 10 min-1 in the proximal part, and at 5 min-1 in the distal part where they were strongest. In the hind stomach mixing movements could be seen. At the border between C3 and the hind stomach, within a length of 10cm the pH fell from 6 to less than 2. No

Research paper thumbnail of Ibipinabant attenuates β-cell loss in male Zucker diabetic fatty rats independently of its effects on body weight

Diabetes, Obesity and Metabolism 14: 555 – 564,, 2012

Aim: To test the antidiabetic efficacy of ibipinabant, this new cannabinoid receptor 1 (CB1) anta... more Aim: To test the antidiabetic efficacy of ibipinabant, this new cannabinoid receptor 1 (CB1) antagonist was compared with food-restrictioninduced weight loss, rosiglitazone (4 mg/kg) and rimonabant (3 and 10 mg/kg), using parameters of glycaemic control in male Zucker diabetic fatty (ZDF) rats. Methods: Body weight, food and water intake, fasted and non-fasted glucose and insulin, glucose tolerance and glycosylated haemoglobin (HbA1c) were all assessed over the course of the 9-week study. Pancreatic insulin content and islet area were also evaluated. Results: At the end of the study, vehicle-treated ZDF rats were severely hyperglycaemic and showed signs of β-cell decline, including dramatic reductions in unfasted insulin levels. Ibipinanbant (10 mg/kg) reduced the following relative to vehicle controls: fasting glucose (−61%), glucose excursion area under the curve (AUC) in an oral glucose tolerance test (OGTT, −44%) and HbA1c (−50%). Furthermore, non-fasting insulin, islet area and islet insulin content were all increased (71, 40 and 76%, respectively) relative to vehicle controls by the end of the study. All of these effects were similar to those of rimonabant and rosiglitazone, where ibipinabant was slightly more effective than rimonabant at the lowest dose and somewhat less effective than rosiglitazone at all doses. These antidiabetic effects appear independent of weight loss because none of the parameters above were consistently improved by the comparable weight loss induced by food restriction. Conclusions: Ibipinabant may have weight loss-independent antidiabetic effects and may have the potential to attenuate β-cell loss in a model of progressive β-cell dysfunction.

Research paper thumbnail of Prececal digestibility of various sources of starch in minipigs with or without experimentally induced exocrine pancreatic insufficiency

Journal of Animal Science, 2012

Research paper thumbnail of Some cannabinoid receptor ligands and their distomers are direct-acting openers of SUR1 KATP channels

American Journal of Physiology-Endocrinology and Metabolism, 2011

Here, we examined the chronic effects of two cannabinoid receptor-1 (CB1) inverse agonists, rimon... more Here, we examined the chronic effects of two cannabinoid receptor-1 (CB1) inverse agonists, rimonabant and ibipinabant, in hyperinsulinemic Zucker rats to determine their chronic effects on insulinemia. Rimonabant and ibipinabant (10 mg·kg−1·day−1) elicited body weight-independent improvements in insulinemia and glycemia during 10 wk of chronic treatment. To elucidate the mechanism of insulin lowering, acute in vivo and in vitro studies were then performed. Surprisingly, chronic treatment was not required for insulin lowering. In acute in vivo and in vitro studies, the CB1 inverse agonists exhibited acute K channel opener (KCO; e.g., diazoxide and NN414)-like effects on glucose tolerance and glucose-stimulated insulin secretion (GSIS) with approximately fivefold better potency than diazoxide. Followup studies implied that these effects were inconsistent with a CB1-mediated mechanism. Thus effects of several CB1 agonists, inverse agonists, and distomers during GTTs or GSIS studies us...

Research paper thumbnail of {"__content__"=>"Metabolic markers of protein maldigestion after a N test meal in minipigs with pancreatic exocrine insufficiency.", "sup"=>{"__content__"=>"15"}}

American journal of physiology. Gastrointestinal and liver physiology, Feb 1, 2018

The effect of pancreatic exocrine insufficiency (PEI) on protein malabsorption is little document... more The effect of pancreatic exocrine insufficiency (PEI) on protein malabsorption is little documented, partly due to methodological barriers. We aimed to validate biomarkers of protein malabsorption using a N test meal in a minipig model of PEI. Six pancreatic duct-ligated minipigs were used as a model of PEI and four nonoperated animals as a control. All animals were equipped with an ileocecal reentrant cannula. Minipigs were given a test meal containing [N]casein. The PEI animals repeated the test three times, in the absence of any pancreatic enzymes, or after pancreatic substitution at two levels [ A or B: 7,500 or 75,000 (lipase) and 388 or 3881 (protease) FIP U]. Ileal chyme, urine, and blood were collected postprandially. Nitrogen and N were measured in digestive and metabolic pools. We obtained a gradient of ileal protein digestibility from 29 ± 11% in PEI to 89 ± 6% in the controls and a dose- dependent response of enzymes. Insulin and gastric inhibitory polypeptide secretions...

Research paper thumbnail of Glucose homeostasis dependency on acini-islet-acinar (AIA) axis communication: a new possible pathophysiological hypothesis regarding diabetes mellitus

Nutrition & diabetes, Jan 8, 2018

Studies have highlighted the existence of two intra-pancreatic axes of communication: one involve... more Studies have highlighted the existence of two intra-pancreatic axes of communication: one involved in the regulation of enzyme production by insulin-the insular-acinar axis; and another involved in the regulation of insulin release by pancreatic enzymes-the acini-insular axis. Previous studies by our laboratory show that pancreatic enzymes can affect blood glucose homeostasis and insulin secretion independently of their digestive functions, both from the gut lumen and probably from the blood. As a result we would like to introduce here the concept of acini-islet-acinar (AIA) axis communication (feedback), which could play an important role in the development of obesity and diabetes type 2. The AIA feedback links the endocrine and exocrine parts of the pancreas and emphasizes the essential role that the pancreas plays, as a single organ, in the regulation of glucose homeostasis by amylase most probably in gut epithelium and by insulin and glucagon in peripheral blood.

Research paper thumbnail of Experiments suggesting extra-digestive effects of enteral pancreatic amylase and its peptides on glucose homeostasis in a pig model

Scientific reports, Jan 17, 2017

The studies presented were designed to highlight the impact of pancreatic enzymes on glycemic con... more The studies presented were designed to highlight the impact of pancreatic enzymes on glycemic control and insulin response. Blood glucose and plasma insulin levels were monitored after intravenous, oral or direct gut glucose tolerance tests (GTT) in 6 pigs with an intact gastrointestinal tract and in 12 pigs following duodenal-jejunal bypass (DJB) surgery. In the intact pigs, pancreatic enzymes (Creon®) given orally 1 h prior to the GTT, lowered the blood glucose levels during the oral and meal GTT and reduced the plasma insulin response during the intravenous and meal GTT. In DJB pigs, blood glucose and plasma insulin levels were higher following glucose loading into the by-passed biliopancreatic limb as compared to that following glucose loading orally or into the common intestinal limb. Infusion of amylase or amylase peptides together with glucose into the biliopancreatic limb lowered blood glucose levels in DJB pigs. These preliminary data suggest new, extra-digestive, actions o...

Research paper thumbnail of The Pancreatic Duct Ligated (Mini)pig as a Model for Pancreatic Exocrine Insufficiency in Man

Pancreas, 2016

Modern therapy of pancreatic exocrine insufficiency (PEI) using pancreatic enzyme replacement the... more Modern therapy of pancreatic exocrine insufficiency (PEI) using pancreatic enzyme replacement therapy (PERT) has largely been very effective and has greatly helped in improving the nutritional status of patients with PEI and in increasing the life expectancy in cystic fibrosis. It is believed that the use of predictable large animal models could play an important role in assessing and developing new therapies. This article reviews the pancreatic duct ligated (adult) minipig as a chronic model of total PEI, with a detailed look at the influence of PEI and response to PERT on prececal compared to fecal digestibility, to directly investigate effects on protein and starch digestion and absorption. In addition, the piglet with PEI is reviewed as a model for PEI in young patients with the aim of further improving the therapy and nutritional status of young patients with cystic fibrosis.

Research paper thumbnail of Endogenous praecaecal and total tract losses of nitrogen in pancreatic duct-ligated minipigs

Http Dx Doi Org 10 1080 1745039x 2015 1009612, Feb 18, 2015

The pancreatic duct-ligated minipig (PL) is an established model of pancreatic exocrine insuffici... more The pancreatic duct-ligated minipig (PL) is an established model of pancreatic exocrine insufficiency (PEI) with a significant decrease of nutrient digestibility. This study aimed to quantify and compare endogenous losses of nitrogen (N) (ileal and faecal) in minipigs receiving an almost N-free diet. Altogether, 12 Göttingen minipigs (7 PL and 5 control animals) fitted with an re-entrant ileo-caecal fistula were used. In Study 1, ileal digesta was collected over a period of 12 h on seven consecutive days, including one 24 h collection, when animals were fed a diet containing 0.49 g N/kg dry matter (DM). In Study 2, faeces were collected for 10 consecutive days. In Group PL, the amount and DM content of ileal digesta were higher (p < 0.05), while N concentration was lower than in the Control. The ileo-caecal N flux [g/kg DM intake] was about 2.5 times higher in Group PL (5.47 ± 1.15) than in the Control (1.91 ± 0.59) (p < 0.05). The amount of faeces did not differ, but faecal N losses were higher in Group PL (p < 0.05). Endogenous faecal N losses [g N/kg DM intake] of the Control group (1.17 ± 0.72) were comparable with earlier studies, while those of Group PL were 2.6 times higher (3.09 ± 1.34). In contrast, urinary excretion of N did not differ between the Control and Group PL. In conclusion, PEI caused markedly increased endogenous N losses. Therefore, the impact of reduced digestibility of nutrients on endogenous N losses might be relevant for apparent protein digestibility rates and should be taken into account.

Research paper thumbnail of Effects of intraduodenal administration of tarazepide on pancreatic secretion and duodenal EMG in neonatal calves

Regulatory peptides, Jan 30, 1998

The influence of CCK-A receptor antagonism on pancreatic exocrine secretion and duodenal EMG, and... more The influence of CCK-A receptor antagonism on pancreatic exocrine secretion and duodenal EMG, and the mechanism(s) involved in CCK-induced pancreatic secretion were studied in conscious calves. Seven 1-week-old calves were fitted with a pancreatic duct catheter, duodenal cannula and duodenal electrodes. Pancreatic exocrine secretion and duodenal EMG were studied following intraduodenal CCK-A receptor antagonist (Tarazepide), intravenous atropine, and intravenous or intraduodenal CCK-8 administrations. Tarazepide decreased duodenal electric activity, reduced interdigestive pancreatic secretion, especially protein; reduced cephalic and early postprandial (milk) induced secretion of bicarbonate and protein. Pancreatic protein secretion to intravenous CCK-8 was little affected by atropine, but was significantly reduced by Tarazepide+/-atropine; in contrast, protein secretion to intraduodenal CCK-8 was abolished by Tarazepide or atropine. We conclude that pre- and especially early postpr...

Research paper thumbnail of Elongation of the small intestine in case of experimentally induced exocrine pancreatic insufficiency in young pigs? Effect of age at pancreatic duct ligation?

Research paper thumbnail of Does the pancreas really produce much more lipase than required for fat digestion?

JOP : Journal of the pancreas, Jan 10, 2005

Thirty years ago, it was reported that a linear relationship does not exist between the amounts o... more Thirty years ago, it was reported that a linear relationship does not exist between the amounts of human pancreatic lipase secreted in chronic pancreatitis and the degree of steatorrhea, which was considered to appear only after more than 90% of the pancreatic secretory capacity had been lost. From these observations, it was generally thought that the lipolytic potential of the pancreas is much higher than required. In recent years, however, it has been noted that: 1) the level of inhibition of digestive lipases and gastrointestinal lipolysis by the lipase inhibitor orlistat were almost linearly correlated with the amount of excreted fat; 2) in minipigs with experimentally-induced pancreatic exocrine insufficiency, the amounts of enteric-coated pancreatic extracts needed for restoring fat digestion to normal levels were estimated to be much higher than those usually administered; 3) human pancreatic lipase specific activity on meal triglycerides is 3 orders of magnitude lower than t...

Research paper thumbnail of Effects of exocrine pancreatic insufficiency (EPI) and pancreatic enzyme substitution on bone mineral content of growing pigs – used as a model for children

Research paper thumbnail of Endogenous nitrogen losses (praecaecal and total) in case of exocrine pancreatic insufficiency (induced by pancreatic duct ligation) in pigs – Used as a model for humans

Research paper thumbnail of Use of hydrogen exhalation test to estimate effects of exocrine pancreatic insufficiency on fermentation of carbohydrates – Results of a study performed in healthy pigs and pancreatic duct ligated pigs – Used as a model for humans

Research paper thumbnail of The Enzyme Levels in Blood Are Not Affected by Oral Administration of a Pancreatic Enzyme Preparation (Creon 10,000) in Pancreas-Insufficient Pigs

Pancreas, 2004

After oral intake, small amounts of intact protein may be absorbed into the blood circulation. Th... more After oral intake, small amounts of intact protein may be absorbed into the blood circulation. The current study investigated whether orally administered pancreatic enzymes were absorbed from the intestine. The study included 28 pigs; 3 control pigs with intact pancreatic function and 25 pigs that were made exocrine pancreas insufficient by duct ligation (20 pigs) or total pancreatectomy (5 pigs). The pigs received a pancreatic enzyme preparation (0, 2, 4, or 8 g of Creon 10,000) together with the feed. The blood plasma was analyzed for pancreatic lipase activity with a [3H]-triolein substrate assay, while (pro)colipase and cationic trypsin(ogen) levels were measured with enzyme-linked immunosorbent assay (ELISA). Administration of Creon (0-8 g) caused no significant changes in plasma (pro)colipase or cationic trypsin(ogen) levels. Lipase activity peaks in plasma samples were found, but they did not correspond to the administration of Creon. The potential source of these plasma lipase activity peaks is discussed. The results showed no absorption into blood of pancreatic enzymes after oral administration (0, 2, 4, or 8 g of Creon mixed with 100 g of feed) to pancreas-insufficient pigs.

Research paper thumbnail of CB 1 Cannabinoid Receptor Antagonists for Treatment of Obesity and Prevention of Comorbid Metabolic Disorders

Journal of Medicinal Chemistry, 2006

ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Research paper thumbnail of NBT-PABA test to assess efficiency and kinetics of substituted proteolytic enzyme action in pancreatic duct ligated minipigs

Journal of Animal Physiology and Animal Nutrition, 2008

Research paper thumbnail of Studies on nutrient digestibilities (pre-caecal and total) in pancreatic duct-ligated pigs and the effects of enzyme substitution

Journal of Animal Physiology and Animal Nutrition, 1999

ABSTRACT

Research paper thumbnail of CONTROL OF STOMACH MOTILITY IN THE LLAMA (LA MA GUANACOE F. GLAMA

Quarterly Journal of Experimental Physiology 70, 51 -61, 1985

Manometric and electromyographic recordings of stomach motility were made in five conscious llama... more Manometric and electromyographic recordings of stomach motility were made in five conscious llamas to investigate the influence of distension of the stomach compartments, of temporary cervical vagal blockade and the influence of atropine, acetylcholine and adrenaline. The frequency of A-contractions was slowed by distension of the canal joining compartment 2 (C2) and compartment 3 (C3), or of the proximal region of C3, and either increased and/or reduced by distension of the distal region of C3 or the hind stomach. The number of B-contractions in a cycle was increased according to the degree of distension of the cranial sac of compartment 1 (C 1). B-contractions were also induced by distension of the canal or proximal region of C3 and were inhibited by distension of the distal region of C3 or the hind stomach. Contractions of C3 were not influenced by distension of Cl or C2 but were inhibited by distension of the canal, while distension within C3 caused a local excitation and an inhibition both proximal and distal to the point of stimulation. The hind stomach was only affected by local stimuli. Temporary vagal blockade abolished all contractions of C1, C2, the canal and C3, but had little effect on the motility of the hind stomach. Infusion of atropine (0-01 mg/kg), acetylcholine (7-33 1zg/kg. min) and adrenaline (0 3 Itg/kg. min) inhibited motility in all stomach compartments except the hind stomach where acetylcholine was stimulatory. it is concluded that while the hind stomach may have intrinsic motility, the contractions of Cl, C2, the canal and C3 of the llama stomach are dependent upon a vagal motor nerve supply and that the pattern of contractions observed is regulated at least partially according to the individual degree of distension of each of the stomach compartments.

Research paper thumbnail of Pattern of motility and flow of digesta in the forestomach of the Llama (Lama guanacoe f. glama

J Comp Physiol B 154, 529–533 , 1984

A study of the pattern of stomach motility was made in five conscious llamas. Motility was record... more A study of the pattern of stomach motility was made in five conscious llamas. Motility was recorded continuously by X-radiography, electromyography and/or balloons with pressure transducers, and correlated with outflow of forestomach contents measured by a thermistor. The llama forestomach showed a rhythmic pattern of contractions (motility cycle). A single cycle lasted about 82 s. Evidence is presented that each cycle comprises a single A-and numerous B-contraction sequences. Each motility cycle started with an A-sequence which began with a contraction of the canal between compartment 2 (C2) and compartment 3 (C3). A vigorous contraction of C2 followed, as the pressure in the canal fell below the baseline, then a contraction of the caudal sac of compartment 1 (C1) and another contraction of the canal occurred. The B-sequence of contractions began with a contraction of the cranial sac of C1 at the same time as the second canal contraction, followed by a weak contraction of C2 and finally a contraction of the caudal sac of C1. This B-sequence was repeated a number of times in each motility cycle. Passage of contents from C2 to C3 only occurred as the canal relaxed during the A-contraction. Continuous aborally-directed segmention and peristaltic-like movements were recorded in C3. These contractions occurred at 10 min-1 in the proximal part, and at 5 min-1 in the distal part where they were strongest. In the hind stomach mixing movements could be seen. At the border between C3 and the hind stomach, within a length of 10cm the pH fell from 6 to less than 2. No

Research paper thumbnail of Ibipinabant attenuates β-cell loss in male Zucker diabetic fatty rats independently of its effects on body weight

Diabetes, Obesity and Metabolism 14: 555 – 564,, 2012

Aim: To test the antidiabetic efficacy of ibipinabant, this new cannabinoid receptor 1 (CB1) anta... more Aim: To test the antidiabetic efficacy of ibipinabant, this new cannabinoid receptor 1 (CB1) antagonist was compared with food-restrictioninduced weight loss, rosiglitazone (4 mg/kg) and rimonabant (3 and 10 mg/kg), using parameters of glycaemic control in male Zucker diabetic fatty (ZDF) rats. Methods: Body weight, food and water intake, fasted and non-fasted glucose and insulin, glucose tolerance and glycosylated haemoglobin (HbA1c) were all assessed over the course of the 9-week study. Pancreatic insulin content and islet area were also evaluated. Results: At the end of the study, vehicle-treated ZDF rats were severely hyperglycaemic and showed signs of β-cell decline, including dramatic reductions in unfasted insulin levels. Ibipinanbant (10 mg/kg) reduced the following relative to vehicle controls: fasting glucose (−61%), glucose excursion area under the curve (AUC) in an oral glucose tolerance test (OGTT, −44%) and HbA1c (−50%). Furthermore, non-fasting insulin, islet area and islet insulin content were all increased (71, 40 and 76%, respectively) relative to vehicle controls by the end of the study. All of these effects were similar to those of rimonabant and rosiglitazone, where ibipinabant was slightly more effective than rimonabant at the lowest dose and somewhat less effective than rosiglitazone at all doses. These antidiabetic effects appear independent of weight loss because none of the parameters above were consistently improved by the comparable weight loss induced by food restriction. Conclusions: Ibipinabant may have weight loss-independent antidiabetic effects and may have the potential to attenuate β-cell loss in a model of progressive β-cell dysfunction.

Research paper thumbnail of Prececal digestibility of various sources of starch in minipigs with or without experimentally induced exocrine pancreatic insufficiency

Journal of Animal Science, 2012

Research paper thumbnail of Some cannabinoid receptor ligands and their distomers are direct-acting openers of SUR1 KATP channels

American Journal of Physiology-Endocrinology and Metabolism, 2011

Here, we examined the chronic effects of two cannabinoid receptor-1 (CB1) inverse agonists, rimon... more Here, we examined the chronic effects of two cannabinoid receptor-1 (CB1) inverse agonists, rimonabant and ibipinabant, in hyperinsulinemic Zucker rats to determine their chronic effects on insulinemia. Rimonabant and ibipinabant (10 mg·kg−1·day−1) elicited body weight-independent improvements in insulinemia and glycemia during 10 wk of chronic treatment. To elucidate the mechanism of insulin lowering, acute in vivo and in vitro studies were then performed. Surprisingly, chronic treatment was not required for insulin lowering. In acute in vivo and in vitro studies, the CB1 inverse agonists exhibited acute K channel opener (KCO; e.g., diazoxide and NN414)-like effects on glucose tolerance and glucose-stimulated insulin secretion (GSIS) with approximately fivefold better potency than diazoxide. Followup studies implied that these effects were inconsistent with a CB1-mediated mechanism. Thus effects of several CB1 agonists, inverse agonists, and distomers during GTTs or GSIS studies us...

Research paper thumbnail of {"__content__"=>"Metabolic markers of protein maldigestion after a N test meal in minipigs with pancreatic exocrine insufficiency.", "sup"=>{"__content__"=>"15"}}

American journal of physiology. Gastrointestinal and liver physiology, Feb 1, 2018

The effect of pancreatic exocrine insufficiency (PEI) on protein malabsorption is little document... more The effect of pancreatic exocrine insufficiency (PEI) on protein malabsorption is little documented, partly due to methodological barriers. We aimed to validate biomarkers of protein malabsorption using a N test meal in a minipig model of PEI. Six pancreatic duct-ligated minipigs were used as a model of PEI and four nonoperated animals as a control. All animals were equipped with an ileocecal reentrant cannula. Minipigs were given a test meal containing [N]casein. The PEI animals repeated the test three times, in the absence of any pancreatic enzymes, or after pancreatic substitution at two levels [ A or B: 7,500 or 75,000 (lipase) and 388 or 3881 (protease) FIP U]. Ileal chyme, urine, and blood were collected postprandially. Nitrogen and N were measured in digestive and metabolic pools. We obtained a gradient of ileal protein digestibility from 29 ± 11% in PEI to 89 ± 6% in the controls and a dose- dependent response of enzymes. Insulin and gastric inhibitory polypeptide secretions...

Research paper thumbnail of Glucose homeostasis dependency on acini-islet-acinar (AIA) axis communication: a new possible pathophysiological hypothesis regarding diabetes mellitus

Nutrition & diabetes, Jan 8, 2018

Studies have highlighted the existence of two intra-pancreatic axes of communication: one involve... more Studies have highlighted the existence of two intra-pancreatic axes of communication: one involved in the regulation of enzyme production by insulin-the insular-acinar axis; and another involved in the regulation of insulin release by pancreatic enzymes-the acini-insular axis. Previous studies by our laboratory show that pancreatic enzymes can affect blood glucose homeostasis and insulin secretion independently of their digestive functions, both from the gut lumen and probably from the blood. As a result we would like to introduce here the concept of acini-islet-acinar (AIA) axis communication (feedback), which could play an important role in the development of obesity and diabetes type 2. The AIA feedback links the endocrine and exocrine parts of the pancreas and emphasizes the essential role that the pancreas plays, as a single organ, in the regulation of glucose homeostasis by amylase most probably in gut epithelium and by insulin and glucagon in peripheral blood.

Research paper thumbnail of Experiments suggesting extra-digestive effects of enteral pancreatic amylase and its peptides on glucose homeostasis in a pig model

Scientific reports, Jan 17, 2017

The studies presented were designed to highlight the impact of pancreatic enzymes on glycemic con... more The studies presented were designed to highlight the impact of pancreatic enzymes on glycemic control and insulin response. Blood glucose and plasma insulin levels were monitored after intravenous, oral or direct gut glucose tolerance tests (GTT) in 6 pigs with an intact gastrointestinal tract and in 12 pigs following duodenal-jejunal bypass (DJB) surgery. In the intact pigs, pancreatic enzymes (Creon®) given orally 1 h prior to the GTT, lowered the blood glucose levels during the oral and meal GTT and reduced the plasma insulin response during the intravenous and meal GTT. In DJB pigs, blood glucose and plasma insulin levels were higher following glucose loading into the by-passed biliopancreatic limb as compared to that following glucose loading orally or into the common intestinal limb. Infusion of amylase or amylase peptides together with glucose into the biliopancreatic limb lowered blood glucose levels in DJB pigs. These preliminary data suggest new, extra-digestive, actions o...

Research paper thumbnail of The Pancreatic Duct Ligated (Mini)pig as a Model for Pancreatic Exocrine Insufficiency in Man

Pancreas, 2016

Modern therapy of pancreatic exocrine insufficiency (PEI) using pancreatic enzyme replacement the... more Modern therapy of pancreatic exocrine insufficiency (PEI) using pancreatic enzyme replacement therapy (PERT) has largely been very effective and has greatly helped in improving the nutritional status of patients with PEI and in increasing the life expectancy in cystic fibrosis. It is believed that the use of predictable large animal models could play an important role in assessing and developing new therapies. This article reviews the pancreatic duct ligated (adult) minipig as a chronic model of total PEI, with a detailed look at the influence of PEI and response to PERT on prececal compared to fecal digestibility, to directly investigate effects on protein and starch digestion and absorption. In addition, the piglet with PEI is reviewed as a model for PEI in young patients with the aim of further improving the therapy and nutritional status of young patients with cystic fibrosis.

Research paper thumbnail of Endogenous praecaecal and total tract losses of nitrogen in pancreatic duct-ligated minipigs

Http Dx Doi Org 10 1080 1745039x 2015 1009612, Feb 18, 2015

The pancreatic duct-ligated minipig (PL) is an established model of pancreatic exocrine insuffici... more The pancreatic duct-ligated minipig (PL) is an established model of pancreatic exocrine insufficiency (PEI) with a significant decrease of nutrient digestibility. This study aimed to quantify and compare endogenous losses of nitrogen (N) (ileal and faecal) in minipigs receiving an almost N-free diet. Altogether, 12 Göttingen minipigs (7 PL and 5 control animals) fitted with an re-entrant ileo-caecal fistula were used. In Study 1, ileal digesta was collected over a period of 12 h on seven consecutive days, including one 24 h collection, when animals were fed a diet containing 0.49 g N/kg dry matter (DM). In Study 2, faeces were collected for 10 consecutive days. In Group PL, the amount and DM content of ileal digesta were higher (p < 0.05), while N concentration was lower than in the Control. The ileo-caecal N flux [g/kg DM intake] was about 2.5 times higher in Group PL (5.47 ± 1.15) than in the Control (1.91 ± 0.59) (p < 0.05). The amount of faeces did not differ, but faecal N losses were higher in Group PL (p < 0.05). Endogenous faecal N losses [g N/kg DM intake] of the Control group (1.17 ± 0.72) were comparable with earlier studies, while those of Group PL were 2.6 times higher (3.09 ± 1.34). In contrast, urinary excretion of N did not differ between the Control and Group PL. In conclusion, PEI caused markedly increased endogenous N losses. Therefore, the impact of reduced digestibility of nutrients on endogenous N losses might be relevant for apparent protein digestibility rates and should be taken into account.

Research paper thumbnail of Effects of intraduodenal administration of tarazepide on pancreatic secretion and duodenal EMG in neonatal calves

Regulatory peptides, Jan 30, 1998

The influence of CCK-A receptor antagonism on pancreatic exocrine secretion and duodenal EMG, and... more The influence of CCK-A receptor antagonism on pancreatic exocrine secretion and duodenal EMG, and the mechanism(s) involved in CCK-induced pancreatic secretion were studied in conscious calves. Seven 1-week-old calves were fitted with a pancreatic duct catheter, duodenal cannula and duodenal electrodes. Pancreatic exocrine secretion and duodenal EMG were studied following intraduodenal CCK-A receptor antagonist (Tarazepide), intravenous atropine, and intravenous or intraduodenal CCK-8 administrations. Tarazepide decreased duodenal electric activity, reduced interdigestive pancreatic secretion, especially protein; reduced cephalic and early postprandial (milk) induced secretion of bicarbonate and protein. Pancreatic protein secretion to intravenous CCK-8 was little affected by atropine, but was significantly reduced by Tarazepide+/-atropine; in contrast, protein secretion to intraduodenal CCK-8 was abolished by Tarazepide or atropine. We conclude that pre- and especially early postpr...

Research paper thumbnail of Elongation of the small intestine in case of experimentally induced exocrine pancreatic insufficiency in young pigs? Effect of age at pancreatic duct ligation?

Research paper thumbnail of Does the pancreas really produce much more lipase than required for fat digestion?

JOP : Journal of the pancreas, Jan 10, 2005

Thirty years ago, it was reported that a linear relationship does not exist between the amounts o... more Thirty years ago, it was reported that a linear relationship does not exist between the amounts of human pancreatic lipase secreted in chronic pancreatitis and the degree of steatorrhea, which was considered to appear only after more than 90% of the pancreatic secretory capacity had been lost. From these observations, it was generally thought that the lipolytic potential of the pancreas is much higher than required. In recent years, however, it has been noted that: 1) the level of inhibition of digestive lipases and gastrointestinal lipolysis by the lipase inhibitor orlistat were almost linearly correlated with the amount of excreted fat; 2) in minipigs with experimentally-induced pancreatic exocrine insufficiency, the amounts of enteric-coated pancreatic extracts needed for restoring fat digestion to normal levels were estimated to be much higher than those usually administered; 3) human pancreatic lipase specific activity on meal triglycerides is 3 orders of magnitude lower than t...

Research paper thumbnail of Effects of exocrine pancreatic insufficiency (EPI) and pancreatic enzyme substitution on bone mineral content of growing pigs – used as a model for children

Research paper thumbnail of Endogenous nitrogen losses (praecaecal and total) in case of exocrine pancreatic insufficiency (induced by pancreatic duct ligation) in pigs – Used as a model for humans

Research paper thumbnail of Use of hydrogen exhalation test to estimate effects of exocrine pancreatic insufficiency on fermentation of carbohydrates – Results of a study performed in healthy pigs and pancreatic duct ligated pigs – Used as a model for humans

Research paper thumbnail of The Enzyme Levels in Blood Are Not Affected by Oral Administration of a Pancreatic Enzyme Preparation (Creon 10,000) in Pancreas-Insufficient Pigs

Pancreas, 2004

After oral intake, small amounts of intact protein may be absorbed into the blood circulation. Th... more After oral intake, small amounts of intact protein may be absorbed into the blood circulation. The current study investigated whether orally administered pancreatic enzymes were absorbed from the intestine. The study included 28 pigs; 3 control pigs with intact pancreatic function and 25 pigs that were made exocrine pancreas insufficient by duct ligation (20 pigs) or total pancreatectomy (5 pigs). The pigs received a pancreatic enzyme preparation (0, 2, 4, or 8 g of Creon 10,000) together with the feed. The blood plasma was analyzed for pancreatic lipase activity with a [3H]-triolein substrate assay, while (pro)colipase and cationic trypsin(ogen) levels were measured with enzyme-linked immunosorbent assay (ELISA). Administration of Creon (0-8 g) caused no significant changes in plasma (pro)colipase or cationic trypsin(ogen) levels. Lipase activity peaks in plasma samples were found, but they did not correspond to the administration of Creon. The potential source of these plasma lipase activity peaks is discussed. The results showed no absorption into blood of pancreatic enzymes after oral administration (0, 2, 4, or 8 g of Creon mixed with 100 g of feed) to pancreas-insufficient pigs.

Research paper thumbnail of CB 1 Cannabinoid Receptor Antagonists for Treatment of Obesity and Prevention of Comorbid Metabolic Disorders

Journal of Medicinal Chemistry, 2006

ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Research paper thumbnail of NBT-PABA test to assess efficiency and kinetics of substituted proteolytic enzyme action in pancreatic duct ligated minipigs

Journal of Animal Physiology and Animal Nutrition, 2008

Research paper thumbnail of Studies on nutrient digestibilities (pre-caecal and total) in pancreatic duct-ligated pigs and the effects of enzyme substitution

Journal of Animal Physiology and Animal Nutrition, 1999

ABSTRACT

Research paper thumbnail of Effect of Decreased Arterial Pco2 on the Pial Arteriolar Response to Adenosine

Advances in Neurology volume 20, 1978

Recent studies have demonstrated a strong dilatatory response of pial arterioles to adenosine (1,... more Recent studies have demonstrated a strong dilatatory response of pial arterioles to adenosine (1, 10). However, this response has not been tested under conditions which alter cerebrovascular resistance. The present study was undertaken to investigate the effect of lowering the arterial pCOz on adenosine-induced dilation of pial arterioles in the caL