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Papers by Christopher Ramnanan

Advances in Medical Education and Practice, 2015

Background: Several medical schools have implemented programs aimed at supporting clinician-educa... more Background: Several medical schools have implemented programs aimed at supporting clinician-educators with formal mentoring, training, and experience in undergraduate medical teaching. However, consensus program design has yet to be established, and the effectiveness of these programs in terms of producing quality clinician-educator teaching remains unclear. The goal of this study was to review the literature to identify motivations and perceived barriers to clinician-educators, which in turn will improve clinician-educator training programs to better align with clinician-educator needs and concerns. Methods: Review of medical education literature using the terms "attitudes", "motivations", "physicians", "teaching", and "undergraduate medical education" resulted in identification of key themes revealing the primary motivations and barriers involved in physicians teaching undergraduate medical students. Results: A synthesis of articles revealed that physicians are primarily motivated to teach undergraduate students for intrinsic reasons. To a lesser extent, physicians are motivated to teach for extrinsic reasons, such as rewards or recognition. The key barriers deterring physicians from teaching medical students included: decreased productivity, lack of compensation, increased length of the working day, patient concerns/ethical issues, and lack of confidence in their own ability. Conclusion: Our findings suggest that optimization of clinician-educator training programs should address, amongst other factors, time management concerns, appropriate academic recognition for teaching service, and confidence in teaching ability. Addressing these issues may increase the retention of clinicians who are active and proficient in medical education.

The regulation of hepatic glucose production (HGP) by insulin is critical for the maintenance of ... more The regulation of hepatic glucose production (HGP) by insulin is critical for the maintenance of desirable blood glucose concentrations. 1 HGP reflects the sum of gluconeogenesis (the synthesis and release of glucose from non-carbohydrate precursors) and glycogenolysis (glucose released from the breakdown of hepatic glycogen). An acute rise in portal vein insulin (such as occurs in response to feeding) causes the rapid suppression of HGP derived from both gluconeogenic and glycogenolytic sources. Standard textbook teaching, based on data culled largely from experiments on isolated hepatocytes, liver slices, and perfused livers from rats, posits that the gluconeogenic pathway is inhibited by insulin via rapid and profound transcriptional regulation of the 'rate-limiting' gluconeogenic enzymes. 2-6 Recent data in rodents are in line with this dogma and in addition suggest that hyperinsulinemia in the brain is sufficient to markedly inhibit flux through the gluconeogenic pathway by downregulating gluconeogenic gene expression. 7-9 By contrast, the exquisite sensitivity of HGP to physiological hyperinsulinemia in humans and dogs in vivo is clearly explained by a profound inhibition of glycogenolytic flux, but little (if any) modification of flux through the gluconeogenic pathway. 1,10-14 The purpose of this review is to examine the ways by which insulin brings about its effects on the gluconeogenic pathway in vivo and to address discrepancies in the literature concerning sensitivity of the pathway to the hormone in the whole animal. Potential Regulatory Loci for Insulin's Effects on GNG Flux to G6P There are three sources that feed into the glucose-6-phosphate (G6P) pool within the hepatocyte: • G6P formed via glucokinase-mediated phosphorylation of glucose taken up from circulation; • G6P derived from the breakdown of glycogen; and • G6P synthesized from three-carbon precursors (lactate, glycerol and certain amino acids) via the gluconeogenic pathway (GNG flux to G6P).

Molecular and Cellular Biochemistry, Feb 1, 2010

In response to energy stress (and elevated AMP), the AMP-activated protein kinase (AMPK) coordina... more In response to energy stress (and elevated AMP), the AMP-activated protein kinase (AMPK) coordinates the restoration of energy homeostasis. We determined that AMPK is activated in a model system (desert snail Otala lactea) during a physiological state of profound metabolic rate depression (estivation) in the absence of a rise in AMP. Kinetic characterization indicated a strong increase in AMPK activity and phosphorylation in estivation, consistent with an increase in P-Ser428 LKB, an established regulator of AMPK. Accordingly, approximately 2-fold increases in AMPKalpha1 protein and activity were observed with LKB1 immunoprecipitates from estivating snails. In vitro studies determined that AMPK in crude extracts was activated in the presence of cGMP and deactivated in conditions that permitted protein phosphatase type-2A (PP2A) activity. Furthermore, AMPKalpha1 protein and activity increased in PKG immunoprecipitates from estivating tissues, suggesting a novel role for PKG in the regulation of AMPK in vivo. We evaluated several downstream targets of AMPK. Acetyl-CoA carboxylase (ACC) activity was strongly inhibited in estivation, consistent with increased P-Ser79 content, and in vitro stimulation of AMPK negated citrate's ability to stimulate ACC aggregation. Analysis of other targets revealed a strong decrease in PPARgamma-coactivator 1alpha expression in both tissues, which was related to decreased gluconeogenic protein expression in hepatic tissue, but no changes in mitochondrial biogenesis markers in muscle. We concluded that AMPK activation in O. lactea aids in facilitating the suppression of anabolic pathways, without necessarily activating ATP-generating catabolism.

Advances in Medical Education and Practice, 2015

Background: Several medical schools have implemented programs aimed at supporting clinician-educa... more Background: Several medical schools have implemented programs aimed at supporting clinician-educators with formal mentoring, training, and experience in undergraduate medical teaching. However, consensus program design has yet to be established, and the effectiveness of these programs in terms of producing quality clinician-educator teaching remains unclear. The goal of this study was to review the literature to identify motivations and perceived barriers to clinician-educators, which in turn will improve clinician-educator training programs to better align with clinician-educator needs and concerns. Methods: Review of medical education literature using the terms "attitudes", "motivations", "physicians", "teaching", and "undergraduate medical education" resulted in identification of key themes revealing the primary motivations and barriers involved in physicians teaching undergraduate medical students. Results: A synthesis of articles revealed that physicians are primarily motivated to teach undergraduate students for intrinsic reasons. To a lesser extent, physicians are motivated to teach for extrinsic reasons, such as rewards or recognition. The key barriers deterring physicians from teaching medical students included: decreased productivity, lack of compensation, increased length of the working day, patient concerns/ethical issues, and lack of confidence in their own ability. Conclusion: Our findings suggest that optimization of clinician-educator training programs should address, amongst other factors, time management concerns, appropriate academic recognition for teaching service, and confidence in teaching ability. Addressing these issues may increase the retention of clinicians who are active and proficient in medical education.

The regulation of hepatic glucose production (HGP) by insulin is critical for the maintenance of ... more The regulation of hepatic glucose production (HGP) by insulin is critical for the maintenance of desirable blood glucose concentrations. 1 HGP reflects the sum of gluconeogenesis (the synthesis and release of glucose from non-carbohydrate precursors) and glycogenolysis (glucose released from the breakdown of hepatic glycogen). An acute rise in portal vein insulin (such as occurs in response to feeding) causes the rapid suppression of HGP derived from both gluconeogenic and glycogenolytic sources. Standard textbook teaching, based on data culled largely from experiments on isolated hepatocytes, liver slices, and perfused livers from rats, posits that the gluconeogenic pathway is inhibited by insulin via rapid and profound transcriptional regulation of the 'rate-limiting' gluconeogenic enzymes. 2-6 Recent data in rodents are in line with this dogma and in addition suggest that hyperinsulinemia in the brain is sufficient to markedly inhibit flux through the gluconeogenic pathway by downregulating gluconeogenic gene expression. 7-9 By contrast, the exquisite sensitivity of HGP to physiological hyperinsulinemia in humans and dogs in vivo is clearly explained by a profound inhibition of glycogenolytic flux, but little (if any) modification of flux through the gluconeogenic pathway. 1,10-14 The purpose of this review is to examine the ways by which insulin brings about its effects on the gluconeogenic pathway in vivo and to address discrepancies in the literature concerning sensitivity of the pathway to the hormone in the whole animal. Potential Regulatory Loci for Insulin's Effects on GNG Flux to G6P There are three sources that feed into the glucose-6-phosphate (G6P) pool within the hepatocyte: • G6P formed via glucokinase-mediated phosphorylation of glucose taken up from circulation; • G6P derived from the breakdown of glycogen; and • G6P synthesized from three-carbon precursors (lactate, glycerol and certain amino acids) via the gluconeogenic pathway (GNG flux to G6P).

Molecular and Cellular Biochemistry, Feb 1, 2010

In response to energy stress (and elevated AMP), the AMP-activated protein kinase (AMPK) coordina... more In response to energy stress (and elevated AMP), the AMP-activated protein kinase (AMPK) coordinates the restoration of energy homeostasis. We determined that AMPK is activated in a model system (desert snail Otala lactea) during a physiological state of profound metabolic rate depression (estivation) in the absence of a rise in AMP. Kinetic characterization indicated a strong increase in AMPK activity and phosphorylation in estivation, consistent with an increase in P-Ser428 LKB, an established regulator of AMPK. Accordingly, approximately 2-fold increases in AMPKalpha1 protein and activity were observed with LKB1 immunoprecipitates from estivating snails. In vitro studies determined that AMPK in crude extracts was activated in the presence of cGMP and deactivated in conditions that permitted protein phosphatase type-2A (PP2A) activity. Furthermore, AMPKalpha1 protein and activity increased in PKG immunoprecipitates from estivating tissues, suggesting a novel role for PKG in the regulation of AMPK in vivo. We evaluated several downstream targets of AMPK. Acetyl-CoA carboxylase (ACC) activity was strongly inhibited in estivation, consistent with increased P-Ser79 content, and in vitro stimulation of AMPK negated citrate's ability to stimulate ACC aggregation. Analysis of other targets revealed a strong decrease in PPARgamma-coactivator 1alpha expression in both tissues, which was related to decreased gluconeogenic protein expression in hepatic tissue, but no changes in mitochondrial biogenesis markers in muscle. We concluded that AMPK activation in O. lactea aids in facilitating the suppression of anabolic pathways, without necessarily activating ATP-generating catabolism.