Research Topics
Species | G F LewisSummaryAffiliation: University of Toronto Country: Canada Publications
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Publications
Mechanisms of incretin effects on plasma lipids and implications for the cardiovascular systemChangting Xiao
Toronto General Hospital, 200 Elizabeth Street, EN12 218, Toronto, Ontario, M5G 2C4, Canada
Cardiovasc Hematol Agents Med Chem 10:289-94. 2012..This review aims to summarize the evidence and potential mechanism of such agents in humans in modulating fasting and postprandial lipoprotein metabolism...- Lipid metabolismGary F Lewis
Department of Medicine and Physiology, University of Toronto, Toronto, Ontario, Canada
Curr Opin Lipidol 15:85-7. 2004 - Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetesGary F Lewis
Department of Medicine, Division of Endocrinology, University of Toronto, Canada M5G 2C4
Endocr Rev 23:201-29. 2002.... - Intestinal lipoprotein production is stimulated by an acute elevation of plasma free fatty acids in the fasting state: studies in insulin-resistant and insulin-sensitized Syrian golden hamstersGary F Lewis
Toronto General Hospital, 200 Elizabeth Street, EN11 229, Toronto, Ontario, Canada
Endocrinology 145:5006-12. 2004..With RSG treatment, basal PR is partially normalized, and they become more susceptible to the acute FFA stimulatory effect... - Intestinal lipoprotein overproduction, a newly recognized component of insulin resistance, is ameliorated by the insulin sensitizer rosiglitazone: studies in the fructose-fed Syrian golden hamsterGary F Lewis
Department of Medicine, Division of Endocrinology and Metabolism, Hospital for Sick Children, Univeristy of Toronto, Toronto, Ontario, Canada
Endocrinology 146:247-55. 2005..The data suggest that intestinal lipoprotein overproduction can be ameliorated with the insulin sensitizer rosiglitazone... - Hepatic lipase mRNA, protein, and plasma enzyme activity is increased in the insulin-resistant, fructose-fed Syrian golden hamster and is partially normalized by the insulin sensitizer rosiglitazoneGary F Lewis
Department of Medicine and Physiology, Division of Endocrinology and Metabolism, University of Toronto, Ontario, Canada
Diabetes 53:2893-900. 2004.... 
The effect of high-dose sodium salicylate on chronically elevated plasma nonesterified fatty acid-induced insulin resistance and β-cell dysfunction in overweight and obese nondiabetic menChangting Xiao
Departments of Medicine and Physiology, University of Toronto, Toronto, Ontario, Canada
Am J Physiol Endocrinol Metab 297:E1205-11. 2009..These data suggest that oral sodium salicylate at this dose impairs insulin clearance but does not ameliorate lipid-induced insulin resistance and β-cell dysfunction in overweight and obese nondiabetic men...- New insights into the regulation of HDL metabolism and reverse cholesterol transportGary F Lewis
Department of Medicine and Physiology, University of Toronto, Canada
Circ Res 96:1221-32. 2005.... - Determinants of plasma HDL concentrations and reverse cholesterol transportGary F Lewis
Department of Medicine, University of Toronto, Ontario, Canada
Curr Opin Cardiol 21:345-52. 2006..This review focuses on recent progress in our understanding of reverse cholesterol transport and the factors that determine plasma HDL cholesterol concentrations... - Are the lipid-modifying effects of fibrates mediated by alterations in plasma lipid transfer activity?Gary F Lewis
Toronto General Hospital, 200 Elizabeth Street, EN12 218, Toronto, ON, Canada M5G 2C4
Clin Sci (Lond) 111:185-7. 2006.... - Fatty acids mediate the acute extrahepatic effects of insulin on hepatic glucose production in humansG F Lewis
Department of Medicine, University of Toronto, Ontario, Canada
Diabetes 46:1111-9. 1997..This suggests that other mechanisms, most likely hepatic, dominate the acute insulin-induced suppression of glucose production... - Counterregulatory response to hypoglycemia differs according to the insulin delivery route, but does not affect glucose production in normal humansG F Lewis
Department of Medicine, University of Toronto, Ontario, Canada
J Clin Endocrinol Metab 84:1037-46. 1999..The clinical importance of these observations in diabetic subjects as they relate to route of insulin delivery (portal or peripheral) during insulin dissipation remains to be determined... - Resistance to insulin's acute direct hepatic effect in suppressing steady-state glucose production in individuals with type 2 diabetesG F Lewis
Department of Medicine, University of Toronto, Ontario, Canada
Diabetes 48:570-6. 1999..In conclusion, this is the first study in patients with type 2 diabetes to characterize insulin resistance to the acute direct suppressive effect of insulin on hepatic glucose production... - Effect of increased plasma non-esterified fatty acids (NEFAs) on arginine-stimulated insulin secretion in obese humansA Carpentier
Department of Medicine, Division of Endocrinology, University of Toronto, Toronto General Hospital, Toronto, Ontario, Canada
Diabetologia 44:1989-97. 2001..These findings suggest that the previously demonstrated NEFA-induced impairment in insulin secretory response to glucose cannot be generalized for non-glucose secretagogues... - Mechanisms of hepatic very low-density lipoprotein overproduction in insulin resistanceK Adeli
Division of Clinical Biochemistry, Department of Laboratory Medicine and Pathobiology, Hospital for Sick Children, University of Toeonto, Toronto, Ontario, Canada
Trends Cardiovasc Med 11:170-6. 2001..g., in streptozotocin-treated animals), which appears to have a different etiology and is related to a catabolic defect rather than secretory overproduction of triglyceride-rich lipoproteins... - Fasting and postprandial overproduction of intestinally derived lipoproteins in an animal model of insulin resistance. Evidence that chronic fructose feeding in the hamster is accompanied by enhanced intestinal de novo lipogenesis and ApoB48-containing liMehran Haidari
Department of Laboratory Medicine and Pathobiology, Hospital for Sick Children, University of Toronto, Toronto, Ontario M5G 1X8, Canada
J Biol Chem 277:31646-55. 2002.... - The effect of systemic versus portal insulin delivery in pancreas transplantation on insulin action and VLDL metabolismA Carpentier
Department of Medicine, University of Toronto, Toronto, Ontario, Canada
Diabetes 50:1402-13. 2001.... - Prolonged increase of plasma non-esterified fatty acids fully abolishes the stimulatory effect of 24 hours of moderate hyperglycaemia on insulin sensitivity and pancreatic beta-cell function in obese menN Leung
Department of Medicine, Division of Endocrinology and Metabolism and the Department of Physiology, University of Toronto, Toronto, Ontario, Canada
Diabetologia 47:204-13. 2004..This suggests that previous observations, showing that a prolonged increase of plasma NEFA impairs pancreatic beta-cell function, also apply to the hyperglycaemic state... - Ameliorated hepatic insulin resistance is associated with normalization of microsomal triglyceride transfer protein expression and reduction in very low density lipoprotein assembly and secretion in the fructose-fed hamsterAndre Carpentier
Department of Medicine, Division of Endocrinology and Metabolism, University Health Network, Hospital for Sick Children, University of Toronto, Toronto, Ontario M5G 2C4, Canada
J Biol Chem 277:28795-802. 2002.... - Mechanisms of HDL lowering in insulin resistant, hypertriglyceridemic states: the combined effect of HDL triglyceride enrichment and elevated hepatic lipase activityShirya Rashid
Department of Medicine, Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada
Clin Biochem 36:421-9. 2003..The present review focuses on these metabolic alterations in insulin resistant states and their important contributions to the reduction of HDL-c and HDL-apoA-I plasma concentrations... - Enhanced cellular uptake of remnant high-density lipoprotein particles: a mechanism for high-density lipoprotein lowering in insulin resistance and hypertriglyceridemiaChangting Xiao
Department of Medicine and Physiology, University of Toronto, Ontario, Canada
Circ Res 103:159-66. 2008.... - Triglyceride enrichment of HDL does not alter HDL-selective cholesteryl ester clearance in rabbitsS Rashid
Department of Medicine, Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada M5G 2C4
J Lipid Res 42:265-71. 2001..Further studies are needed to determine whether, in the presence of HL, TG enrichment of HDL alters selective HDL CE clearance... - Dissociation between the insulin-sensitizing effect of rosiglitazone and its effect on hepatic and intestinal lipoprotein productionHélène Duez
Departments of Medicine and Physiology, Toronto General Hospital, 200 Elizabeth Street, Toronto, Ontario, Canada
J Clin Endocrinol Metab 93:1722-9. 2008..The mechanism of this effect is currently not known... 
Insulin acutely inhibits intestinal lipoprotein secretion in humans in part by suppressing plasma free fatty acidsMirjana Pavlic
Division of Endocrinology and Metabolism, Department of Medicine and Physiology, University of Toronto, Toronto, Canada
Diabetes 59:580-7. 2010..Here, we investigated the effect of acute hyperinsulinemia on intestinal (and hepatic) lipoprotein production in six healthy men in the presence and absence of concomitant suppression of plasma free fatty acids (FFAs)...- Hyperinsulinemia is associated with increased production rate of intestinal apolipoprotein B-48-containing lipoproteins in humansHélène Duez
Division of Endocrinology and Metabolism, Department of Medicine, University of Toronto, Ontario, Canada
Arterioscler Thromb Vasc Biol 26:1357-63. 2006.... - Lipolytically modified triglyceride-enriched HDLs are rapidly cleared from the circulationShirya Rashid
Department of Medicine, Division of Endocrinology, University of Toronto, Canada
Arterioscler Thromb Vasc Biol 22:483-7. 2002..These data further support the important interaction between HDL TG enrichment and HL action in the pathogenesis of HDL lowering in hypertriglyceridemic states... - Triglyceride-rich lipoprotein-associated apolipoprotein C-III production is stimulated by plasma free fatty acids in humansMirjana Pavlic
Department of Medicine, University of Toronto, Canada
Arterioscler Thromb Vasc Biol 28:1660-5. 2008..The mechanism underlying that increase is not known, but because apoC-III and VLDL production are closely linked we hypothesized that FFAs may stimulate TRL apoC-III production... - Rosiglitazone improves intestinal lipoprotein overproduction in the fat-fed Syrian Golden hamster, an animal model of nutritionally-induced insulin resistanceNathalie Leung
Department of Medicine, University of Toronto, Toronto, Ont, Canada
Atherosclerosis 174:235-41. 2004..These data further support the link between insulin resistance and intestinal lipoprotein overproduction... - Portal venous and enteric exocrine drainage versus systemic venous and bladder exocrine drainage of pancreas grafts: clinical outcome of 40 consecutive transplant recipientsM S Cattral
Multiorgan Transplantation Program, The Toronto General Hospital, University Health Network, and the Departments of Surgery and Medicine, University of Toronto, Toronto, Ontario, Canada
Ann Surg 232:688-95. 2000.... - Differential effects of monounsaturated, polyunsaturated and saturated fat ingestion on glucose-stimulated insulin secretion, sensitivity and clearance in overweight and obese, non-diabetic humansC Xiao
Department of Medicine and Physiology, University of Toronto, Toronto, ON, Canada
Diabetologia 49:1371-9. 2006..PUFA ingestion resulted in an absolute reduction in insulin secretion and SFA ingestion induced insulin resistance. Failure of insulin secretion to compensate for insulin resistance implies impaired beta cell function in the SFA study... - Oral taurine but not N-acetylcysteine ameliorates NEFA-induced impairment in insulin sensitivity and beta cell function in obese and overweight, non-diabetic menC Xiao
Department of Medicine, University of Toronto, Toronto, ON, Canada
Diabetologia 51:139-46. 2008..The aim of the present study was to examine the effects of two orally administered antioxidants, N-acetylcysteine (NAC) and taurine (TAU), on lipotoxicity in humans... - Intestinal lipoprotein overproduction in insulin-resistant statesKhosrow Adeli
Molecular Structure and Function, Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
Curr Opin Lipidol 19:221-8. 2008..This article will review our current understanding of the link between insulin resistance and intestinal lipoprotein overproduction and highlight some of the key recent findings in the field... - Hepatic very low density lipoprotein-ApoB overproduction is associated with attenuated hepatic insulin signaling and overexpression of protein-tyrosine phosphatase 1B in a fructose-fed hamster model of insulin resistanceChangiz Taghibiglou
Division of Clinical Biochemistry, Department of Laboratory Medicine and Pathobiology, Hospital for Sick Children, University of Toronto, Toronto, Ontario M5G 1X8, Canada
J Biol Chem 277:793-803. 2002..Induction of hepatic insulin resistance may then contribute to reduced apoB degradation and enhanced VLDL particle assembly and secretion... - Effect of atorvastatin on high-density lipoprotein apolipoprotein A-I production and clearance in the New Zealand white rabbitShirya Rashid
Department of Medicine, Division of Endocrinology, University of Toronto, Toronto, Canada
Circulation 106:2955-60. 2002..Whether this finding results from an effect of atorvastatin on HDL particle composition or on receptors involved in circulating HDL holoparticle clearance will require further study... - Free fatty acid-mediated impairment of glucose-stimulated insulin secretion in nondiabetic Oji-Cree individuals from the Sandy Lake community of Ontario, Canada: a population at very high risk for developing type 2 diabetesAndre Carpentier
Department of Medicine, University of Sherbrooke, Sherbrooke, Quebec, Canada
Diabetes 52:1485-95. 2003..Whether this reflects an inherent resistance to lipotoxicity or an already-present lipotoxic effect in this population will require further study... - Expression of human hepatic lipase in the rabbit model preferentially enhances the clearance of triglyceride-enriched versus native high-density lipoprotein apolipoprotein A-IShirya Rashid
Department of Medicine, Division of Endocrinology, University of Toronto, Toronto, Canada
Circulation 107:3066-72. 2003.... - Sensitivity to acute insulin-mediated suppression of plasma free fatty acids is not a determinant of fasting VLDL triglyceride secretion in healthy humansAndre Carpentier
Department of Medicine, Division of Endocrinology, University of Toronto, Ontario, Canada
Diabetes 51:1867-75. 2002..The sensitivity to insulin's acute suppressive effect on plasma FFA levels during fasting is not an important determinant of postabsorptive VLDL-TG secretion in humans... - Free fatty acid-induced reduction in glucose-stimulated insulin secretion: evidence for a role of oxidative stress in vitro and in vivoAndrei I Oprescu
Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
Diabetes 56:2927-37. 2007..Our objective was to investigate the role of oxidative stress in FFA-induced decrease in beta-cell function... - Acute cannabinoid receptor type 1 (CB1R) modulation influences insulin sensitivity by an effect outside the central nervous system in miceD Song
Department of Medicine, University of Toronto, Toronto, ON, Canada
Diabetologia 54:1181-9. 2011..Here we examined the relative contributions of acute CNS and extra-CNS CB1R modulation on insulin sensitivity using pharmacological gain- and loss-of-function of CB1R in mice... - Thiazolidinediones: novel treatments for cognitive deficits in mood disorders?Roger S McIntyre
University of Toronto, Department of Psychiatry, Toronto, ON, Canada
Expert Opin Pharmacother 8:1615-28. 2007..Extant data provide the basis for formulating a hypothesis that TZDs may be salutary for cognitive deficits and several aspects of somatic health (e.g., cardiovascular disease) associated with mood disorders... - Atorvastatin induces insulin sensitization in Zucker lean and fatty ratsVictor Wong
Department of Medicine, Division of Endocrinology and Metabolism, University of Toronto, Ont, Canada; Department of Physiology, University of Toronto, Ont, Canada
Atherosclerosis 184:348-55. 2006..CONCLUSION: Atorvastatin induces insulin sensitization in Zucker lean and fatty rats. This may be a clinically important pleiotropic effect if confirmed in insulin resistant humans... - Vasopeptidase inhibitor omapatrilat induces profound insulin sensitization and increases myocardial glucose uptake in Zucker fatty rats: Studies comparing a vasopeptidase inhibitor, angiotensin-converting enzyme inhibitor, and angiotensin II type I receptChao-Hung Wang
Department of Medicine, Division of Endocrinology and Metabolism, Toronto General Hospital and University Health Network, Toronto, Ontario, Canada
Circulation 107:1923-9. 2003..This effect is greater than that of ramipril and probably occurs at least in part via stimulation of the B2 receptor. OMA has the potential for greater type 2 diabetes prevention than ACEI... - Managing psychiatric disorders with antidiabetic agents: translational research and treatment opportunitiesRoger S McIntyre
Mood Disorders Psychopharmacology Unit, University Health Network, 399 Bathurst Street Toronto, ON, M5T 2S8, Canada
Expert Opin Pharmacother 7:1305-21. 2006..Antidiabetic treatments, which maintain euglycaemia, hold promise as potent and clinically significant therapeutic interventions for several neuropsychiatric disorders... - Both intestinal and hepatic lipoprotein production are stimulated by an acute elevation of plasma free fatty acids in humansHélène Duez
Department of Medicine, Division of Endocrinology and Metabolism, University of Toronto, Toronto, Canada
Circulation 117:2369-76. 2008..Here we investigated whether short-term elevation of plasma FFAs stimulates intestinal apolipoprotein (apo) B-48- and hepatic apoB-100-containing triglyceride-rich lipoprotein (TRL) production in humans in the fed state... - Hepatic PTP-1B expression regulates the assembly and secretion of apolipoprotein B-containing lipoproteins: evidence from protein tyrosine phosphatase-1B overexpression, knockout, and RNAi studiesWei Qiu
Department of Laboratory Medicine and Pathobiology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
Diabetes 53:3057-66. 2004.... - Mechanism of intestinal lipoprotein overproduction in insulin resistant humansHélène Duez
Department of Medicine, Division of Endocrinology, University of Toronto, Toronto, Canada
Atheroscler Suppl 9:33-8. 2008.... - The mechanism of HDL lowering in hypertriglyceridemic, insulin-resistant statesShirya Rashid
Department of Medicine, Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada
J Diabetes Complications 16:24-8. 2002..Clin. Chim. Acta 286 (1999) 145; J. Clin. Invest. 103 (8) (1999) 1191.] to support this hypothesis, in the present brief review, we will focus predominantly on our own recent research in this area... - Enhancement of muscle glucose uptake by the vasopeptidase inhibitor, omapatrilat, is independent of insulin signaling and the AMP kinase pathwayVictor Wong
Department of Medicine, Division of Endocrinology and Metabolism and the Department of Physiology, University of Toronto, Toronto, Ontario, Canada
J Endocrinol 190:441-50. 2006..Future studies should examine whether hemodynamic effects of the drug, independent of insulin signaling, enhance glucose uptake in insulin-resistant skeletal muscle... - Lipid-induced beta-cell dysfunction in vivo in models of progressive beta-cell failureTracy T Goh
Department of Physiology, University of Toronto, Toronto, ON, M5S 1A8, Canada
Am J Physiol Endocrinol Metab 292:E549-60. 2007..3) This compensation is lost in diabetic rats with more marked hyperglycemia and loss of glucose sensing... - Mechanism of highly active anti-retroviral therapy-induced hyperlipidemia in HIV-infected individualsAndre Carpentier
The Department of Medicine, Division of Endocrinology, Universite de Sherbrooke, Que, Canada
Atherosclerosis 178:165-72. 2005..These changes occur concomitantly with an elevation of plasma free fatty acids but before significant change in body composition... - Deterioration in renal function associated with fibrate therapyJ Lipscombe
Division of Nephrology, University Health Network, Toronto, Canada
Clin Nephrol 55:39-44. 2001..If patients with pre-existing renal dysfunction are to receive a trial of fibrate therapy, this should be done with caution and.. - Mechanisms of the free fatty acid-induced increase in hepatic glucose productionTony K T Lam
Department of Physiology and Medicine, Medical Science Building, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada
Am J Physiol Endocrinol Metab 284:E863-73. 2003..We review recent progress in this area and try to clarify controversial issues regarding the mechanisms responsible for the FFA-induced increase in hepatic glucose production in the postabsorptive state and during hyperinsulinemia... - Acute dipeptidyl peptidase-4 inhibition rapidly enhances insulin-mediated suppression of endogenous glucose production in miceHélène Duez
Department of Medicine and Physiology, Division of Endocrinology and Metabolism, University of Toronto, Toronto, Ontario, Canada
Endocrinology 150:56-62. 2009..These findings illustrate that DPP-4 inhibition modulates glucose homeostasis through pathways distinct from those used by GLP-1R agonists in mice... - Sodium phenylbutyrate, a drug with known capacity to reduce endoplasmic reticulum stress, partially alleviates lipid-induced insulin resistance and beta-cell dysfunction in humansChangting Xiao
Department of Medicine, University of Toronto, Toronto, Ontario, Canada
Diabetes 60:918-24. 2011..Here we examined the efficacy of the chemical chaperone, sodium phenylbutyrate (PBA), a drug with known capacity to reduce ER stress in animal models and in vitro, on lipid-induced insulin resistance and β-cell dysfunction in humans... - Effects of acute hyperglucagonemia on hepatic and intestinal lipoprotein production and clearance in healthy humansChangting Xiao
Department of Medicine, Division of Endocrinology and Metabolism, University of Toronto, Toronto, Ontario, Canada
Diabetes 60:383-90. 2011..Here we examined the direct effects of glucagon on regulation of hepatic and intestinal lipoprotein metabolism in humans... - Short-term oral α-lipoic acid does not prevent lipid-induced dysregulation of glucose homeostasis in obese and overweight nondiabetic menChangting Xiao
Department of Medicine, University of Toronto, Ontario, Canada
Am J Physiol Endocrinol Metab 301:E736-41. 2011..These results indicate that ALA, administered orally at this dose for 2 wk, does not protect against lipid-induced insulin resistance in overweight and obese humans... - Gut-liver interaction in triglyceride-rich lipoprotein metabolismChangting Xiao
Toronto General Hospital, ON, Canada
Am J Physiol Endocrinol Metab 301:E429-46. 2011..This review aims to integrate recent advances in our understanding of these processes and attempts to provide insight into the factors that coordinate lipid homeostasis in these two organs in health and disease... - Overexpression of the endoplasmic reticulum 60 protein ER-60 downregulates apoB100 secretion by inducing its intracellular degradation via a nonproteasomal pathway: evidence for an ER-60-mediated and pCMB-sensitive intracellular degradative pathwayWei Qiu
Division of Clinical Biochemistry, Department of Laboratory Medicine and Pathobiology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada M5G 1X8
Biochemistry 43:4819-31. 2004..ER-60 may act directly as a protease or may be involved indirectly as a chaperone/protein factor targeting apoB100 to this nonproteasomal and pCMB-sensitive degradative pathway... - Lipid metabolismGary F Lewis
Curr Opin Lipidol 13:97-9. 2002 - Objective evidence for the reversibility of nerve injury in diabetic neuropathic cachexiaJaspreet Grewal
Diabetes Care 29:473-4. 2006 - Lipid metabolismGary F Lewis
Curr Opin Lipidol 14:103-6. 2003 - Thematic review series: patient-oriented research. What have we learned about HDL metabolism from kinetics studies in humans?Shirya Rashid
Department of Cardiology, McGill University, Montreal, Canada
J Lipid Res 47:1631-42. 2006..Here, we review the progress in our understanding of HDL metabolism derived from in vivo kinetics studies, focusing primarily on studies in humans but also reviewing key studies in animal models...