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Polonsky, Kenneth S.

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overview	My laboratory is interested in the role of abnormal insulin secretion in the pathogenesis of type 2 diabetes. We are currently using mouse models of diabetes to define the mechanisms of ß-cell dysfunction. Pancreatic ß-cell death is a very important mechanism contributing to reduced insulin secretion in diabetes. Using Pdx1 deficiency as the experimental model we have determined that all three forms of programmed cell death autophagy, apoptosis and programmed necrosis all contribute to the loss of beta cell mass. We are currently exploring novel approaches to interrupting these pathways. These studies have focused on the role of the BH3-only molecules Puma and Bim in mediating pancreatic ß-cell death. We have demonstrated that reducing expression of Puma and Bim reduces apoptosis of the pancreatic ß-cell in different diabetes models leading to an enhancement of insulin secretion, an increase in ß-cell mass and a lowering of blood glucose.

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overview

My laboratory is interested in the role of abnormal insulin secretion in the pathogenesis of type 2 diabetes. We are currently using mouse models of diabetes to define the mechanisms of ß-cell dysfunction. Pancreatic ß-cell death is a very important mechanism contributing to reduced insulin secretion in diabetes. Using Pdx1 deficiency as the experimental model we have determined that all three forms of programmed cell death autophagy, apoptosis and programmed necrosis all contribute to the loss of beta cell mass. We are currently exploring novel approaches to interrupting these pathways. These studies have focused on the role of the BH3-only molecules Puma and Bim in mediating pancreatic ß-cell death. We have demonstrated that reducing expression of Puma and Bim reduces apoptosis of the pancreatic ß-cell in different diabetes models leading to an enhancement of insulin secretion, an increase in ß-cell mass and a lowering of blood glucose.

One or more keywords matched the following items that are connected to Polonsky, Kenneth S.

Item Type	Name
Concept	Diabetes Mellitus, Experimental
Concept	Diabetes Mellitus, Type 1
Concept	Diabetes Mellitus, Type 2
Concept	Diabetes, Gestational
Concept	Diabetes Mellitus
Academic Article	Preservation of insulin secretory responses to P2 purinoceptor agonists in Zucker diabetic fatty rats.
Academic Article	Glucokinase mutations, insulin secretion, and diabetes mellitus.
Academic Article	Seminars in Medicine of the Beth Israel Hospital, Boston. Non-insulin-dependent diabetes mellitus - a genetically programmed failure of the beta cell to compensate for insulin resistance.
Academic Article	Plasma insulin, C-peptide, and proinsulin concentrations in obese and nonobese individuals with varying degrees of glucose tolerance.
Academic Article	Clinical phenotypes, insulin secretion, and insulin sensitivity in kindreds with maternally inherited diabetes and deafness due to mitochondrial tRNALeu(UUR) gene mutation.
Academic Article	Abnormalities of insulin pulsatility and glucose oscillations during meals in obese noninsulin-dependent diabetic patients: effects of weight reduction.
Academic Article	Report of the American Diabetes Association's Task Force on standardization of the insulin assay.
Academic Article	NIDDM is associated with loss of pancreatic beta-cell L-type Ca2+ channel activity.
Academic Article	Oscillatory insulin secretion after pancreas transplant.
Academic Article	Rat inwardly rectifying potassium channel Kir6.2: cloning electrophysiological characterization, and decreased expression in pancreatic islets of male Zucker diabetic fatty rats.
Academic Article	Elevated plasma glucose 2 h postchallenge predicts defects in beta-cell function.
Academic Article	Mutations in the hepatocyte nuclear factor-1alpha gene in maturity-onset diabetes of the young (MODY3)
Academic Article	Basal and glucagon-stimulated plasma C-peptide concentrations in healthy dogs, dogs with diabetes mellitus, and dogs with hyperadrenocorticism.
Academic Article	Changes in pancreatic islet glucokinase and hexokinase activities with increasing age, obesity, and the onset of diabetes.
Academic Article	Diminished insulin and glucagon secretory responses to arginine in nondiabetic subjects with a mutation in the hepatocyte nuclear factor-4alpha/MODY1 gene.
Academic Article	Altered insulin secretory responses to glucose in diabetic and nondiabetic subjects with mutations in the diabetes susceptibility gene MODY3 on chromosome 12.
Academic Article	Low mitochondrial glycerol phosphate dehydrogenase and pyruvate carboxylase in pancreatic islets of Zucker diabetic fatty rats.
Academic Article	Prevention of hyperglycemia in the Zucker diabetic fatty rat by treatment with metformin or troglitazone.
Academic Article	Maturity onset diabetes of the young (MODY).
Academic Article	Alternative insulin delivery systems: how demanding should the patient be?
Academic Article	Metabolic effects of troglitazone monotherapy in type 2 diabetes mellitus. A randomized, double-blind, placebo-controlled trial.
Academic Article	Free fatty acids impair hepatic insulin extraction in vivo.
Academic Article	Interactions between insulin resistance and insulin secretion in the development of glucose intolerance.
Academic Article	Role of apoptosis in failure of beta-cell mass compensation for insulin resistance and beta-cell defects in the male Zucker diabetic fatty rat.
Academic Article	Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus.
Academic Article	The pancreatic beta cell heats up: UCP2 and insulin secretion in diabetes.
Academic Article	Dysregulation of insulin secretion in children with congenital hyperinsulinism due to sulfonylurea receptor mutations.
Academic Article	Glucagon-like peptide 1 improves the ability of the beta-cell to sense and respond to glucose in subjects with impaired glucose tolerance.
Academic Article	Increased beta-cell proliferation and reduced mass before diabetes onset in the nonobese diabetic mouse.
Academic Article	Failure of physiological plasma glucose excursions to entrain high-frequency pulsatile insulin secretion in type 2 diabetes.
Academic Article	Evolution of beta-cell dysfunction in impaired glucose tolerance and diabetes.
Academic Article	Abnormalities in the ultradian oscillations of insulin secretion and glucose levels in type 2 (non-insulin-dependent) diabetic patients.
Academic Article	Dynamics of insulin secretion in obesity and diabetes.
Academic Article	Glucagon-like peptide-1 stimulates insulin secretion by a Ca2+-independent mechanism in Zucker diabetic fatty rat islets of Langerhans.
Academic Article	Roles of circadian rhythmicity and sleep in human glucose regulation.
Academic Article	Insulin production: from gene to granule.
Academic Article	Defective insulin secretion in hepatocyte nuclear factor 1alpha-deficient mice.
Academic Article	Estimation of insulin secretion rates from C-peptide levels. Comparison of individual and standard kinetic parameters for C-peptide clearance.
Academic Article	Low acute insulin secretory responses in adult offspring of people with early onset type 2 diabetes.
Academic Article	Regulation of pancreatic beta-cell growth and survival by the serine/threonine protein kinase Akt1/PKBalpha.
Academic Article	Temporal profiles and clinical significance of pulsatile insulin secretion.
Academic Article	Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young.
Academic Article	Adaptation to hyperglycemia enhances insulin secretion in glucokinase mutant mice.
Academic Article	Hypoglycemic thresholds for cognitive dysfunction in IDDM.
Academic Article	Insulin release in impaired glucose tolerance: oral minimal model predicts normal sensitivity to glucose but defective response times.
Academic Article	Insulin secretory responses to rising and falling glucose concentrations are delayed in subjects with impaired glucose tolerance.
Academic Article	Calpains play a role in insulin secretion and action.
Academic Article	Diabetes mellitus and genetically programmed defects in beta-cell function.
Academic Article	Oral glucose tolerance test minimal model indexes of beta-cell function and insulin sensitivity.
Academic Article	Antidiabetic effects of Panax ginseng berry extract and the identification of an effective component.
Academic Article	Ginseng berry reduces blood glucose and body weight in db/db mice.
Academic Article	Recruitment of bone marrow-derived endothelial cells to sites of pancreatic beta-cell injury.
Academic Article	C-peptide is the appropriate outcome measure for type 1 diabetes clinical trials to preserve beta-cell function: report of an ADA workshop, 21-22 October 2001.
Academic Article	Fasting hypertriglyceridemia in noninsulin-dependent diabetes mellitus is an important predictor of postprandial lipid and lipoprotein abnormalities.
Academic Article	Visualizing superoxide production in normal and diabetic rat islets of Langerhans.
Academic Article	Defective insulin secretion and increased susceptibility to experimental diabetes are induced by reduced Akt activity in pancreatic islet beta cells.
Academic Article	Nocturnal elevation of glucose levels during fasting in noninsulin-dependent diabetes.
Academic Article	Rosiglitazone reduces glucose-stimulated insulin secretion rate and increases insulin clearance in nondiabetic, insulin-resistant individuals.
Academic Article	Reduced beta-cell mass and altered glucose sensing impair insulin-secretory function in betaIRKO mice.
Academic Article	Effects of weight loss and reduced hyperglycemia on the kinetics of insulin secretion in obese non-insulin dependent diabetes mellitus.
Academic Article	Effect of temporal distribution of calories on diurnal patterns of glucose levels and insulin secretion in NIDDM.
Academic Article	Diabetic pancreatic beta cells ARNT all they should be.
Academic Article	Does tight glucose control enhance brain sensitivity to low glucose?
Academic Article	Postprandial triglyceride response in type 1 (insulin-dependent) diabetes mellitus is not altered by short-term deterioration in glycaemic control or level of postprandial insulin replacement.
Academic Article	Hypoglycemia due to surreptitious injection of insulin. Identification of insulin species by high-performance liquid chromatography.
Academic Article	Retinol-binding protein 4, insulin resistance, and type 2 diabetes.
Academic Article	Change in hexose distribution volume and fractional utilization of [18F]-2-deoxy-2-fluoro-D-glucose in brain during acute hypoglycemia in humans.
Academic Article	Sustained expression of hepatocyte nuclear factor-6 leads to loss of pancreatic beta-cells by apoptosis.
Academic Article	Role of HNF-1alpha in regulating the expression of genes involved in cellular growth and proliferation in pancreatic beta-cells.
Academic Article	Kir6.2 variant E23K increases ATP-sensitive K+ channel activity and is associated with impaired insulin release and enhanced insulin sensitivity in adults with normal glucose tolerance.
Academic Article	A significant role for histocompatibility in human islet transplantation.
Academic Article	Two-hour seven-sample oral glucose tolerance test and meal protocol: minimal model assessment of beta-cell responsivity and insulin sensitivity in nondiabetic individuals.
Academic Article	Variation in the perilipin gene (PLIN) affects glucose and lipid metabolism in non-Hispanic white women with and without polycystic ovary syndrome.
Academic Article	Suppressed insulin signaling and increased apoptosis in CD38-null islets.
Academic Article	Loss of Nix in Pdx1-deficient mice prevents apoptotic and necrotic ß cell death and diabetes.
Academic Article	Pattern of postprandial carbohydrate metabolism and effects of portal and peripheral insulin delivery.
Academic Article	Weight loss therapy improves pancreatic endocrine function in obese older adults.
Academic Article	Insulin signaling in alpha cells modulates glucagon secretion in vivo.
Academic Article	Glyburide enhances the responsiveness of the beta-cell to glucose but does not correct the abnormal patterns of insulin secretion in noninsulin-dependent diabetes mellitus.
Academic Article	TCF7L2 variant rs7903146 affects the risk of type 2 diabetes by modulating incretin action.
Academic Article	Xenin-25 amplifies GIP-mediated insulin secretion in humans with normal and impaired glucose tolerance but not type 2 diabetes.
Academic Article	Introduction of Arthur H. Rubenstein.
Academic Article	Reduction in portal vein blood flow by somatostatin.
Academic Article	The limitations to and valid use of C-peptide as a marker of the secretion of insulin.
Academic Article	Carboxypeptidase E mediates palmitate-induced beta-cell ER stress and apoptosis.
Academic Article	Ingestion of a mixed meal does not affect the metabolic clearance rate of biosynthetic human C-peptide.
Academic Article	Insulin and glucagon breakthrough of somatostatin suppression: importance of portal vein hormone measurements.
Academic Article	Evidence for the presence of somatostatin 28 in plasma.
Academic Article	Insulin secretory defects in polycystic ovary syndrome. Relationship to insulin sensitivity and family history of non-insulin-dependent diabetes mellitus.
Academic Article	Compensation in pancreatic beta-cell function in subjects with glucokinase mutations.
Academic Article	Pdx1 and other factors that regulate pancreatic beta-cell survival.
Academic Article	Moderate effect of duodenal-jejunal bypass surgery on glucose homeostasis in patients with type 2 diabetes.
Academic Article	Reevaluation of urine C-peptide as measure of insulin secretion.
Academic Article	Abnormal patterns of insulin secretion in non-insulin-dependent diabetes mellitus.
Academic Article	Mutant insulin syndrome: identification of two families with [LeuA3]insulin and determination of its biological activity.
Academic Article	Effect of glyburide on beta cell responsiveness to glucose in non-insulin-dependent diabetes mellitus.
Academic Article	The metabolic effects of biosynthetic human proinsulin in individuals with type I diabetes.
Academic Article	The effects of biosynthetic human proinsulin on carbohydrate metabolism.
Academic Article	Aldose reductase inhibition improves nerve conduction velocity in diabetic patients.
Academic Article	Natural history of multiple intrahepatic canine islet allografts during and following administration of cyclosporine.
Academic Article	Defects in insulin secretion and action in women with a history of gestational diabetes.
Academic Article	A new method for comparing portal and peripheral venous insulin delivery in humans: tolbutamide versus insulin infusion.
Academic Article	Insulin secretion and clearance. Comparison after oral and intravenous glucose.
Academic Article	Variable deterioration in cortical function during insulin-induced hypoglycemia.
Academic Article	Evolution of beta-cell dysfunction in the male Zucker diabetic fatty rat.
Academic Article	Hepatic extraction of plasma immunoreactive glucagon components. Predilection for 3500-dalton glucagon metabolism by the liver.
Academic Article	Alterations in the patterns of insulin secretion before and after diagnosis of IDDM.
Academic Article	Calculated pattern of intraportal insulin appearance without independent assessment of C-peptide kinetics.
Academic Article	Measurement of proinsulin and intermediates. Validation of immunoassay methods by high-performance liquid chromatography.
Academic Article	Prevention of diabetes does not completely prevent insulin secretory defects in the ZDF rat.
Academic Article	Expression of calcium channel mRNAs in rat pancreatic islets and downregulation after glucose infusion.
Academic Article	Prior feeding alters the response to the 50-g glucose challenge test in pregnancy. The Staub-Traugott effect revisited.
Academic Article	Lack of glucagon response to hypoglycemia in type I diabetics after long-term optimal therapy with a continuous subcutaneous insulin infusion pump.
Academic Article	Insulin secretion in insulin-resistant women with a history of gestational diabetes.
Academic Article	Maturity-onset diabetes of the young.
Academic Article	Targeting cyclophilin D and the mitochondrial permeability transition enhances beta-cell survival and prevents diabetes in Pdx1 deficiency.
Academic Article	Insulin secretory profiles and C-peptide clearance kinetics at 6 months and 2 years after kidney-pancreas transplantation.
Academic Article	Long-term follow-up of canine segmental pancreatic autografts.
Academic Article	The past 200 years in diabetes.
Academic Article	The effect of biosynthetic human proinsulin on the hepatic response to glucagon in insulin-deficient diabetes.
Academic Article	Familial hyperinsulinemia due to a structurally abnormal insulin. Definition of an emerging new clinical syndrome.
Academic Article	Glucose counterregulation in patients after pancreatectomy. Comparison with other clinical forms of diabetes.
Academic Article	Relation of counterregulatory responses to hypoglycemia in type I diabetics.
Academic Article	Cloning of rat KATP-2 channel and decreased expression in pancreatic islets of male Zucker diabetic fatty rats.
Academic Article	Lilly Lecture 1994. The beta-cell in diabetes: from molecular genetics to clinical research.
Academic Article	Alterations in immunoreactive proinsulin and insulin clearance induced by weight loss in NIDDM.
Academic Article	Alterations in pulsatile insulin secretion in the Zucker diabetic fatty rat.
Academic Article	Glucagon does not increase plasma free fatty acid and glycerol concentrations in patients with noninsulin-dependent diabetes mellitus.
Academic Article	Basal insulin hypersecretion in insulin-resistant Zucker diabetic and Zucker fatty rats: role of enhanced fuel metabolism.
Academic Article	Loss of HNF-1alpha function in mice leads to abnormal expression of genes involved in pancreatic islet development and metabolism.
Academic Article	Diagnosis of acromegaly in a patient with type 1 diabetes mellitus.
Academic Article	Organ alchemy: producing insulin in the liver.
Academic Article	Portal vein thrombosis complicating islet transplantation in a recipient with the Factor V Leiden mutation.
Academic Article	Abnormal insulin secretion, not insulin resistance, is the genetic or primary defect of MODY in the RW pedigree.
Academic Article	International trial of the Edmonton protocol for islet transplantation.
Academic Article	Hypoglycemic thresholds for cognitive dysfunction in humans.
Academic Article	Effects of aging on insulin secretion.
Academic Article	Ginseng and ginsenoside Re do not improve ß-cell function or insulin sensitivity in overweight and obese subjects with impaired glucose tolerance or diabetes.
Academic Article	Reduction of insulin clearance during hyperglycemic clamp. Dose-response study in normal humans.
Academic Article	Use of biosynthetic human C-peptide in the measurement of insulin secretion rates in normal volunteers and type I diabetic patients.
Academic Article	Current approaches to measurement of insulin secretion.
Academic Article	C-peptide as a measure of the secretion and hepatic extraction of insulin. Pitfalls and limitations.
Academic Article	Altered insulin secretory responses to glucose in subjects with a mutation in the MODY1 gene on chromosome 20.
Academic Article	Relative effects of calorie restriction and weight loss in noninsulin-dependent diabetes mellitus.
Academic Article	Lack of control by glucose of ultradian insulin secretory oscillations in impaired glucose tolerance and in non-insulin-dependent diabetes mellitus.
Award or Honor Receipt	Outstanding Scientific Achievement Award of the American Diabetes Association (Lilly Award)
Academic Article	Role of BH3-only molecules Bim and Puma in ß-cell death in Pdx1 deficiency.
Academic Article	Xenin-25 delays gastric emptying and reduces postprandial glucose levels in humans with and without type 2 diabetes.
Academic Article	ß-cell failure in type 2 diabetes: postulated mechanisms and prospects for prevention and treatment.
Academic Article	ß-cell failure in type 2 diabetes: postulated mechanisms and prospects for prevention and treatment.
Academic Article	BH3-only molecule Bim mediates ß-cell death in IRS2 deficiency.
Academic Article	Donald F. Steiner, MD, 1930-2014: pioneering diabetes researcher.
Academic Article	Pancreatic ß-Cell Death due to Pdx-1 Deficiency Requires Multi-BH Domain Protein Bax but Not Bak.
Academic Article	35th Annual Meeting of the European Association for the Study of Diabetes : Brussels, Belgium, 28 September-2 October 1999.

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Diabetes