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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 TypeName
Concept Insulin
Concept Insulin-Like Growth Factor II
Concept Insulin Infusion Systems
Concept Insulin-Like Growth Factor I
Concept Insulin Antibodies
Concept Receptor, Insulin
Concept Insulin Resistance
Concept Insulin-Like Growth Factor Binding Protein 3
Concept Insulin-Secreting Cells
Concept Insulin Receptor Substrate Proteins
Academic Article Preservation of insulin secretory responses to P2 purinoceptor agonists in Zucker diabetic fatty rats.
Academic Article Defects in beta-cell function in functional ovarian hyperandrogenism.
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 Ultradian oscillations of leptin secretion in humans.
Academic Article Alterations in the kinetics of C-peptide and insulin secretion in hyperthyroidism.
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 Effects of metformin on insulin secretion, insulin action, and ovarian steroidogenesis in women with polycystic ovary syndrome.
Academic Article Report of the American Diabetes Association's Task Force on standardization of the insulin assay.
Academic Article Analytical problems in detecting rapid insulin secretory pulses in normal humans.
Academic Article Oscillatory insulin secretion after pancreas transplant.
Academic Article Effects of morning cortisol elevation on insulin secretion and glucose regulation in humans.
Academic Article Effects of aging on glucose regulation during wakefulness and sleep.
Academic Article Elevated plasma glucose 2 h postchallenge predicts defects in beta-cell function.
Academic Article Alterations in the ultradian oscillations of insulin secretion and plasma glucose in aging.
Academic Article Insulin acutely suppresses glucose production by both peripheral and hepatic effects in normal dogs.
Academic Article Alterations in the glucose-stimulated insulin secretory dose-response curve and in insulin clearance in nondiabetic insulin-resistant individuals.
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 Troglitazone improves defects in insulin action, insulin secretion, ovarian steroidogenesis, and fibrinolysis in women with polycystic ovary syndrome.
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 Diurnal variations in cardiovascular function and glucose regulation in normotensive humans.
Academic Article Evidence that insulin can directly inhibit hepatic glucose production.
Academic Article Late post-prandial hypoglycaemia as the sole presenting feature of secreting pancreatic beta-cell adenoma in a subtotally gastrectomized patient.
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 Circadian modulation of glucose and insulin responses to meals: relationship to cortisol rhythm.
Academic Article Interactions between insulin resistance and insulin secretion in the development of glucose intolerance.
Academic Article Quantitative indexes of beta-cell function during graded up&down glucose infusion from C-peptide minimal models.
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 Role of basal triglyceride and high density lipoprotein in determination of postprandial lipid and lipoprotein responses.
Academic Article Effects of insulin mediated plasma glucose changes on brain function. Implications from experimental and derived data.
Academic Article The pancreatic beta cell heats up: UCP2 and insulin secretion in diabetes.
Academic Article GLP-1-induced alterations in the glucose-stimulated insulin secretory dose-response curve.
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 Apoptosis in insulin-secreting cells. Evidence for the role of intracellular Ca2+ stores and arachidonic acid metabolism.
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 Insulin production: from gene to granule.
Academic Article A practical approach to fasting hypoglycemia.
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 Temporal profiles and clinical significance of pulsatile insulin secretion.
Academic Article Defective pancreatic beta-cell glycolytic signaling in hepatocyte nuclear factor-1alpha-deficient mice.
Academic Article Adaptation to hyperglycemia enhances insulin secretion in glucokinase mutant mice.
Academic Article Hypoglycemic thresholds for cognitive dysfunction in IDDM.
Academic Article Overexpression of Bcl-x(L) in beta-cells prevents cell death but impairs mitochondrial signal for insulin secretion.
Academic Article Roles of insulin resistance and obesity in regulation of plasma insulin concentrations.
Academic Article Insulin release in impaired glucose tolerance: oral minimal model predicts normal sensitivity to glucose but defective response times.
Academic Article A novel point mutation in the human insulin gene giving rise to hyperproinsulinemia (proinsulin Kyoto).
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 Modulation of glucose regulation and insulin secretion by circadian rhythmicity and sleep.
Academic Article Increased islet apoptosis in Pdx1+/- mice.
Academic Article A 48-hour exposure of pancreatic islets to calpain inhibitors impairs mitochondrial fuel metabolism and the exocytosis of insulin.
Academic Article Ryanodine receptors in human pancreatic beta cells: localization and effects on insulin secretion.
Academic Article Persistence of oscillatory insulin secretion in denervated islet cell autografts.
Academic Article Impaired beta-cell compensation to dexamethasone-induced hyperglycemia in women with polycystic ovary syndrome.
Academic Article Entrainment of pulsatile insulin secretion by oscillatory glucose infusion.
Academic Article Fasting hypertriglyceridemia in noninsulin-dependent diabetes mellitus is an important predictor of postprandial lipid and lipoprotein abnormalities.
Academic Article Defective insulin secretion and increased susceptibility to experimental diabetes are induced by reduced Akt activity in pancreatic islet beta cells.
Academic Article Reduced expression of the insulin receptor in mouse insulinoma (MIN6) cells reveals multiple roles of insulin signaling in gene expression, proliferation, insulin content, and secretion.
Academic Article Nocturnal elevation of glucose levels during fasting in noninsulin-dependent diabetes.
Academic Article Insulin sensitivity by oral glucose minimal models: validation against clamp.
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 The effect of a time delay on the characteristics of the canine glucoregulatory system.
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 Tumor hypoglycemia: relationship to high molecular weight insulin-like growth factor-II.
Academic Article Hypoglycemic potency and metabolic clearance rate of intravenously administered human proinsulin and metabolites.
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 Computer model for mechanisms underlying ultradian oscillations of insulin and glucose.
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 In vivo pulsatility of pancreatic islet peptides.
Academic Article Ginsenoside Re rapidly reverses insulin resistance in muscles of high-fat diet fed rats.
Academic Article Quantitative study of insulin secretion and clearance in normal and obese subjects.
Academic Article Twenty-four-hour profiles and pulsatile patterns of insulin secretion in normal and obese subjects.
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 Insulin Wakayama: familial mutant insulin syndrome in Japan.
Academic Article Insulin and glucagon breakthrough of somatostatin suppression: importance of portal vein hormone measurements.
Academic Article Responses of somatostatin components to oral glucose in human 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 Abnormal temporal patterns of glucose tolerance in obesity: relationship to sleep-related growth hormone secretion and circadian cortisol rhythmicity.
Academic Article Compensation in pancreatic beta-cell function in subjects with glucokinase mutations.
Academic Article Quantitative evaluation of the effect of low-intensity exercise on insulin secretion in man.
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 Ca2+ controls slow NAD(P)H oscillations in glucose-stimulated mouse pancreatic islets.
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 Peripheral insulin parallels changes in insulin secretion more closely than C-peptide after bolus intravenous glucose administration.
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 The measurement and validation of the nonsteady-state rates of C-peptide appearance in the dog.
Academic Article A familial glucagonoma syndrome: genetic, clinical and biochemical features.
Academic Article Insulin secretion and clearance. Comparison after oral and intravenous glucose.
Academic Article Calculation of the systemic delivery rate of insulin in normal man.
Academic Article Variable deterioration in cortical function during insulin-induced hypoglycemia.
Academic Article Differences in the hepatic and renal extraction of insulin and glucagon in the dog: evidence for saturability of insulin metabolism.
Academic Article Evolution of beta-cell dysfunction in the male Zucker diabetic fatty rat.
Academic Article Pancreatic hormone profiles and metabolism posthepatectomy in the dog. Evidence for a hepatotrophic role of insulin, glucagon, and pancreatic polypeptide.
Academic Article Insulin protects islets from apoptosis via Pdx1 and specific changes in the human islet proteome.
Academic Article Surface receptors for pancreatic hormones in dog and rat hepatocytes: qualitative and quantitative differences in hormone-target cell interactions.
Academic Article Alterations in the patterns of insulin secretion before and after diagnosis of IDDM.
Academic Article C-peptide and insulin secretion. Relationship between peripheral concentrations of C-peptide and insulin and their secretion rates in the dog.
Academic Article Calculated pattern of intraportal insulin appearance without independent assessment of C-peptide kinetics.
Academic Article Lack of effect of high-dose biosynthetic human C-peptide on pancreatic hormone release in normal subjects.
Academic Article Insulin secretion and clearance during low-dose graded glucose infusion.
Academic Article Oscillations in insulin secretion during constant glucose infusion in normal man: relationship to changes in plasma glucose.
Academic Article Brief report: impaired processing of prohormones associated with abnormalities of glucose homeostasis and adrenal function.
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 Targeted ablation of glucose-dependent insulinotropic polypeptide-producing cells in transgenic mice reduces obesity and insulin resistance induced by a high fat diet.
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 Hepatic metabolism of glucagon in the dog: contribution of the liver to overall metabolic disposal of glucagon.
Academic Article Insulin secretion in insulin-resistant women with a history of gestational diabetes.
Academic Article Maturity-onset diabetes of the young.
Academic Article Autophagy regulates pancreatic beta cell death in response to Pdx1 deficiency and nutrient deprivation.
Academic Article Xenin-25 potentiates glucose-dependent insulinotropic polypeptide action via a novel cholinergic relay mechanism.
Academic Article Targeting cyclophilin D and the mitochondrial permeability transition enhances beta-cell survival and prevents diabetes in Pdx1 deficiency.
Academic Article Differential effects of glucose stimulation upon rapid pulses and ultradian oscillations of insulin secretion.
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 Natural history of intrahepatic canine islet cell autografts.
Academic Article Dose-dependent effects of oral and intravenous glucose on insulin secretion and clearance in normal humans.
Academic Article The effect of biosynthetic human proinsulin on the hepatic response to glucagon in insulin-deficient diabetes.
Academic Article Metabolism of C-peptide in the dog. In vivo demonstration of the absence of hepatic extraction.
Academic Article Human insulin B24 (Phe----Ser). Secretion and metabolic clearance of the abnormal insulin in man and in a dog model.
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 A novel point mutation in the insulin gene giving rise to hyperproinsulinemia.
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 Reduced levels of messenger ribonucleic acid for calcium channel, glucose transporter-2, and glucokinase are associated with alterations in insulin secretion in fasted rats.
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 Metabolic effects of short-term elevations of plasma cortisol are more pronounced in the evening than in the morning.
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 Small-intestinal dysfunction accompanies the complex endocrinopathy of human proprotein convertase 1 deficiency.
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 Impaired insulin secretion in transgenic mice over-expressing calpastatin in pancreatic ß-cells.
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 Lack of direct inhibition of insulin secretion by exogenous insulin in the canine pancreas.
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 Glucose ingestion in dogs alters the hepatic extraction of insulin. In vivo evidence for a relationship between biologic action and extraction of insulin.
Academic Article 24-hour glucose profiles during continuous or oscillatory insulin infusion. Demonstration of the functional significance of ultradian insulin oscillations.
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.
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 Pancreatic ß-Cell Death due to Pdx-1 Deficiency Requires Multi-BH Domain Protein Bax but Not Bak.
Academic Article Phase-locking regions in a forced model of slow insulin and glucose oscillations.
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