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Polonsky, Kenneth S.

One or more keywords matched the following properties of 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	Blood Glucose
Concept	Glucose Tolerance Test
Concept	Glucose Clamp Technique
Concept	Glucose Intolerance
Concept	Glucose Transporter Type 2
Concept	Glucose Metabolism Disorders
Concept	Glucose
Concept	Glucose Transporter Type 4
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	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	Analytical problems in detecting rapid insulin secretory pulses in normal humans.
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	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	Treatment with the oral antidiabetic agent troglitazone improves beta cell responses to glucose in subjects with impaired glucose tolerance.
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	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	Roles of circadian rhythmicity and sleep in human glucose regulation.
Academic Article	A practical approach to fasting hypoglycemia.
Academic Article	Defective insulin secretion in hepatocyte nuclear factor 1alpha-deficient mice.
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	Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young.
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	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	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	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	RyR2 and calpain-10 delineate a novel apoptosis pathway in pancreatic islets.
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	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	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	Calpain system regulates muscle mass and glucose transporter GLUT4 turnover.
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	Postprandial lipoprotein metabolism in normal and obese subjects: comparison after the vitamin A fat-loading test.
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	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	Proinsulin radioimmunoassay in the evaluation of insulinomas and familial hyperproinsulinemia.
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	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	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	Quantitative evaluation of the effect of low-intensity exercise on insulin secretion in man.
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	Abnormal patterns of insulin secretion in non-insulin-dependent diabetes mellitus.
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	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	A familial glucagonoma syndrome: genetic, clinical and biochemical features.
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	Pancreatic hormone profiles and metabolism posthepatectomy in the dog. Evidence for a hepatotrophic role of insulin, glucagon, and pancreatic polypeptide.
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	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	Prior feeding alters the response to the 50-g glucose challenge test in pregnancy. The Staub-Traugott effect revisited.
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	Insulin secretion in insulin-resistant women with a history of gestational diabetes.
Academic Article	Xenin-25 potentiates glucose-dependent insulinotropic polypeptide action via a novel cholinergic relay mechanism.
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	Relation of counterregulatory responses to hypoglycemia in type I diabetics.
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	Abnormal insulin secretion, not insulin resistance, is the genetic or primary defect of MODY in the RW pedigree.
Academic Article	Inhibition of calpain results in impaired contraction-stimulated GLUT4 translocation in skeletal muscle.
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	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	Complex patterns of metabolic and Ca²? entrainment in pancreatic islets by oscillatory glucose.
Academic Article	Xenin-25 delays gastric emptying and reduces postprandial glucose levels in humans with and without type 2 diabetes.
Academic Article	Phase-locking regions in a forced model of slow insulin and glucose oscillations.

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