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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
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	Ultradian oscillations of leptin secretion in humans.
Academic Article	Alterations in the kinetics of C-peptide and insulin secretion in hyperthyroidism.
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	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	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	Maturity onset diabetes of the young (MODY).
Academic Article	Diurnal variations in cardiovascular function and glucose regulation in normotensive humans.
Academic Article	Alternative insulin delivery systems: how demanding should the patient be?
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	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	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	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	Diabetes mellitus and genetically programmed defects in beta-cell function.
Academic Article	Modulation of glucose regulation and insulin secretion by circadian rhythmicity and sleep.
Academic Article	Increased islet apoptosis in Pdx1+/- mice.
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	Entrainment of pulsatile insulin secretion by oscillatory glucose infusion.
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	Rosiglitazone reduces glucose-stimulated insulin secretion rate and increases insulin clearance in nondiabetic, insulin-resistant individuals.
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	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	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	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	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	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	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	Effect of glyburide on beta cell responsiveness to glucose in non-insulin-dependent diabetes mellitus.
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	Insulin secretion and clearance. Comparison after oral and intravenous glucose.
Academic Article	Evolution of beta-cell dysfunction in the male Zucker diabetic fatty rat.
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	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	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	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	Human insulin B24 (Phe----Ser). Secretion and metabolic clearance of the abnormal insulin in man and in a dog model.
Academic Article	Lilly Lecture 1994. The beta-cell in diabetes: from molecular genetics to clinical research.
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	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	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	Impaired insulin secretion in transgenic mice over-expressing calpastatin in pancreatic ß-cells.
Academic Article	Effects of aging on insulin secretion.
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	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.

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