Abstract:
:Rhesus monkeys frequently develop obesity and insulin resistance followed by type 2 diabetes when allowed free access to chow. This insulin resistance is partly due to defective glucose transport into skeletal muscle. In this study, we examined signaling factors required for insulin-stimulated glucose transport in muscle biopsies taken during euglycemic-hyperinsulinemic clamps in nondiabetic, obese prediabetic, and diabetic monkeys. Insulin increased activities of insulin receptor substrate (IRS)-1-dependent phosphatidylinositol (PI) 3-kinase and its downstream effectors, atypical protein kinase Cs (aPKCs) (zeta/lambda/iota) and protein kinase B (PKB) in muscles of nondiabetic monkeys. Insulin-induced increases in glucose disposal and aPKC activity diminished progressively in prediabetic and diabetic monkeys. Decreases in aPKC activation appeared to be at least partly due to diminished activation of IRS-1-dependent PI 3-kinase, but direct activation of aPKCs by the PI 3-kinase lipid product PI-3,4,5-(PO(4))(3) was also diminished. In conjunction with aPKCs, PKB activation was diminished in prediabetic muscle but, differently from aPKCs, seemed to partially improve in diabetic muscle. Interestingly, calorie restriction and avoidance of obesity largely prevented development of defects in glucose disposal and aPKC activation. Our findings suggest that defective activation of aPKCs contributes importantly to obesity-dependent development of skeletal muscle insulin resistance in prediabetic and type 2 diabetic monkeys.
journal_name
Diabetesjournal_title
Diabetesauthors
Standaert ML,Ortmeyer HK,Sajan MP,Kanoh Y,Bandyopadhyay G,Hansen BC,Farese RVdoi
10.2337/diabetes.51.10.2936subject
Has Abstractpub_date
2002-10-01 00:00:00pages
2936-43issue
10eissn
0012-1797issn
1939-327Xjournal_volume
51pub_type
杂志文章相关文献
DIABETES文献大全abstract::We investigated the expression of Th1- and Th2-associated chemokine receptors on peripheral blood lymphocytes at diagnosis and in the first phase of type 1 diabetes. Peripheral blood mononuclear cells (PBMCs) of 25 patients with newly diagnosed type 1 diabetes, 10 patients with longstanding type 1 diabetes, and 35 hea...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.8.2474
更新日期:2002-08-01 00:00:00
abstract::Extensive investigations of the solubility and fluorescence of collagen fibers in diabetes have revealed that there are significant changes in their physical properties. These changes are associated with increased cross-link formation. We used X-ray diffraction to study these changes in human extensor tendons at a mol...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.40.3.391
更新日期:1991-03-01 00:00:00
abstract::Immunosuppressive drugs are routinely used to provide tolerance after whole pancreas and islet cell transplantations. While they are essential in inhibiting graft rejection, little is known about their effect on islet function and beta-cell viability. In this study, we report that tacrolimus, sirolimus, and mycophenol...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.2.424
更新日期:2005-02-01 00:00:00
abstract::Because skeletal muscle plays a major role in glucose disposal, it may be the primary site of insulin resistance in non-insulin-dependent diabetes mellitus (NIDDM). Rates of glycogen synthesis (GS), glucose utilization via glycolysis, glycolytic utilization (GU), and glucose transport (GT) were studied in epitrochlear...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.39.9.1106
更新日期:1990-09-01 00:00:00
abstract::Inactivation of the β-cell transcription factor NEUROD1 causes diabetes in mice and humans. In this study, we uncovered novel functions of NEUROD1 during murine islet cell development and during the differentiation of human embryonic stem cells (HESCs) into insulin-producing cells. In mice, we determined that Neurod1 ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db19-0117
更新日期:2019-12-01 00:00:00
abstract::Nonhuman primates have been used for a variety of studies on diabetes mellitus. Spontaneous, natural forms of diabetes have been well documented in several species; there are limited data on numerous other species that indicate diabetes or a diabetes-like syndrome. The causes and manifestations of spontaneous diabetes...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.31.1.s37
更新日期:1982-01-01 00:00:00
abstract::Patient-derived progenitor cell (PC) dysfunction is severely impaired in diabetes, but the molecular triggers that contribute to mechanisms of PC dysfunction are not fully understood. Methylglyoxal (MGO) is one of the highly reactive dicarbonyl species formed during hyperglycemia. We hypothesized that the MGO scavenge...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db18-0933
更新日期:2019-06-01 00:00:00
abstract::AMPK is a widely expressed intracellular energy sensor that monitors and modulates energy expenditure. Transient receptor potential ankyrin 1 (TRPA1) channel is a widely recognized chemical and thermal sensor that plays vital roles in pain transduction. In this study, we discovered a functional link between AMPK and T...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db17-0503
更新日期:2018-01-01 00:00:00
abstract:CONTEXT:Circulating fatty acid synthase (FASN) is a biomarker of metabolically demanding human diseases. The aim of this study was to determine whether circulating FASN could be a biomarker of overnutrition-induced metabolic stress and insulin resistance in common metabolic disorders. RESEARCH DESIGN AND METHODS:Circu...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-1756
更新日期:2010-06-01 00:00:00
abstract:OBJECTIVE:The gene encoding the alpha2 Heremans-Schmid glycoprotein (AHSG) is a credible biological and positional candidate gene for type 2 diabetes and the metabolic syndrome, and previous attempts to relate AHSG variation with type 2 diabetes and obesity in Swedish and French Caucasians have been largely successful....
journal_title:Diabetes
pub_type: 杂志文章,多中心研究
doi:10.2337/db07-0558
更新日期:2008-05-01 00:00:00
abstract::Thioredoxin-interacting protein (TXNIP) is an α-arrestin that can bind to and inhibit the antioxidant protein thioredoxin (TXN). TXNIP expression is induced by glucose and promotes β-cell apoptosis in the pancreas, and deletion of its gene in mouse models protects against diabetes. TXNIP is currently studied as a pote...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db18-0557
更新日期:2019-04-01 00:00:00
abstract::Filtered proteins including insulin are absorbed in the proximal tubule by means of pinocytosis. The first step in this process is binding of the protein to brush border membrane. As it is not known whether absorption exhibits specificity, we set out to determine whether specific binding sites for insulin are present ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.31.7.618
更新日期:1982-07-01 00:00:00
abstract::To elucidate the direct effect of rosiglitazone (RSG), a new thiazolidinedione antihyperglycemic agent, on pancreatic insulin secretion, an in situ investigation by rat pancreatic perfusion was performed. At a basal glucose concentration of 6 mmol/l, RSG (0.045-4.5 micromol/l) stimulated insulin release in a dose-depe...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.50.11.2598
更新日期:2001-11-01 00:00:00
abstract::Two major metabolic perturbations, increased polyol (sorbitol) pathway activity and reduced tissue myo-inositol content, are induced in peripheral nerve by hyperglycemia. Although they are commonly invoked as alternative biochemical pathogenetic mechanisms for diabetic neuropathy, their possible interrelationship has ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.32.11.988
更新日期:1983-11-01 00:00:00
abstract::The inhibitory actions of somatostatin (100 ng./ml.) on insulin release, stimulated by high glucose (20 mM), and on glucagon release, stimulated by arginine (15 mM), were studied with two in vitro systems: the isolated perifused rat islets prepared by the collagenase procedure and the isolated perfused rat pancreas. S...
journal_title:Diabetes
pub_type: 历史文章,杂志文章
doi:10.2337/diab.24.11.961
更新日期:1975-11-01 00:00:00
abstract::Effects of epinephrine (Epi) infusion on the absorption of subcutaneously injected 125I-labeled soluble human insulin (10 U) from the thigh or the abdomen were studied in 16 healthy subjects and from the thigh in 10 insulin-dependent diabetic (IDDM) patients. Epi was infused at 0.3 (high dose) or 0.1 (low dose; health...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.37.6.694
更新日期:1988-06-01 00:00:00
abstract::Bone morphogenetic proteins (BMPs) are a group of signaling molecules that belong to the TGF-β superfamily. Initially discovered for their ability to induce bone formation, BMPs are known to play a diverse and critical array of biological roles. We here focus on recent evidence showing that BMP4 is an important regula...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db20-0884
更新日期:2021-02-01 00:00:00
abstract::Using the hyperglycemic and euglycemic clamp, we demonstrated impaired β-cell function in obese youth with increasing dysglycemia. Herein we describe oral glucose tolerance test (OGTT)-modeled β-cell function and incretin effect in obese adolescents spanning the range of glucose tolerance. β-Cell function parameters w...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db13-1951
更新日期:2014-11-01 00:00:00
abstract::Adiponectin, an adipocyte protein important in insulin sensitization and cardioprotection, has a strong genetic component. We hypothesized that variants in the adiponectin gene (adipocyte collagen-domain containing [ACDC]) contribute to adiponectin levels in a biracial adolescent cohort. We genotyped 11 ACDC single nu...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.55.02.06.db05-0446
更新日期:2006-02-01 00:00:00
abstract::Rosiglitazone is an insulin-sensitizing agent that has recently been shown to exert beneficial effects on atherosclerosis. In addition to peroxisome proliferator-activated receptor (PPAR)-gamma, rosiglitazone can affect other targets, such as directly inhibiting recombinant long-chain acyl-CoA synthetase (ACSL)-4 acti...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-0267
更新日期:2007-04-01 00:00:00
abstract::Type 1 diabetes is a major histocompatibility complex (MHC) class II-associated autoimmune disease mediated by beta-cell-specific T-cells and characterized by circulating autoantibodies to beta-cell molecules. In the BB/Wor diabetes-prone (DP) rat, type 1 diabetes develops spontaneously with an incidence of >90%. BB d...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.5.975
更新日期:1999-05-01 00:00:00
abstract:OBJECTIVE:The catabasis of inflammation is an active process directed by n-3 derived pro-resolving lipid mediators. We aimed to determine whether high-fat (HF) diet-induced n-3 deficiency compromises the resolution capacity of obese mice and thereby contributes to obesity-linked inflammation and insulin resistance. RE...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db10-0054
更新日期:2010-12-01 00:00:00
abstract::GAD is a pancreatic beta-cell autoantigen in humans and nonobese diabetic (NOD) mice. Modulation of GAD expression in pancreatic beta-cells has been suggested to be associated with the development of autoimmune diabetes. Hormonal changes through environmental stimuli are considered to influence the expression of the d...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.9.2764
更新日期:2002-09-01 00:00:00
abstract::The beta-3 adrenergic receptor (ADRB3) has been implicated as a regulator of energy expenditure, and a polymorphism in codon 64 of this gene (Trp64Arg) has been associated in some studies with obesity and insulin resistance. However, many studies have failed to detect an effect of this variant, and the importance of t...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.9.1863
更新日期:1999-09-01 00:00:00
abstract::To clarify the relationship between variations in beta-cell mass and pancreatic function, we investigated the possibility to analyze, quantify, and sort beta-cell subpopulations with different functional maturity. To this aim, we tested the reliability of the sialylated form of neural cell adhesion molecule (NCAM) (PS...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.50.2007.s125
更新日期:2001-02-01 00:00:00
abstract::Leptin and glucagon-like peptide 1 (GLP-1) exhibit opposing actions in the endocrine pancreas. GLP-1 stimulates insulin biosynthesis, secretion, and islet growth, whereas leptin inhibits glucose-dependent insulin secretion and insulin gene transcription. In contrast, GLP-1 and leptin actions overlap in the central ner...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.49.9.1552
更新日期:2000-09-01 00:00:00
abstract::The experiments reported here investigate the effects of two conditions of elevated lactogen activity on the threshold of glucose stimulation of insulin secretion and suprathreshold, glucose-stimulated insulin secretion in the isolated, perfused rat pancreas. In both the tumor-bearing animals and pregnant animals, the...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.34.4.337
更新日期:1985-04-01 00:00:00
abstract:OBJECTIVE:Offspring of mothers with type 1 diabetes (OT1DM) demonstrate increased fat deposition, hyperinsulinemia, and hyperleptinemia in utero. We examined the influence of maternal diabetes on cord lipids at birth and relationship to body composition, cord insulin, leptin, and other hormonal measures. RESEARCH DESI...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db07-0585
更新日期:2007-11-01 00:00:00
abstract::Hormones produced by adipose tissue play a critical role in the regulation of energy intake, energy expenditure, and lipid and carbohydrate metabolism. This review will address the biology, actions, and regulation of three adipocyte hormones-leptin, acylation stimulating protein (ASP), and adiponectin-with an emphasis...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diabetes.53.2007.s143
更新日期:2004-02-01 00:00:00
abstract::We demonstrate the presence of specific insulinlike growth factor I (IGF-I) receptors in human adipocytes. Competition studies with 125I-labeled IGF-I and unlabeled IGF-I, IGF-II, and insulin showed the specificity of 125I-IGF-I binding to the IGF-I receptors in adipocytes, membranes, and partially purified detergent-...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.38.10.1217
更新日期:1989-10-01 00:00:00