Abstract:
:This article is divided into two parts. A retrospective overview summarizes some of the work that provided the framework and tools of the more recent studies. The five novel areas of research are related to the indirect effects of insulin. Regulation of plasma glucose is of central importance in health and diabetes. Understanding this precise regulation requires sensitive isotope dilution methods that can measure the rates at which glucose is produced by the liver and used by the tissues on a minute-to-minute basis. Validation studies indicated that the non-steady-state tracer method yields reasonable results when the specific activity of plasma glucose does not change abruptly. During hyperinsulinemic glucose clamps, the decrease in specific activity of glucose can be prevented by the MSTI. During exercise, the decrease of specific activity can be only in part ameliorated by step-tracer infusion. Depancreatized dogs are used extensively as a model of selective insulin deficiency, because dog stomach secretes physiological amounts of glucagon. This strategy can avoid injections of somatostatin, which can have other affects in addition to the suppression of insulin and glucagon. In human diabetes, in addition to an increase of glucose production, there is also an increase in glucose cycling in the liver. In animal models of diabetes, mild NIDDM, and in glucose intolerance, the percentage of increments of glucose cycling are much larger than those of glucose production. We hypothesize, therefore, that measurements of glucose cycling can be used as an early marker of glucose intolerance. Application of different tracer strategies and use of the depancreatized dog as a model of diabetes, we investigated the importance of the indirect effects of insulin in the pathogenesis of diabetes. 1) Because, in the treatment of IDDM, insulin is administered by the peripheral routes we compared the relative importance of hepatic and peripheral effects of insulin in regulating the rate of glucose production. Experiments were performed in depancreatized dogs that were initially maintained at moderate hyperglycemia (10 mM) with subbasal portal insulin infusion. During the experimental period, insulin was infused either peripherally or portally at 0.9 mU.kg-1.min-1. In addition, peripheral infusions were also given at 0.45 mU.kg-1.min-1. We concluded that when suprabasal insulin levels are provided to moderately hyperglycemic depancreatized dogs, the suppression of glucose production is more dependent on peripheral than portal insulin concentrations. This indirect effect of insulin may be mediated by limitation of the flow of precursors and energy substrates for gluconeogenesis and/or by suppressive effect of insulin on glucagon secretion.(ABSTRACT TRUNCATED AT 400 WORDS)
journal_name
Diabetesjournal_title
Diabetesauthors
Vranic Mdoi
10.2337/diab.41.9.1188subject
Has Abstractpub_date
1992-09-01 00:00:00pages
1188-206issue
9eissn
0012-1797issn
1939-327Xjournal_volume
41pub_type
杂志文章,评审相关文献
DIABETES文献大全abstract::A single administration of complete Freund's adjuvant (CFA), type 1 carrageenan (Car), or silica 7, 2, and 2 days, respectively, before infection with a low dose (1 x 10(2) plaque-forming units/mouse) of encephalomyocarditis D (EMC-D) virus resulted in a significant increase in the incidence of diabetes in SJL/J mice ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.40.12.1586
更新日期:1991-12-01 00:00:00
abstract::We have attempted to define the nature of insulin secretory defect(s) in aged animals. In these studies, pancreatic islets were isolated from 2- and 18-mo-old Fischer 344 rats. Margination of secretion vesicles during exocytosis was assessed by measuring the recruitment of somatostatin (SRIF) receptors to the surface ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.34.11.1168
更新日期:1985-11-01 00:00:00
abstract::There has been a prejudice that diabetes modulates the function of saphenous vein in a manner that predisposes to bypass graft failure, although most of the evidence accrues from animal studies. We have investigated the effect of diabetes on the vasodilator responses and ultrastructure of saphenous vein harvested from...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.46.1.113
更新日期:1997-01-01 00:00:00
abstract:OBJECTIVE:Short sleep duration is associated with impaired glucose tolerance and an increased risk of diabetes. The effects of sleep restriction on insulin sensitivity have not been established. This study tests the hypothesis that decreasing nighttime sleep duration reduces insulin sensitivity and assesses the effects...
journal_title:Diabetes
pub_type: 杂志文章,随机对照试验
doi:10.2337/db09-0699
更新日期:2010-09-01 00:00:00
abstract:OBJECTIVE:We tested the hypothesis that adrenergic activation, cholinergic activation, or both, mediate the effect of recent antecedent hypoglycemia to reduce the sympathoadrenal response to subsequent hypoglycemia, the key feature of hypoglycemia-associated autonomic failure in diabetes, in humans. RESEARCH DESIGN AN...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db10-1374
更新日期:2011-02-01 00:00:00
abstract::Subjects with low serum HDL cholesterol levels are reported to be susceptible to diabetes, with insulin resistance believed to be the underlying pathological mechanism. Apolipoprotein M (apoM) is a carrier of sphingosine-1-phosphate (S1P), a multifunctional lipid mediator, on HDL, and the pleiotropic effects of HDL ar...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db19-0811
更新日期:2020-05-01 00:00:00
abstract::Neonatal morbidity was assessed in the offspring of 878 mothers with gestational diabetes mellitus (GDM), 132 mothers with pre-GDM, and 380 control subjects. Compared with the control group, the GDM group had a higher incidence of complications, including macrosomia, hypoglycemia, hyperbilirubinemia, hypocalcemia, pol...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.40.2.s74
更新日期:1991-12-01 00:00:00
abstract::Acute elevations of plasma free fatty acid (FFA) levels augment glucose-stimulated insulin secretion (GSIS). Prolonged elevations of FFA levels reportedly impair GSIS, but no one has previously compared GSIS after prolonged exposure to saturated or unsaturated fat. Rats received a low-fat diet (Low-Fat) or one enriche...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.6.1825
更新日期:2002-06-01 00:00:00
abstract::Muscle insulin sensitivity for stimulating glucose uptake is enhanced in the period after a single bout of exercise. We recently demonstrated that AMPK is necessary for AICAR, contraction, and exercise to enhance muscle and whole-body insulin sensitivity in mice. Correlative observations from both human and rodent ske...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db18-0769
更新日期:2019-09-01 00:00:00
abstract::Glucose controls islet beta-cell mass and function at least in part through the phosphatidylinositol 3-kinase (PI3K)/Akt pathway downstream of insulin signaling. The Foxo proteins, transcription factors known in other tissues to be negatively regulated by Akt activation, affect proliferation and metabolism. In this st...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db05-0678
更新日期:2006-06-01 00:00:00
abstract::Vascular endothelial growth factor receptor 2 (KDR) plays a critical role in mediating a variety of vasculogenic and angiogenic processes, including diabetic retinopathy. We previously demonstrated that the promoter activity of the KDR gene in retinal capillary endothelial cells (RCECs) was regulated in part by the re...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.5.1222
更新日期:2004-05-01 00:00:00
abstract::The aim of this study was to test the hypothesis that plasma leptin concentrations contributed to the pathophysiology of NIDDM by decreasing both insulin-mediated glucose disposal and glucose-stimulated insulin secretion. The study was performed in 60 women with normal oral glucose tolerance. Differences in insulin-me...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.47.2.244
更新日期:1998-02-01 00:00:00
abstract:OBJECTIVE:Aging increases the risk of developing impaired glucose tolerance (IGT) and type 2 diabetes. It has been proposed that increased reactive oxygen species (ROS) generation by dysfunctional mitochondria could play a role in the pathogenesis of these metabolic abnormalities. We examined whether aging per se (in s...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-0121
更新日期:2011-08-01 00:00:00
abstract::To determine the relationship between insulin sensitivity and beta-cell function, we quantified the insulin sensitivity index using the minimal model in 93 relatively young, apparently healthy human subjects of varying degrees of obesity (55 male, 38 female; 18-44 yr of age; body mass index 19.5-52.2 kg/m2) and with f...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.42.11.1663
更新日期:1993-11-01 00:00:00
abstract::A new murine model of porcine islet-like cell cluster (ICC) xenograft rejection, avoiding interference of unspecific inflammation, was introduced and used to investigate rejection mechanisms. Athymic (nu/nu) mice were transplanted with syngeneic, allogeneic, or xenogeneic islets under the kidney capsule. After the ori...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.5.1111
更新日期:2003-05-01 00:00:00
abstract::The long-term success of pancreatic islet transplantation (Tx) as a cure for type 1 diabetes remains limited. Islet loss after Tx related to apoptosis, inflammation, and other factors continues to limit Tx efficacy. In this project, we demonstrate a novel approach aimed at protecting islets before Tx in nonhuman prima...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db20-0517
更新日期:2020-11-01 00:00:00
abstract::African Americans are at increased risk of type 2 diabetes and many diabetes complications. We have carried out a genome-wide scan for African American type 2 diabetes using 638 affected sibling pairs (ASPs) from 247 families ascertained through impaired renal function to identify type 2 diabetes loci in this high-ris...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.3.830
更新日期:2004-03-01 00:00:00
abstract::Two previously described pedigrees with familial hyperproinsulinemia have elevated proinsulin conversion intermediates resulting from amino acid substitutions in the proinsulin molecule. In contrast, a third family with elevated levels of an apparently normal proinsulin molecule may have a defect in the converting pro...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.34.8.821
更新日期:1985-08-01 00:00:00
abstract::We conducted autosomal genome scans to map loci for metabolic syndrome (MES) and related traits in the Hong Kong Family Diabetes Study. We selected 55 families with 137 affected members (121 affected relative pairs) for nonparametric linkage analysis on MES. We also selected 179 families with 897 members (2,127 relati...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.10.2676
更新日期:2004-10-01 00:00:00
abstract::Diabetes is a common age-dependent complication of cystic fibrosis (CF) that is strongly influenced by modifier genes. We conducted a genome-wide association study in 3,059 individuals with CF (644 with CF-related diabetes [CFRD]) and identified single nucleotide polymorphisms (SNPs) within and 5' to the SLC26A9 gene ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db13-0510
更新日期:2013-10-01 00:00:00
abstract::Exercise bypasses insulin resistance to increase glucose uptake in skeletal muscle and therefore represents an important alternative to stimulate glucose uptake in insulin-resistant muscle. Both Rac1 and AMPK have been shown to partly regulate contraction-stimulated muscle glucose uptake, but whether those two signali...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-1138
更新日期:2017-06-01 00:00:00
abstract::A workshop sponsored by the National Institute of Child Health and Human Development was held in June 1988 to discuss the initial events in the pathogenesis of insulin-dependent diabetes and to make recommendations for future studies. Better definition of immunological markers to reliably predict the disease will enab...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diab.38.4.534
更新日期:1989-04-01 00:00:00
abstract::In skeletal muscle, the actin cytoskeleton-regulating GTPase, Rac1, is necessary for insulin-dependent GLUT4 translocation. Muscle contraction increases glucose transport and represents an alternative signaling pathway to insulin. Whether Rac1 is activated by muscle contraction and regulates contraction-induced glucos...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db12-0491
更新日期:2013-04-01 00:00:00
abstract::Elevated urinary albumin excretion (UAE) is a predictor of the development of nephropathy and cardiovascular mortality. To study whether genetic factors may determine UAE, we examined familial aggregation of UAE in 96 large multigenerational pedigrees ascertained for type 2 diabetes. A total of 1,269 subjects had UAE ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.49.6.1057
更新日期:2000-06-01 00:00:00
abstract:OBJECTIVE:Exercise is an important strategy for the treatment of type 2 diabetes. This is due in part to an increase in glucose transport that occurs in the working skeletal muscles. Glucose transport is regulated by GLUT4 translocation in muscle, but the molecular machinery mediating this process is poorly understood....
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db10-0233
更新日期:2010-09-01 00:00:00
abstract::Although recent studies show that adipose tissue macrophages (ATMs) participate in the inflammatory changes in obesity and contribute to insulin resistance, the properties of these cells are not well understood. We hypothesized that ATMs recruited to adipose tissue during a high-fat diet have unique inflammatory prope...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-1076
更新日期:2007-01-01 00:00:00
abstract::The aim of this study was to investigate the effects of elevated D-glucose concentrations on vascular smooth muscle cell (VSMC) expression of the platelet-derived growth factor (PDGF)beta receptor and VSMC migratory behavior. Immunoprecipitation, immunofluorescent staining, and RT-PCR of human VSMCs showed that elevat...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.2.519
更新日期:2003-02-01 00:00:00
abstract::We recently showed that a peptide of the M(r) 60,000 heat shock protein molecule, designated peptide p277, is a target of T-cells in autoimmune diabetes in NOD mice. Indeed, the p277 peptide could be used as a therapeutic agent to arrest the autoimmune process even after it was far advanced. The present study was done...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.44.9.1132
更新日期:1995-09-01 00:00:00
abstract::Capillary endothelial cells are thought to limit the transport of insulin across the endothelium, resulting in attenuated insulin action at target sites. Whether endothelial insulin transport is altered in dysglycemic insulin-resistant states is not clear and was therefore investigated in the JCR:LA-cp corpulent male ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.49.5.803
更新日期:2000-05-01 00:00:00
abstract::In adult humans, insulin resistance is associated with relatively low proportions of polyunsaturated fatty acids (PUFAs) in muscle membrane structural lipid. The aim of the present study was to determine the relationship between young children's muscle membrane fatty acid (FA) composition and indices of insulin resist...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.1.112
更新日期:1999-01-01 00:00:00