Abstract:
:We report the results of cross-sectional, prospective, and longitudinal studies identifying etiologic metabolic factors in the susceptibility to type 2 diabetes mellitus of the Pima Indians of Arizona, whose prevalence and incidence rates of the disease are the highest in the world. Diabetic Pima Indians are metabolically prototypic, with obesity, insulin resistance, a reduced acute insulin response to glucose, and increased endogenous glucose production. Cross-sectional studies show that the acute insulin response is absent in diabetic subjects and lower in impaired than in normal glucose-tolerant subjects. Prospective studies using proportional hazards analyses indicate that insulin resistance and a relatively low acute insulin response predict diabetes independently of age, gender, and each other, with obesity increasing susceptibility by worsening one or both predictors. Longitudinal studies show that glucose tolerance deteriorates as the degree of obesity increases due to worsening insulin resistance and decreases in early insulin secretion. Furthermore, since the children of diabetic pregnancies are at much greater risk of developing diabetes at a young age than those of nondiabetic pregnancies, the diabetic uterine environment may induce insulin resistance and/or reduced insulin secretion: early evidence confirms that adult normal glucose-tolerant offspring show a substantially decreased acute insulin response--the clearest demonstration yet of an environmental condition increasing susceptibility to type 2 diabetes mellitus. However, the genetic determinants require elucidation: correlation of the acute insulin response with the age of parental diabetes onset in fathers as well as mothers indicates a mechanism independent of the diabetic uterine environment.
journal_name
Diabetesjournal_title
Diabetesauthors
Bogardus C,Tataranni PAdoi
10.2337/diabetes.51.2007.s262subject
Has Abstractpub_date
2002-02-01 00:00:00pages
S262-4eissn
0012-1797issn
1939-327Xjournal_volume
51 Suppl 1pub_type
杂志文章,评审相关文献
DIABETES文献大全abstract::The adipocyte-secreted protein adiponectin is associated with insulin sensitivity in observational studies. We aimed to evaluate whether this relationship is causal using a Mendelian randomization approach. In a sample of Swedish men aged 71 years (n = 942) from the Uppsala Longitudinal Study of Adult Men (ULSAM), ins...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db12-0935
更新日期:2013-04-01 00:00:00
abstract::With an estimated prevalence of 463 million affected, type 2 diabetes represents a major challenge to health care systems worldwide. Analyzing the plasma proteomes of individuals with type 2 diabetes may illuminate hitherto unknown functional mechanisms underlying disease pathology. We assessed the associations betwee...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db20-0296
更新日期:2020-12-01 00:00:00
abstract::Human fetal pancreatic glands were obtained from 12 consecutive prostaglandin-induced abortions. Explants cultured for 1 day were frozen at 0.3 degree C/min in a 1 M DMSO-containing medium and stored at -196 degrees C. After storage for 3-4 mo the frozen material was rapidly thawed and cultured 1 day before being test...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.31.3.238
更新日期:1982-03-01 00:00:00
abstract::Carbohydrate-responsive element-binding protein (ChREBP) is a glucose-sensing transcription factor required for glucose-stimulated proliferation of pancreatic β-cells in rodents and humans. The full-length isoform (ChREBPα) has a low glucose inhibitory domain (LID) that restrains the transactivation domain when glucos...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db15-0239
更新日期:2015-12-01 00:00:00
abstract::The decline of leptin (Ob protein) concentrations during fasting is implicated as a signal for increasing the expression of the orexigenic peptide neuropeptide Y (NPY) in the hypothalamus. To test the hypothesis that the effects of food intake on arcuate nucleus NPY activation are mediated by leptin, we performed simu...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.4.828
更新日期:1999-04-01 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::It is well described that excessive lipid metabolism can cause insulin resistance in both animals and humans, and this has been implicated as a causative factor in the development of insulin resistance and type 2 diabetes in humans. Recently, we have shown that intravenous lipid emulsion (liposyn) infusion during a 12...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.6.1907
更新日期:2002-06-01 00:00:00
abstract::Sera from rats inoculated with in vitro glucosylated rat skin acid-soluble collagen were evaluated for specific antibody response using the enzyme-linked immunosorbent assay. The data indicate that the altered protein is capable of eliciting the production of antibodies, but unmodified collagen is not. The specificity...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.32.12.1182
更新日期:1983-12-01 00:00:00
abstract::Vascular endothelial growth factor (VEGF) has been suggested to play a role in the pathogenesis of diabetic vascular complications. In the present study, we investigated whether expression of monocyte chemoattractant protein-1 (MCP-1), a chemokine that has been proposed to recruit leukocytes to sites of inflammation, ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.5.1131
更新日期:1999-05-01 00:00:00
abstract::Triglycerides in the beta-cell may be important for stimulus-secretion coupling, through provision of a lipid-derived signal, and for pathogenetic events in NIDDM, where lipids may adversely affect beta-cell function. In adipose tissues, hormone-sensitive lipase (HSL) is rate-limiting in triglyceride hydrolysis. Here,...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.1.228
更新日期:1999-01-01 00:00:00
abstract::Cultured bovine retinal capillary pericytes (BRP) were used to investigate the effect of an aldose reductase inhibitor, tolrestat, and an inhibitor of advanced glycation end products (AGE) formation, aminoguanidine, on glucose toxicity. Glucose at high concentration reduced the replicative activity of pericytes in a d...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.43.6.758
更新日期:1994-06-01 00:00:00
abstract::In humans, low levels of growth hormone (GH) and its mediator, IGF-1, associate with hepatic lipid accumulation. In mice, congenital liver-specific ablation of the GH receptor (GHR) results in reductions in circulating IGF-1 and hepatic steatosis, associated with systemic insulin resistance. Due to the intricate relat...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-0649
更新日期:2016-12-01 00:00:00
abstract::MDL 29311, an analogue of probucol, administered to rats as a 1% dietary admixture for 2 wk before and 5 days after intravenous injection of 40 mg/kg of ALX significantly (P < 0.05) reduced plasma glucose (6.9 +/- 0.3 vs. 19.2 +/- 1.3 mM) and serum triglyceride (0.17 +/- 0.01 vs. 1.82 +/- 0.39 mM) levels in overnight-...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.42.8.1179
更新日期:1993-08-01 00:00:00
abstract::The hyperinsulinemia of obese rodents has been associated with a reduced number of hepatic insulin receptors except in hepatocytes from fatty Zucker rats. We isolated liver plasma membranes from 10-11-wk-old lean and fatty Zucker rats, some of which were injected with streptozotocin 2--4 wk earlier. We have determined...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.31.10.867
更新日期:1982-10-01 00:00:00
abstract::As part of an ongoing search for susceptibility loci for NIDDM, we tested 19 genes whose products are implicated in insulin secretion or action for linkage with NIDDM. Loci included the G-protein-coupled inwardly rectifying potassium channels expressed in beta-cells (KCNJ3 and KCNJ7), glucagon (GCG), glucokinase regul...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.46.6.1062
更新日期:1997-06-01 00:00:00
abstract:OBJECTIVE:In part, activation of invariant natural killer T (iNKT)-cells with the superagonist alpha-galactosylceramide (alpha-GalCer) inhibits the development of T-cell-mediated autoimmune type 1 diabetes in NOD mice by inducing the downstream differentiation of antigen-presenting dendritic cells (DCs) to an immunotol...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-1116
更新日期:2010-02-01 00:00:00
abstract::Phorbol esters translocatively activate and subsequently downregulate protein kinase C and insulin-stimulated glucose uptake in rat adipocytes. This study examined the possibility that other translocative activators of protein kinase C in rat adipocytes, e.g., insulin and glucose, provoke similar downregulating effect...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.40.10.1274
更新日期:1991-10-01 00:00:00
abstract::Human fetal pancreas has been obtained after the therapeutic termination of pregnancy with prostaglandin F2 alpha. Pancreatic explants were studied in a perifusion system and maintained in organ culture for up to 3 wk. Insulin biosynthesis was stimulated by glucose; however, the incorporation of 3H-L-leucine into proi...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.29.1.s57
更新日期:1980-01-01 00:00:00
abstract:OBJECTIVE:The presence of autoantibodies to islet antigens GAD and/or tyrosine phosphatase 2 (IA-2) in type 2 diabetic patients (latent autoimmune diabetes in adults [LADA]) identifies subjects at high risk to develop insulin dependency. The aim of this study was to dissect humoral anti-IA-2 immune response in Caucasia...
journal_title:Diabetes
pub_type: 杂志文章,多中心研究
doi:10.2337/db07-0874
更新日期:2008-05-01 00:00:00
abstract::In humans, the glucagon response to moderate-to-marked insulin-induced hypoglycemia (IIH) is largely mediated by the autonomic nervous system. Because this glucagon response is impaired early in type 1 diabetes, we sought to determine if these patients, like animal models of autoimmune diabetes, have an early and seve...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-0284
更新日期:2016-08-01 00:00:00
abstract::Dysfunctional T cells can mediate autoimmunity, but the inaccessibility of autoimmune tissues and the rarity of autoimmune T cells in the blood hinder their study. We describe a method to enrich and harvest autoimmune T cells in vivo by using a biomaterial scaffold loaded with protein antigens. In model antigen system...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-0946
更新日期:2017-08-01 00:00:00
abstract::Toll-like receptor 9 (TLR9) is highly expressed in B cells, and B cells are important in the pathogenesis of type 1 diabetes (T1D) development. However, the intrinsic effect of TLR9 in B cells on β-cell autoimmunity is not known. To fill this knowledge gap, we generated NOD mice with a B-cell-specific deficiency of TL...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db20-0373
更新日期:2021-02-01 00:00:00
abstract::Large genome-wide association studies of glycemic traits have identified genetics variants that are associated with insulin resistance (IR) in the general population. It is unknown whether people with genetic enrichment for these IR variants respond differently to interventions that aim to improve insulin sensitivity....
journal_title:Diabetes
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.2337/db15-0950
更新日期:2016-02-01 00:00:00
abstract::The anionic charge on the surface of the erythrocyte and the erythrocyte membrane content of sialic acid and acid glycosaminoglycans (GAGs) were evaluated in insulin-dependent diabetic patients who had albumin excretion rates less than 300 mg/24 h. In these subjects a statistically significant reduction of erythrocyte...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.37.6.745
更新日期:1988-06-01 00:00:00
abstract::Six men with a low rate of insulin-stimulated, non-oxidative carbohydrate disposal (storage) and six with a high storage rate were recruited for study of the fate of insulin-stimulated glucose uptake. [3-3H]glucose was infused before and during a 4-h hyperinsulinemic euglycemic clamp procedure in a dosage regimen desi...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.37.3.303
更新日期:1988-03-01 00:00:00
abstract::Obesity is associated with an increased risk for the development of type 2 diabetes and vascular complications. Advanced glycation end products are increased in adipose tissue and have been associated with insulin resistance, vascular dysfunction, and inflammation of adipose tissue. Here, we report that delayed interv...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db15-1390
更新日期:2016-04-01 00:00:00
abstract::Glucagon-like peptide 1 (GLP-1) is a potent glucose-lowering agent of potential interest for the treatment of type 2 diabetes. To evaluate actions of NN2211, a long-acting GLP-1 derivative, we examined 11 patients with type 2 diabetes, age 59 +/- 7 years (mean +/- SD), BMI 28.9 +/- 3.0 kg/m(2), HbA(1c) 6.5 +/- 0.6%, i...
journal_title:Diabetes
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2337/diabetes.51.2.424
更新日期:2002-02-01 00:00:00
abstract::There is evidence from animal models of obesity and type 2 diabetes that increased parasympathetic vagal input to the pancreas contributes to hyperinsulinemia. Compared with Caucasians, Pima Indians have a high risk of type 2 diabetes and exhibit marked hyperinsulinemia and elevated plasma levels of pancreatic polypep...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.3.663
更新日期:2004-03-01 00:00:00
abstract::Cytoplasmic islet cell antibody-negative (ICA-; less than 20 Juvenile Diabetes Foundation units, n = 1670) and ICA+ (n = 42) first-degree relatives of type I (insulin-dependent) diabetic individuals were studied for competitive insulin autoantibodies (CIAAs) with a radioassay. Overall, 3.7% of first-degree relatives (...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.38.10.1320
更新日期:1989-10-01 00:00:00
abstract::Ectopic lipids in peripheral tissues have been implicated in attenuating insulin action in vivo. The botanical extract of Artemisia dracunculus L. (PMI 5011) improves insulin action, yet the precise mechanism is not known. We sought to determine whether the mechanism by which PMI 5011 improves insulin signaling is thr...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-0396
更新日期:2012-03-01 00:00:00