Abstract:
:In the fasted rat, efficient glucose-stimulated insulin secretion (GSIS) is absolutely dependent on an elevated level of circulating free fatty acids (FFAs). To determine if this is also true in humans, nonobese volunteers were fasted for 24 h (n = 5) or 48 h (n = 5), after which they received an infusion of either saline or nicotinic acid (NA) to deplete their plasma FFA pool, followed by an intravenous bolus of glucose. NA treatment resulted in a fall in basal insulin concentrations of 35 and 45% and in the area under the insulin response curve (area under the curve [AUC]) to glucose of 47 and 42% in the 24- and 48-h fasted individuals, respectively. The 48-h fasted subjects underwent the same procedure with the addition of a coinfusion of Intralipid plus heparin (together with NA) to maintain a high concentration of plasma FFAs throughout the study. The basal level and AUC for insulin were now completely normalized (C-peptide profiles paralleled those for insulin). To assess the effect of an overnight fast, nonobese (n = 6) and obese (n = 6) subjects received an infusion of either saline or NA, followed by a hyperglycemic clamp (200 mg/dl). The insulin AUC in response to glucose was unaffected by lowering of the FFA level in nonobese subjects, but fell by 29% in the obese group. The data clearly demonstrate that in humans, the rise in circulating FFA levels after 24 and 48 h of food deprivation is critically important for pancreatic beta-cell function both basally and during subsequent glucose loading. They also suggest that the enhancement of GSIS by FFAs in obese individuals is more prominent than that seen in their nonobese counterparts.
journal_name
Diabetesjournal_title
Diabetesauthors
Dobbins RL,Chester MW,Daniels MB,McGarry JD,Stein DTdoi
10.2337/diabetes.47.10.1613subject
Has Abstractpub_date
1998-10-01 00:00:00pages
1613-8issue
10eissn
0012-1797issn
1939-327Xjournal_volume
47pub_type
杂志文章相关文献
DIABETES文献大全abstract::Nerve regeneration in diabetic animals is delayed and qualitatively impaired, but the mechanisms responsible for these defects have not been elucidated. The extracellular matrix protein laminin promotes the extension of neuronal processes, and recent studies have localized neurite-promoting activity to a lysine-contai...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.42.4.509
更新日期:1993-04-01 00:00:00
abstract::Pancreatic beta-cell survival is critical in the setting of diabetes as well as in islet transplantation. Transgenic mice overexpressing parathyroid hormone-related protein (PTHrP) targeted to beta-cells using the rat insulin II promoter (RIP) display hyperinsulinemia, hypoglycemia, and islet hyperplasia, without a co...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.10.3003
更新日期:2002-10-01 00:00:00
abstract::Flow-mediated remodeling of resistance arteries is essential for revascularization in ischemic diseases, but this is impaired in diabetes. We hypothesized that breaking advanced glycation end product (AGE) cross-links could improve remodeling in mesenteric resistance arteries in Zucker diabetic fatty (ZDF) rats compar...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-0750
更新日期:2012-06-01 00:00:00
abstract::Prostaglandin E (PGE) infusion in normal man inhibits the acute insulin response to glucose. In order to determine whether endogenously released PGE might also inhibit insulin secretion, glucose-stimulated insulin responses were investigated in normal volunteers after furosemide (40 mg i.v.), a stimulator of endogenou...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.28.9.841
更新日期:1979-09-01 00:00:00
abstract:OBJECTIVE:Glucagon-like peptide-1 (GLP-1) is a growth and differentiation factor for mature beta-cells and their precursors. However, the overall effect of GLP-1 on increasing beta-cell mass in both in vivo and in vitro conditions is relatively small, and augmenting this effect would be beneficial for the treatment or ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db07-1414
更新日期:2008-03-01 00:00:00
abstract:OBJECTIVE:Recent genome-wide association studies (GWASs) related common variants in the interleukin-6 (Il-6) receptor (IL6R) gene to plasma C-reactive protein (CRP) concentrations. Because IL6R variants were previously associated with IL-6 levels, we tested whether the associations with CRP were independent of IL-6 and...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db08-0968
更新日期:2009-01-01 00:00:00
abstract::One of the unique features of beta-cells is their relatively low expression of many antioxidant enzymes. This could render beta-cells susceptible to oxidative damage but may also provide a system that is sensitive to reactive oxygen species as signals. In isolated mouse islets and INS-1(832/13) cells, glucose increase...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-1601
更新日期:2007-07-01 00:00:00
abstract::In man a small dose of somatostatin (50 micrograms/h) suppressed moderately basal insulin (5 microU/ml) and glucagon (40 pg/ml) levels. This resulted in a short-lasting hypoglycemia, which was then followed by marginal hyperglycemia throughout the experiment. The addition of a minimal dose of glucagon (0.50 ng/kg/min)...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.32.7.633
更新日期:1983-07-01 00:00:00
abstract:OBJECTIVE:Insulin resistance in skeletal muscle is a major risk factor for type 2 diabetes in women with polycystic ovary syndrome (PCOS). However, the molecular mechanisms underlying skeletal muscle insulin resistance and the insulin-sensitizing effect of thiazolidinediones in PCOS in vivo are less well characterized....
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db07-0706
更新日期:2008-02-01 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::Because polyphenols may have beneficial effects on dyslipidemia, which accelerates atherosclerosis in diabetes, we examined the effect of polyphenols on hepatocellular AMP-activated protein kinase (AMPK) activity and lipid levels, as well as hyperlipidemia and atherogenesis in type 1 diabetic LDL receptor-deficient mi...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db05-1188
更新日期:2006-08-01 00:00:00
abstract::AS160 is a newly described substrate for the protein kinase Akt that links insulin signaling and GLUT4 trafficking. In this study, we determined the expression of and in vivo insulin action on AS160 in human skeletal muscle. In addition, we compared the effect of physiological hyperinsulinemia on AS160 phosphorylation...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.6.1692
更新日期:2005-06-01 00:00:00
abstract::This article seeks to determine whether factors related to autoimmunity risk remain significant after the initiation of two or more diabetes-related autoantibodies and continue to contribute to type 1 diabetes (T1D) risk among autoantibody-positive children in The Environmental Determinants of Diabetes in the Young (T...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db17-0261
更新日期:2017-12-01 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::Several recent reports claim the generation of insulin-producing cells from embryonic stem cells via the differentiation of progenitors that express nestin. Here, we investigate further the properties of these insulin-containing cells. We find that although differentiated cells contain immunoreactive insulin, they do ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.10.2603
更新日期:2004-10-01 00:00:00
abstract::It is well known that peripherally administered growth hormone (GH) results in decreased body fat mass. However, GH-deficient patients increase their food intake when substituted with GH, suggesting that GH also has an appetite stimulating effect. Transgenic mice with an overexpression of bovine GH in the central nerv...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.1.51
更新日期:2005-01-01 00:00:00
abstract::WISP1 (Wnt1-inducible signaling pathway protein-1, also known as CCN4) is a member of the secreted extracellular matrix-associated proteins of the CCN family and a target gene of the Wingless-type (WNT) signaling pathway. Growing evidence links the WNT signaling pathway to the regulation of adipogenesis and low-grade ...
journal_title:Diabetes
pub_type: 临床试验,杂志文章
doi:10.2337/db14-0444
更新日期:2015-03-01 00:00:00
abstract::In IDDM, the gluconeogenic turnover of amino acids is increased even if glycemia is well controlled and may be restored to normal by means of prehepatic insulin substitution. Therefore, the present study was designed 1) to investigate the influence of route of insulin administration (portal versus peripheral) on the u...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.45.5.667
更新日期:1996-05-01 00:00:00
abstract::Active maintenance of β-cell identity through fine-tuned regulation of key transcription factors ensures β-cell function. Tacrolimus, a widely used immunosuppressant, accelerates onset of diabetes after organ transplantation, but underlying molecular mechanisms are unclear. Here we show that tacrolimus induces loss of...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db19-0828
更新日期:2020-02-01 00:00:00
abstract::It is well established that patients with non-insulin-dependent diabetes mellitus (NIDDM) are resistant to insulin. However, the contribution of hepatic and extrahepatic tissues to insulin resistance remains controversial. The uncertainty may be at least in part due to errors introduced by the unknowing use in previou...
journal_title:Diabetes
pub_type: 临床试验,杂志文章
doi:10.2337/diab.39.2.217
更新日期:1990-02-01 00:00:00
abstract::The relationship between plasma C-peptide and the frequency and severity of diabetic retinopathy was examined in a population-based study in Wisconsin in 1984-1986. Individuals with younger- (n = 835) and older- (n = 940) onset diabetes were included. C-peptide was measured by radioimmunoassay with Heding's M1230 anti...
journal_title:Diabetes
pub_type: 临床试验,杂志文章
doi:10.2337/diab.39.11.1445
更新日期:1990-11-01 00:00:00
abstract::Evidence from animal models suggests that natural killer (NK) cells can be important players in the development of type 1 diabetes, although data in humans are still sparse. We studied the frequency and activation state of blood NK cells at different stages of human type 1 diabetes, and whether genetic or phenotypic N...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-0493
更新日期:2007-01-01 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::Glucose sensing is essential for the ability of pancreatic beta-cells to produce insulin in sufficient quantities to maintain blood glucose within the normal range. Stress causes the release of adrenergic hormones that increase circulating glucose by promoting glucose production and inhibiting insulin release. We have...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.55.04.06.db05-1266
更新日期:2006-04-01 00:00:00
abstract::In the transgenic mouse, a specific gene can be transduced or deleted to study its function and relation to human diseases. Recently, various lines of transgenic mice that overexpress or lack a specific gene have been established and are available to study the pathophysiology of human diseases, including atheroscleros...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.45.3.s129
更新日期:1996-07-01 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::This cross-sectional study evaluated the relationship between 1) functional and structural measurements of neurodegeneration in the initial stages of diabetic retinopathy (DR) and 2) the presence of neurodegeneration and early microvascular impairment. We analyzed baseline data of 449 patients with type 2 diabetes enr...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-1453
更新日期:2017-09-01 00:00:00
abstract::Diabetes complications are caused by hyperglycemia. Hyperglycemia results in increased concentrations of glucose degradation products. The study of peritoneal dialysis solution biocompatibility has highlighted the adverse effects of glucose degradation products. Recently, 3,4-dideoxyglucosone-3-ene (3,4-DGE) has been ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.8.2424
更新日期:2005-08-01 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 enzyme activities of mitochondrial glycerol phosphate dehydrogenase (mGPD) (EC 1.1.99.5) and pyruvate carboxylase (PC) (EC 6.4.1.1) have been reported to be low in the pancreatic islet of several rodent models of NIDDM. The present study was undertaken to discern whether mGPD is abnormal in the Zucker diabetic fat...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.45.11.1626
更新日期:1996-11-01 00:00:00