Abstract:
:The secretory, metabolic, and signaling aspects of glucose/palmitate interaction on beta-cell function have been studied on rat islets. Palmitate potentiated the glucose-induced insulin response of perifused islets at suprathreshold (>3 mmol/l) sugar concentrations. This potentiating effect could be suppressed by 8-bromo-cGMP, which also blocks palmitate metabolism. Palmitate did not modify glucose utilization, but it slightly reduced glucose oxidation and concomitantly increased lactate production. The very low rate of palmitate oxidation (80-fold lower than that of 20 mmol/l glucose) might explain its lack of effect on glycolysis and hence that the glucose/fatty acid cycle is inoperative in islet cells. However, glucose determines the metabolic fate of exogenous palmitate, which is mainly diverted toward lipid synthesis at high sugar concentrations and might then generate lipid messengers for cell signaling. Palmitate did not increase glucose-induced production of inositol-1,4,5-trisphosphate, but it stimulated the translocation of protein kinase C activity from a cytosolic to a particulate fraction at 20 but not at 3 mmol/l glucose. This increased translocation was partially or completely blocked by hydroxycitrate or 8-bromo-cGMP, respectively, which are agents interfering with palmitate metabolism (inhibiting lipid synthesis). The metabolic interaction between glucose and palmitate might generate lipid messengers (diacylglycerol, phosphatidylserine) necessary for the activation of islet protein kinase C, which would in turn result in a potentiation of glucose-induced insulin secretion.
journal_name
Diabetesjournal_title
Diabetesauthors
Alcázar O,Qiu-yue Z,Giné E,Tamarit-Rodriguez Jdoi
10.2337/diab.46.7.1153subject
Has Abstractpub_date
1997-07-01 00:00:00pages
1153-8issue
7eissn
0012-1797issn
1939-327Xjournal_volume
46pub_type
杂志文章相关文献
DIABETES文献大全abstract:OBJECTIVE:This study aimed to estimate the current cumulative risk of end-stage renal disease (ESRD) due to diabetic nephropathy in a large, nationwide, population-based prospective type 1 diabetes cohort and specifically study the effects of sex and age at onset. RESEARCH DESIGN AND METHODS:In Sweden, all incident ca...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-1744
更新日期:2010-07-01 00:00:00
abstract::Kir6.2 is an inwardly rectifying potassium channel that is expressed in pancreatic beta-cells and cardiac and skeletal muscle. Expressed together with the high-affinity sulphonylurea receptor, it reconstitutes a sulphonylurea- and also ATP-sensitive potassium channel resembling the native beta-cell channel. The object...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.46.3.508
更新日期:1997-03-01 00:00:00
abstract::The antidiabetic thiazolidinediones, which include troglitazone and rosiglitazone, are ligands for the nuclear receptor peroxisome proliferator-activated receptor (PPAR)-gamma and exert their antihyperglycemic effects by regulation of PPAR-gamma-responsive genes. We report here that PPAR-gamma activation by troglitazo...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.49.4.539
更新日期:2000-04-01 00:00:00
abstract::Signaling pathways activated by leptin in metabolically important organs have largely been studied only in animal and/or cell culture studies. In this study, we examined whether leptin has similar effects in human peripheral tissues in vivo, ex vivo, and in vitro and whether the response would be different in lean and...
journal_title:Diabetes
pub_type: 临床试验,杂志文章
doi:10.2337/db14-0625
更新日期:2015-03-01 00:00:00
abstract::Genome-wide nonparametric linkage analysis of 480 sib-pairs affected with type 2 diabetes revealed linkage to a previously unreported susceptibility locus on chromosome 18p11. This result improved with stringent subphenotyping using age- and sex-adjusted BMI, ultimately reaching a logarithm of odds of 3.82 (allele sha...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.50.3.675
更新日期:2001-03-01 00:00:00
abstract::We previously showed that pancreatic beta-cells express a neuronal isoform of nitric oxide synthase (nNOS) that controls insulin secretion by exerting two enzymatic activities: nitric oxide (NO) production and cytochrome c reductase activity. We now bring evidence that two inhibitors of nNOS, N-omega-nitro-l-arginine ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.6.1467
更新日期:2004-06-01 00:00:00
abstract::Growing evidence suggests that epigenetic profile changes occurring during fetal development in response to in utero environment variations could be one of the mechanisms involved in the early determinants of adult chronic diseases. In this study, we tested whether maternal glycemic status is associated with the adipo...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-1160
更新日期:2012-05-01 00:00:00
abstract::Skeletal muscle insulin resistance plays a key role in the pathogenesis of type 2 diabetes. It recently has been hypothesized that excessive activity of the inhibitor of kappaB (IkappaB)/nuclear factor kappaB (NFkappaB) inflammatory pathway is a mechanism underlying skeletal muscle insulin resistance. However, it is n...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.55.03.06.db05-0677
更新日期:2006-03-01 00:00:00
abstract:OBJECTIVE:We have previously reported a highly diabetogenic CD8 T-cell clone, G9C8, in the nonobese diabetic (NOD) mouse, specific to low-avidity insulin peptide B15-23, and cells responsive to this antigen are among the earliest islet infiltrates. We aimed to study the selection, activation, and development of the dia...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db08-0800
更新日期:2009-05-01 00:00:00
abstract::A simple method for the elimination of labile glycohemoglobin in the chromatographic quantitation of glycosylated hemoglobin is described. Use is made of the instability of Schiff base adducts in acidic solution. Erythrocytes are lysed with a pH 5 buffer. At this pH dissociation reaches completion during sample prepar...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.31.7.630
更新日期:1982-07-01 00:00:00
abstract::Type 1 diabetes (T1D) remains a major health problem worldwide, with a steadily rising incidence yet no cure. Phosphoinositide 3-kinase-γ (PI3Kγ), a member of a family of lipid kinases expressed primarily in leukocytes, has been the subject of substantial research for its role in inflammatory diseases. However, the ro...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-0134
更新日期:2012-06-01 00:00:00
abstract::Using an integrative approach in which genetic variation, gene expression, and clinical phenotypes are assessed in relevant tissues may help functionally characterize the contribution of genetics to disease susceptibility. We sought to identify genetic variation influencing skeletal muscle gene expression (expression ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db13-1301
更新日期:2014-03-01 00:00:00
abstract::Changes in tissue levels of sorbitol, myo-inositol, and Na+-K+-ATPase enzyme activity have been implicated in the development of diabetic complications in animal models of the disease and in humans. The ability of the aldose reductase inhibitor sorbinil to reverse the hyperglycemia-induced changes in these lenticular ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.36.12.1414
更新日期:1987-12-01 00:00:00
abstract::Data based on the prospective study of Job et al. are reanalyzed while initial number of microaneurysms and duration of patient follow-up are controlled. The reported statistical difference in the rate of microaneurysm increase between the single- and the multiple-daily-injection groups may be due to a difference in a...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.27.5.592
更新日期:1978-05-01 00:00:00
abstract::Insulin regulates the rate of expression of many hepatic genes, including PEPCK, glucose-6-phosphatase (G6Pase), and glucose-6-phosphate dehydrogenase (G6PDHase). The expression of these genes is also abnormally regulated in type 2 diabetes. We demonstrate here that treatment of hepatoma cells with 5-aminoimidazole-4-...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.49.6.896
更新日期:2000-06-01 00:00:00
abstract::Obesity is a common problem in Western society and is associated with significant morbidity and mortality. Energy homeostasis is regulated by a complex system involving both peripheral signals such as leptin and a number of orexigenic and anorectic neuropeptides. Obesity can result from dysregulation of the peripheral...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.49.7.1073
更新日期:2000-07-01 00:00:00
abstract::IA-2, a member of the protein tyrosine phosphatase family, represents a major target autoantigen in type 1 diabetes. To study the regulation of IA-2 gene expression, we used INS-1 insulinoma cells to analyze beta-cell signal transduction pathways as well as the effect of metabolic and hormonal factors involved in the ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.49.7.1137
更新日期:2000-07-01 00:00:00
abstract::Low plasma sex hormone-binding globulin (SHBG) levels are associated with obesity and predict the development of type 2 diabetes. The reason why obese individuals have low circulating SHBG has been attributed to hyperinsulinemia, but no mechanistic evidence has been described. The aim of the current study is to explor...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-0727
更新日期:2012-02-01 00:00:00
abstract::Susceptibility of mice to experimental insulin-dependent diabetes as induced by multiple subdiabetogenic doses of streptozotocin has been shown to be strongly gender-dependent, males being much more susceptible than females. We examined this gender difference further in two strains of genetically susceptible mice to d...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.31.8.724
更新日期:1982-08-01 00:00:00
abstract::During the development to overt nephropathy, diabetic patients go through several characteristic stages of renal disease, moving from normo- to micro- to macroalbuminuria. Microalbuminuria is defined as a urinary albumin excretion between 20 and 200 microg/min; values <20 microg/min are designated as normoalbuminuria,...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diab.46.2.s104
更新日期:1997-09-01 00:00:00
abstract::Blood T-cells from 28 patients with type I (insulin-dependent) diabetes (IDDM) of variable duration were examined for the Tac antigen by immunofluorescence, and for proliferation in the presence of interleukin 2 (IL 2). The mean percentage of Tac+ cells in patients whose IDDM was of less than 2-yr duration was 6.2% co...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.33.4.319
更新日期:1984-04-01 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::Spleen cells from conventional BALB/c or athymic mice with streptozotocin (SZ)-induced hyperglycemia failed to raise blood sugar levels when injected into athymic or thymus-sufficient recipients. Passive transfer efforts were unsuccessful despite variations in donor-recipient pairs with respect to age, thymic function...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.29.2.146
更新日期:1980-02-01 00:00:00
abstract::Women gain weight and their diabetes risk increases as they transition through menopause; these changes can be partly reversed by hormone therapy. However, the underlying molecular mechanisms mediating these effects are unknown. A novel knock-in mouse line with the selective blockade of the membrane-initiated estrogen...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db17-1342
更新日期:2018-08-01 00:00:00
abstract::The data being reported are part of an epidemiologic study of health and disease in an entire community, Tecumseh, Michigan. Approximately 1,300 males age 16-65 were classified into three groups on the basis of their habitual leisure and occupational physical activity. A blood sample was drawn one hour after a glucose...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.26.3.172
更新日期:1977-03-01 00:00:00
abstract::Childhood obesity and its comorbidities continue to accelerate across the globe. Two-thirds of pregnant women are obese/overweight, as are 20% of preschoolers. Gestational diabetes mellitus (GDM) is escalating, affecting up to 1 in 5 pregnant women. The field of developmental origins of health and disease has begun to...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/dbi17-0011
更新日期:2018-11-01 00:00:00
abstract::Embryonic stem (ES) cells display the ability to differentiate in vitro into a variety of cell lineages. Using a cell-trapping system, we have obtained an insulin-secreting cell clone from undifferentiated ES cells. The construction used allows the expression of a neomycin selection system under the control of the reg...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.49.2.157
更新日期:2000-02-01 00:00:00
abstract::Insulin receptor substrate (IRS)-1 protein expression is markedly reduced in many insulin-resistant states, although the mechanism for this downregulation is unclear. In this study, we have investigated the early events in the insulin pathway that trigger the degradation of IRS-1. Incubation of the adipocytes with ins...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.50.1.24
更新日期:2001-01-01 00:00:00
abstract::Genes play a role in many processes underlying late diabetic complications, but efforts to identify genetic variants have produced disappointing and contradictory results. Here, we evaluate whether the study designs and analytic methods commonly being used are optimal for finding susceptibility genes for diabetic comp...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diabetes.51.6.1655
更新日期:2002-06-01 00:00:00
abstract::Depletion of cellular antioxidant defense mechanisms and the generation of oxygen free radicals by advanced glycation end products (AGEs) have been proposed to play a major role in the pathogenesis of diabetic vascular complications. Here we demonstrate that incubation of cultured bovine aortic endothelial cells (BAEC...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.46.9.1481
更新日期:1997-09-01 00:00:00