Abstract:
:We have shown previously that palmitate treatment of C2C12 skeletal muscle myotubes causes inhibition of the protein kinase B (PKB) pathway and hence reduces insulin-stimulated glycogen synthesis through the elevation of intracellular ceramide levels. Ceramide is known to activate both atypical protein kinase C (aPKC) zeta and protein phosphatase (PP) 2A, and each of these effectors has been reported to inhibit PKB. In the present study, palmitate pretreatment was found to elevate PP2A-like activity in myotubes and to prevent its inhibition by insulin. Incubation with the phosphatase inhibitor okadaic acid before insulin stimulation protected against the effect of the fatty acid on PKB phosphorylation. Palmitate was unable to inhibit PKB activity and glycogen synthesis in cells overexpressing the activated PKB mutant (T308D,S473D)-PKBalpha, which is unaffected by phosphatase. In contrast, PKB activity and glycogen synthesis were still inhibited by palmitate in cells overexpressing a membrane-targeted and, hence, activated PKB mutant that retains sensitivity to phosphatase. Although aPKC activity was also increased in palmitate-treated cells, overexpression of wild-type or kinase-dead aPKCzeta did not alter the inhibitory effects of the lipid on either stimulation of PKB or glycogen synthesis by insulin. We conclude that palmitate disrupts insulin signaling in C2C12 myotubes by promoting PP2A-like activity and, therefore, the dephosphorylation of PKB, which in turn reduces the stimulation of glycogen synthesis.
journal_name
Diabetesjournal_title
Diabetesauthors
Cazzolli R,Carpenter L,Biden TJ,Schmitz-Peiffer Cdoi
10.2337/diabetes.50.10.2210subject
Has Abstractpub_date
2001-10-01 00:00:00pages
2210-8issue
10eissn
0012-1797issn
1939-327Xjournal_volume
50pub_type
杂志文章相关文献
DIABETES文献大全abstract::Understanding and manipulating pancreatic beta-cell proliferation is a major challenge for pancreas biology and diabetes therapy. Recent studies have raised the possibility that human beta-cells can undergo dedifferentiation and give rise to highly proliferative mesenchymal cells, which retain the potential to rediffe...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-1654
更新日期:2007-05-01 00:00:00
abstract::In early 1988, a colony of GK rats was started in Paris with progenitors issued from F35 of the original colony reported by Goto and Kakisaki. When studied longitudinally up to 8 mo, GK rats showed as early as 1 mo (weaning) significantly higher basal plasma glucose (9 mM) and insulin levels (doubled), altered glucose...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.40.4.486
更新日期:1991-04-01 00:00:00
abstract::Considerable evidence implicates cellular senescence in the biology of aging and chronic disease. Diet and exercise are determinants of healthy aging; however, the extent to which they affect the behavior and accretion of senescent cells within distinct tissues is not clear. Here we tested the hypothesis that exercise...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db15-0291
更新日期:2016-06-01 00:00:00
abstract::Highly angiogenic bone marrow mononuclear cell-derived spheroids (BM-spheroids), formed by selective proliferation of the CD31+CD14+CD34+ monocyte subset via three-dimensional (3D) culture, have had robust angiogenetic capacity in rodent syngeneic renal subcapsular islet transplantation. We wondered whether the effica...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db17-0705
更新日期:2018-03-01 00:00:00
abstract:OBJECTIVE:Obesity-associated insulin resistance is characterized by a state of chronic, low-grade inflammation that is associated with the accumulation of M1 proinflammatory macrophages in adipose tissue. Although different evidence explains the mechanisms linking the expansion of adipose tissue and adipose tissue macr...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db10-0705
更新日期:2011-03-01 00:00:00
abstract:OBJECTIVE:To assess chemerin levels and regulation in sera and adipose tissue from women with polycystic ovary syndrome (PCOS) and matched control subjects. RESEARCH DESIGN AND METHODS:Real-time RT-PCR and Western blotting were used to assess mRNA and protein expression of chemerin. Serum chemerin was measured by enzy...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db08-1528
更新日期:2009-09-01 00:00:00
abstract::Spirometry was performed on 88 children with insulin-dependent diabetes mellitus (IDDM) and 216 healthy controls living in Sheffield. Children with IDDM had significantly lower percentage predicted forced vital capacity (FVC) than did control children or reference norms. There was no evidence that the reduced FVC was ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.36.3.324
更新日期:1987-03-01 00:00:00
abstract::Islet transplantation is a potential treatment for type 1 diabetes, but the shortage of donor organs limits its routine application. As potential donor animals, we generated transgenic pigs expressing LEA29Y, a high-affinity variant of the T-cell costimulation inhibitor CTLA-4Ig, under the control of the porcine insul...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-1325
更新日期:2012-06-01 00:00:00
abstract::Tolbutamide (1 g/kg body wt) was administered to male rats for 3 days to determine the effects of this pretreatment on subsequent insulin biosynthesis and compartmental storage characteristics of freshly isolated islets. Islets were isolated 16 h after the last tolbutamide administration, at a time when fed plasma glu...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.35.1.6
更新日期:1986-01-01 00:00:00
abstract::Leptin, the product of the OB gene, is increased in obese individuals, suggesting resistance to its effect. We questioned whether subjects with NIDDM have an altered regulation of serum leptin levels. We used a radioimmunoassay to measure serum leptin levels in three groups from the San Antonio Heart Study: 1) 50 Mexi...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.45.6.822
更新日期:1996-06-01 00:00:00
abstract::Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) often coexist and as such represent a potent risk factor for subsequent development of type 2 diabetes. beta-Cell mass is approximately 50% deficient in IFG and approximately 65% deficient in type 2 diabetes. To establish the effect of a approximately...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-0345
更新日期:2006-08-01 00:00:00
abstract::Different degrees of beta-cell failure and apoptosis are present in type 1 and type 2 diabetes. It has been recently suggested that high glucose-induced beta-cell apoptosis in type 2 diabetes shares a final common pathway with type 1 diabetes, involving interleukin-1beta (IL-1beta) production by beta-cells, nuclear fa...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.11.3238
更新日期:2005-11-01 00:00:00
abstract:OBJECTIVE:The aim of this analysis was to assess the prospective association of serum testosterone and dehydroepiandrosterone sulfate (DHEAS) levels with incident metabolic syndrome (MetS) in men. RESEARCH DESIGN AND METHODS:Data were obtained from the Study of Health in Pomerania (SHIP), a population-based prospectiv...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-0031
更新日期:2009-09-01 00:00:00
abstract::We studied certain metabolic requirements for insulin-induced increases in phospholipids, and the relationship of phospholipid changes to the insulin-induced activation of pyruvate dehydrogenase, in rat adipocytes and fat pads in vitro. Increases in the contents of phosphatidylinositol and phosphatidylserine mass were...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.33.7.648
更新日期:1984-07-01 00:00:00
abstract::Accumulation of triosephosphates arising from high cytosolic glucose concentrations in hyperglycemia is the trigger for biochemical dysfunction leading to the development of diabetic nephropathy-a common complication of diabetes associated with a high risk of cardiovascular disease and mortality. Here we report that s...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.8.2110
更新日期:2003-08-01 00:00:00
abstract::Ghrelin, an endogenous ligand for growth hormone secretagogue (GHS) receptor originally isolated from the stomach, occurs in the hypothalamic arcuate nucleus and may play a role in energy homeostasis. Synthetic GHSs have activated the hypothalamic arcuate neurons containing neuropeptide Y (NPY), suggesting the involve...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.50.2.227
更新日期:2001-02-01 00:00:00
abstract::Patients with long-standing type 1 diabetes (T1D) may exhibit defective glucose counterregulation and impaired hypoglycemia symptom recognition that substantially increase their risk for experiencing severe hypoglycemia. The purpose of this study was to determine whether intrahepatic islet transplantation improves end...
journal_title:Diabetes
pub_type: 临床试验,杂志文章
doi:10.2337/db14-1620
更新日期:2015-05-01 00:00:00
abstract::Orexins (hypocretins) are novel neuropeptides that appear to play a role in the regulation of energy balances. Orexin-A (OXA) increases food intake in rodents, and fasting activates OXA neurons in both the lateral hypothalamic area and gut. OXA is also found in the endocrine pancreas; however, little is known about it...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.1.111
更新日期:2003-01-01 00:00:00
abstract::Both insulin resistance and decreased insulin secretion have been hypothesized to be precursors of non-insulin-dependent diabetes. An elevated proinsulin concentration reflects abnormal proinsulin processing and could indicate abnormal insulin secretion. We examined fasting insulin (measured by a radioimmunoassay that...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.44.10.1156
更新日期:1995-10-01 00:00:00
abstract::Tissue sensitivity to insulin was studied using the euglycemic insulin clamp technique (delta plasma insulin above basal 90 microU/ml) in eight patients with type I diabetes mellitus (IDDM) before and after 4-8 mo of continuous subcutaneous insulin infusion (CSII) and in 36 age-matched control subjects. Institution of...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.34.3.s80
更新日期:1985-08-01 00:00:00
abstract::Plasma phospholipid transfer protein (PLTP) plays an important role in lipoprotein metabolism. PLTP activity is elevated in patients with diabetes, a condition with strongly elevated risk for coronary heart disease. The aim of this study was to test the hypothesis that statins reduce PLTP activity and to examine the p...
journal_title:Diabetes
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.2337/db05-1685
更新日期:2006-05-01 00:00:00
abstract::The current view of diabetic kidney disease, based on meticulously acquired ultrastructural morphometry and the utility of measuring plasma creatinine and urinary albumin, has been almost entirely focused on the glomerulus. While clearly of great importance, changes in the glomerulus are not the major determinant of r...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/db16-0796
更新日期:2017-04-01 00:00:00
abstract::The high-mobility group box transcription factor SOX4 is the most highly expressed SOX family protein in pancreatic islets, and mutations in Sox4 are associated with an increased risk of developing type 2 diabetes. We used an inducible β-cell knockout mouse model to test the hypothesis that Sox4 is essential for the m...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-1074
更新日期:2017-08-01 00:00:00
abstract::The selective impairment of glucose-induced insulin secretion in NIDDM can be attributed to defects in the glucose-signaling system. An alteration in the activity of phosphofructokinase (PFK), a key enzyme in the glycolytic pathway, may play a role in the abnormal glucose-induced insulin secretion. In this study, we e...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.46.9.1414
更新日期:1997-09-01 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::A patient with functioning islet cell carcinoma is described who had amelioration of her hypoglycemia during the development of ectopic ACTH syndrome. Moon facies and hyperkalemic metabolic acidosis were also present in this patient, features uncommonly seen in the actopic ACTH syndrome. At autopsy, she was found to h...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.24.6.600
更新日期:1975-06-01 00:00:00
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::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::Altered proteoglycan metabolism may play a role in the development of diabetic glomerulopathy. This study was conducted to examine the effects of glucose on the production and physical characteristics of proteoglycans generated by rat mesangial cells in culture. Rat mesangial cells were exposed to elevated glucose med...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.42.12.1815
更新日期:1993-12-01 00:00:00
abstract::Neonatal rats injected with streptozocin (STZ, 100 mg/kg) at birth exhibited an acute diabetes followed by a spontaneous remission. We have previously shown that this recovery from neonatal diabetes is due to B-cell regeneration and reaccumulation of pancreatic insulin stores starting from 3 to 5 days after birth. The...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.34.6.574
更新日期:1985-06-01 00:00:00