Abstract:
:Insulin and exercise stimulate glucose uptake into skeletal muscle via different pathways. Both stimuli converge on the translocation of the glucose transporter GLUT4 from intracellular vesicles to the cell surface. Two Rab guanosine triphosphatases-activating proteins (GAPs) have been implicated in this process: AS160 for insulin stimulation and its homolog, TBC1D1, are suggested to regulate exercise-mediated glucose uptake into muscle. TBC1D1 has also been implicated in obesity in humans and mice. We investigated the role of TBC1D1 in glucose metabolism by generating TBC1D1(-/-) mice and analyzing body weight, insulin action, and exercise. TBC1D1(-/-) mice showed normal glucose and insulin tolerance, with no difference in body weight compared with wild-type littermates. GLUT4 protein levels were reduced by ∼40% in white TBC1D1(-/-) muscle, and TBC1D1(-/-) mice showed impaired exercise endurance together with impaired exercise-mediated 2-deoxyglucose uptake into white but not red muscles. These findings indicate that the RabGAP TBC1D1 plays a key role in regulating GLUT4 protein levels and in exercise-mediated glucose uptake in nonoxidative muscle fibers.
journal_name
Diabetesjournal_title
Diabetesauthors
Stöckli J,Meoli CC,Hoffman NJ,Fazakerley DJ,Pant H,Cleasby ME,Ma X,Kleinert M,Brandon AE,Lopez JA,Cooney GJ,James DEdoi
10.2337/db13-1489subject
Has Abstractpub_date
2015-06-01 00:00:00pages
1914-22issue
6eissn
0012-1797issn
1939-327Xpii
db13-1489journal_volume
64pub_type
杂志文章相关文献
DIABETES文献大全abstract::Fibroblast growth factor 21 (FGF21) is increasingly recognized as an important metabolic regulator of glucose homeostasis. Here, we conducted an exome-chip association analysis by genotyping 5,169 Chinese individuals from a community-based cohort and two clinic-based cohorts. A custom Asian exome-chip was used to dete...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-1384
更新日期:2017-06-01 00:00:00
abstract::To treat insulin lipoatrophy, small amounts of dexamethasone (4 micrograms/unit) were added to insulin injections in nine patients. Six cases showed significant improvement of dexamethasone-treated sites over that of control sites in six months. With the continued use of dexamethasone-containing insulin, they remained...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.26.4.296
更新日期:1977-04-01 00:00:00
abstract::RIN-m cells, cultured from a rat insulinoma, not only bind and secrete but also degrade insulin (Diabetes 1982; 31:521-31). The insulin-degrading activity resides in the cytosol and is similar to the insulin-specific proteases previously described in muscle and other tissues. It has an apparent Km of 0.15 microM for p...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.34.2.121
更新日期:1985-02-01 00:00:00
abstract::Activation of AMPK suppresses inflammation, but the underlying mechanisms remain poorly understood. This study was designed to characterize the molecular mechanisms by which AMPK suppresses vascular inflammation. In cultured human aortic smooth muscle cells, pharmacologic or genetic activation of AMPK inhibited the si...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db15-0107
更新日期:2015-12-01 00:00:00
abstract::Nonalcoholic fatty liver disease is associated with hepatic insulin resistance and may result primarily from increased hepatic de novo lipogenesis (PRIM) or secondarily from adipose tissue lipolysis (SEC). We studied mice with hepatocyte- or adipocyte-specific SREBP-1c overexpression as models of PRIM and SEC. PRIM mi...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-1147
更新日期:2017-08-01 00:00:00
abstract::The effects on N-acetylheparosan deacetylase (N-deacetylase) activity exerted by poorly and well-regulated diabetes and variation of genetic background were investigated in insulin-treated streptozocin-induced diabetic rats of two different strains (H and U). N-deacetylase plays a key role in heparan sulfate biosynthe...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.40.11.1449
更新日期:1991-11-01 00:00:00
abstract::Counterregulatory hormonal responses were studied in six patients after 4-18 mo treatment with a continuous subcutaneous insulin infusion pump. In response to insulin-induced hypoglycemia, significant increases in epinephrine, norepinephrine, cortisol, and growth hormone were measured in all subjects, while in five of...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.32.5.398
更新日期:1983-05-01 00:00:00
abstract::At rest and during exercise, chronic hyperglycemia, high free fatty acid (FFA) oxidation, and insulin deficiency in diabetes are well known to impair glucose clearance (metabolic clearance rate [MCR]). The effect of acute restoration of glycemia per se on MCR has been less well characterized. We therefore studied norm...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.46.11.1805
更新日期:1997-11-01 00:00:00
abstract::The pretreatment of isolated islets of Langerhans with concanavalin A (Con A) completely blocks alloxan from suppressing the insulin release response to glucose. The lectin itself inhibits insulin secretion. This effect is dose dependent and reversible. Con A, however, has no protective action against the inhibition o...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.33.2.164
更新日期:1984-02-01 00:00:00
abstract::Rats with classic Goldblatt (two-kidney) hypertension had diabetes induced by streptozotocin. After four months of diabetes, glomeruli of the unclipped kidney of hypertensive diabetic rats had markedly increased diabetic changes, including mesangial matrix thickening and mesangial immunoglobulin (IgG and IgM) and comp...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.27.7.738
更新日期:1978-07-01 00:00:00
abstract::p21(cip1), a regulatory molecule upstream of the G(1/0) checkpoint, is increased in beta-cells in response to mitogenic stimulation. Whereas p21(cip1) can variably stimulate or inhibit cell cycle progression, in vitro studies suggest that p21(cip1) acts as an inhibitor in the pancreatic beta-cell. To determine the fun...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-0627
更新日期:2006-12-01 00:00:00
abstract::Adiponectin, an adipocyte protein important in insulin sensitization and cardioprotection, has a strong genetic component. We hypothesized that variants in the adiponectin gene (adipocyte collagen-domain containing [ACDC]) contribute to adiponectin levels in a biracial adolescent cohort. We genotyped 11 ACDC single nu...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.55.02.06.db05-0446
更新日期:2006-02-01 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::Diabetes-induced oxidative stress can lead to protein misfolding and degradation by the ubiquitin-proteasome system. This study examined protein ubiquitination in pancreatic sections from Zucker diabetic fatty rats. We observed large aggregates of ubiquitinated proteins (Ub-proteins) in insulin-expressing beta-cells a...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-1160
更新日期:2007-04-01 00:00:00
abstract::The effects of oral vanadate supplementation on intestinal morphometry and glucose transport were examined in STZ-induced diabetic and age-matched control male Sprague-Dawley rats. Animals received 0.1 mg/ml vanadium pentoxide in their drinking water over 14 days. Vanadate reduced intestinal glucose maximal transport ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.42.8.1126
更新日期:1993-08-01 00:00:00
abstract::NO has been identified recently as the prime islet-toxic product of inflammatory macrophages. The adverse effects of IL-1 on isolated islets also have been reported to involve NO. We now show that exposure of an islet cell suspension to the NO donor nitroprusside or to activated macrophages leads to DNA strand breaks....
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.42.3.496
更新日期:1993-03-01 00:00:00
abstract::We have recently demonstrated that the exposure to hyperglycemia in utero impairs nephrogenesis in rat fetuses (Amri K et al., Diabetes 48:2240-2245, 1999). Diabetic pregnancy is commonly associated with alterations in the IGF system in fetal tissues. It has also been shown that both IGF-I and IGF-II are produced with...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.50.5.1069
更新日期:2001-05-01 00:00:00
abstract::The development of autoimmune diabetes in NOD mice results from selective destruction of beta-cells by a T-cell-dependent autoimmune process. However, the mechanisms that control the generation of beta-cell cytotoxic T-cells in vivo are poorly understood. We recently established 8.3-T-cell receptor (TCR)-beta transgen...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.1.34
更新日期:1999-01-01 00:00:00
abstract::The clinical features of the experimental hyperosmolar diabetic (EHD) rat model resemble those seen in the human syndrome--extreme hyperglycemia without ketoacidosis is common to both. The absence of ketoacidosis in the syndrome has been ascribed to both substrate (free fatty acid) deficiency and to interference with ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.24.3.301
更新日期:1975-03-01 00:00:00
abstract::We have biochemically treated (periodate, borohydride, neuraminidase, organic solvents) frozen sections of human pancreas and studied the reactivity of islet-cell-antibody-positive human sera and monoclonal antibodies. The autoantigen of pancreatic sections has the properties of sialic acid containing glycolipid. ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.34.6.617
更新日期:1985-06-01 00:00:00
abstract:OBJECTIVE:MBL2 encodes the mannose-binding lectin, which is a key player in the innate immune system and has recently been found to play a role in insulin resistance and development of type 1 diabetes and gestational diabetes mellitus. To assess the role of MBL2 in diabetes susceptibility, this gene was analyzed in the...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-1593
更新日期:2010-08-01 00:00:00
abstract::Although epinephrine stimulates insulin release by activation of beta-adrenergic receptors, its dominant effect (mediated by stimulation of alpha-adrenergic receptors) is an inhibition of insulin secretion that is powerful enough to suppress the secretory activity of insulin's most potent stimulants. The insulin-secre...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.27.5.550
更新日期:1978-05-01 00:00:00
abstract::Substantial progress has been made in identification of type 2 diabetes (T2D) risk loci in the past few years, but our understanding of the genetic basis of T2D in ethnically diverse populations remains limited. We performed a genome-wide association study and a replication study in Chinese Hans comprising 8,569 T2D c...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db12-0454
更新日期:2013-01-01 00:00:00
abstract:OBJECTIVE:Klotho is an antiaging hormone present in the kidney that extends the lifespan, regulates kidney function, and modulates cellular responses to oxidative stress. We investigated whether Klotho levels and signaling modulate inflammation in diabetic kidneys. RESEARCH DESIGN AND METHODS:Renal Klotho expression w...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db10-1262
更新日期:2011-07-01 00:00:00
abstract::Studies have shown associations between exposure to hypoglycemia and increased mortality, raising the possibility that hypoglycemia has adverse cardiovascular effects. In this study, we determined the acute effects of hypoglycemia on cardiovascular autonomic control. Seventeen healthy volunteers were exposed to experi...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db15-0871
更新日期:2016-01-01 00:00:00
abstract::Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) has been implicated in the control of blood glucose by its potent effect on expression and signaling of various nuclear receptors. To understand the role of COUP-TFII in glucose homeostasis, conditional COUP-TFII-deficient mice were generated and ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.5.1357
更新日期:2005-05-01 00:00:00
abstract::The last two decades have witnessed an explosion of interest in adipocyte biology, coinciding with the upsurge of obesity and metabolic syndrome. Now we have new perspectives on the distinct developmental origins of white, brown, and beige adipocytes and their role in metabolic physiology and disease. Beyond fuel meta...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/dbi18-0009
更新日期:2019-05-01 00:00:00
abstract::Determinants of proliferative diabetic retinopathy (PDR) that occur during the 2nd decade of insulin-dependent diabetes mellitus (IDDM) (early-onset PDR) were investigated in a nested case-control study. From an inception cohort of patients with juvenile-onset IDDM that now has 15-21 yr diabetes duration, the patients...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.41.4.430
更新日期:1992-04-01 00:00:00
abstract::A recent study has demonstrated secondary amyloidosis in dogs treated with continuous intravenous insulin infusion. Since elevated levels of serum amyloid A protein (SAA) and diminished amyloid fibril degrading activity (AFDA) are associated with amyloidosis, we measured SAA and AFDA in ten type I diabetics treated wi...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.32.1.88
更新日期:1983-01-01 00:00:00
abstract:OBJECTIVE:We hypothesized that intranasal insulin (I-I) delivery targets the nervous system while avoiding potential adverse systemic effects when compared with subcutaneous insulin (S-I) for experimental streptozotocin-induced diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS:I-I or S-I at 0.87 IU dai...
journal_title:Diabetes
pub_type: 杂志文章,收录出版
doi:10.2337/db08-1287
更新日期:2009-04-01 00:00:00