Abstract:
OBJECTIVE:The liver plays a critical role in integrating and controlling glucose metabolism. Thus, it is important that the liver receive and react to signals from other tissues regarding the nutrient status of the body. Leptin, which is produced and secreted from adipose tissue, is a hormone that relays information regarding the status of adipose depots to other parts of the body. Leptin has a profound influence on glucose metabolism, so we sought to determine if leptin may exert this effect in part through the liver. RESEARCH DESIGN AND METHODS:To explore this possibility, we created mice that have disrupted hepatic leptin signaling using a Cre-lox approach and then investigated aspects of glucose metabolism in these animals. RESULTS:The loss of hepatic leptin signaling did not alter body weight, body composition, or blood glucose levels in the mild fasting or random-fed state. However, mice with ablated hepatic leptin signaling had increased lipid accumulation in the liver. Further, as male mice aged or were fed a high-fat diet, the loss of hepatic leptin signaling protected the mice from glucose intolerance. Moreover, the mice displayed increased liver insulin sensitivity and a trend toward enhanced glucose-stimulated plasma insulin levels. Consistent with increased insulin sensitivity, mice with ablated hepatic leptin signaling had increased insulin-stimulated phosphorylation of Akt in the liver. CONCLUSIONS:These data reveal that unlike a complete deficiency of leptin action, which results in impaired glucose homeostasis, disruption of leptin action in the liver alone increases hepatic insulin sensitivity and protects against age- and diet-related glucose intolerance. Thus, leptin appears to act as a negative regulator of insulin action in the liver.
journal_name
Diabetesjournal_title
Diabetesauthors
Huynh FK,Levi J,Denroche HC,Gray SL,Voshol PJ,Neumann UH,Speck M,Chua SC,Covey SD,Kieffer TJdoi
10.2337/db10-0074subject
Has Abstractpub_date
2010-12-01 00:00:00pages
3032-40issue
12eissn
0012-1797issn
1939-327Xpii
db10-0074journal_volume
59pub_type
杂志文章相关文献
DIABETES文献大全abstract::The aim of this study was to test the hypothesis that plasma leptin concentrations contributed to the pathophysiology of NIDDM by decreasing both insulin-mediated glucose disposal and glucose-stimulated insulin secretion. The study was performed in 60 women with normal oral glucose tolerance. Differences in insulin-me...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.47.2.244
更新日期:1998-02-01 00:00:00
abstract::IDDM results from immune-mediated destruction of insulin-producing pancreatic beta-cells in individuals genetically susceptible for the disease. There is evidence that the 65-kDa isoform of GAD plays a critical role in the induction of autoimmune diabetes in NOD mice. In humans, it is still unclear when and to what be...
journal_title:Diabetes
pub_type: 杂志文章,多中心研究
doi:10.2337/diab.45.7.967
更新日期:1996-07-01 00:00:00
abstract::In diabetic patients, elevated plasma levels of t-PA and PAI-1 accompany impaired fibrinolysis. To identify mechanisms for these abnormalities, we examined whether vascular endothelial cells exposed to high glucose upregulate t-PA and PAI-1 production and whether ambient PA activity is decreased concomitantly. In 17 c...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.41.8.1009
更新日期:1992-08-01 00:00:00
abstract::Arterial stiffness affects cardiac functions, peripheral circulation, and cardiovascular mortality. We examined whether arterial stiffness in different regions is equally affected by diabetes and other factors. The subjects were 161 patients with type 2 diabetes and 129 healthy subjects comparable in age and sex. Arte...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.2.448
更新日期:2003-02-01 00:00:00
abstract::A growing body of evidence implicates ceramide and/or its glycosphingolipid metabolites in the pathogenesis of insulin resistance. We have developed a highly specific small molecule inhibitor of glucosylceramide synthase, an enzyme that catalyzes a necessary step in the conversion of ceramide to glycosphingolipids. In...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-1619
更新日期:2007-05-01 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::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::Genetics, epigenetics, and environment may together affect the susceptibility for type 2 diabetes (T2D). Our aim was to dissect molecular mechanisms underlying T2D using genome-wide expression and DNA methylation data in adipose tissue from monozygotic twin pairs discordant for T2D and independent case-control cohorts...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db13-1459
更新日期:2014-09-01 00:00:00
abstract::Vitamin E content and biosynthesis of 12-hydroxyeicosatetraenoic acid (12-HETE) have been measured in platelets from type I diabetic subjects and age- and sex-matched, nondiabetic control subjects. Platelets from diabetic subjects synthesized significantly greater quantities of 12-HETE than did platelets from control ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.34.6.526
更新日期:1985-06-01 00:00:00
abstract::Increased susceptibility of LDL to oxidation has been shown to be associated with the presence of coronary heart disease and may account for the accelerated vascular disease seen in diabetes. The response of LDL to in vitro oxidative stress has been proposed as a measure of the predisposition of LDL to the in vivo sub...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.45.6.762
更新日期:1996-06-01 00:00:00
abstract::Decreased retinal blood flow has been measured in streptozotocin (STZ)-induced diabetes of 1 week's duration, and primary insulin intervention was effective in maintaining normal retinal blood flow in diabetic rats. Retinal blood-flow abnormalities precede clinical diabetic retinopathy in both diabetic animals and pat...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.47.4.653
更新日期:1998-04-01 00:00:00
abstract::Concentrations of glycosylated hemoglobin (GHb) are elevated in diabetes mellitus and are believed to reflect previous metabolic control. To better define possible determinants of GHb in man, we investigated the relationship between GHb and both fasting plasma glucose (FPG) and basal insulin (IRI) in 42 normal subject...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.27.8.834
更新日期:1978-08-01 00:00:00
abstract::Atrasentan, a selective endothelin A receptor antagonist, has been shown to reduce albuminuria in type 2 diabetes. We previously showed that the structural integrity of a glomerular endothelial glycocalyx is required to prevent albuminuria. Therefore we tested the potential of atrasentan to stabilize the endothelial g...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db15-1413
更新日期:2016-08-01 00:00:00
abstract::The macro- and microvascular burden of type 2 diabetes is well established. A number of recent single risk factor intervention trials targeting hyperglycemia, dyslipidemia, hypertension, procoagulation, microalbumuria, and existing cardiovascular disorders have, however, shown major beneficial effects on long-term out...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diabetes.53.suppl_3.s39
更新日期:2004-12-01 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::Isologous pancreatic islets were implanted into the portal vein of rats with streptozotocin-induced diabetes. At intervals of from one to 32 days after transplantation, the intrahepatic islet grafts were examined histologically and ultrastructurally, and their vascular supply was determined by later perfusion studies....
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.26.3.201
更新日期:1977-03-01 00:00:00
abstract::The underlying pathophysiology of the metabolic syndrome is the subject of debate, with both insulin resistance and obesity considered as important factors. We evaluated the differential effects of insulin resistance and central body fat distribution in determining the metabolic syndrome as defined by the National Cho...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.8.2087
更新日期:2004-08-01 00:00:00
abstract::Circulating branched-chain amino acids (BCAAs) associate with insulin resistance and type 2 diabetes. 3-Hydroxyisobutyrate (3-HIB) is a catabolic intermediate of the BCAA valine. In this study, we show that in a cohort of 4,942 men and women, circulating 3-HIB is elevated according to levels of hyperglycemia and estab...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db19-1174
更新日期:2020-09-01 00:00:00
abstract::It is accepted for insulin-secreting cells in culture that the closure of ATP-sensitive K+ channels causes the glucose-dependent depolarization of pancreatic beta-cells seen at subthreshold levels (less than 100 mg/dl) of glucose. The question remains for the more thoroughly studied beta-cells in freshly dissected int...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.38.4.416
更新日期:1989-04-01 00:00:00
abstract::Islets of Langerhans are micro-organs scattered throughout the pancreas that contain insulin-producing cells, called beta-cells. Although new light has been recently shed on beta-cell development, information on the phenotype and location of beta-stem cells remains scarce. Here, we provide evidence that beta-stem cell...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.8.2035
更新日期:2003-08-01 00:00:00
abstract::Coronavirus disease 2019 (COVID-19) is a novel threat that seems to result from the collusion between a new pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and an existing pandemic of metabolic disease driven by obesity. This Perspective explores the evolving epidemiological, clinical, biologi...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/dbi19-0023
更新日期:2020-09-01 00:00:00
abstract:OBJECTIVE:Polymerase I and transcript release factor (PTRF) is a protein highly expressed in adipose tissue and is an integral structural component of caveolae. Here, we report on a novel role of PTRF in lipid mobilization. RESEARCH DESIGN AND METHODS:PTRF expression was examined in different adipose depots of mice du...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db10-0744
更新日期:2011-03-01 00:00:00
abstract::Lifestyle modification reduces the risk of developing type 2 diabetes and may have its effect through improving insulin sensitivity, beta-cell function, or both. To determine whether diet and exercise improve insulin sensitivity and/or beta-cell function and to evaluate these effects over time, we quantified insulin s...
journal_title:Diabetes
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2337/diabetes.54.2.340
更新日期:2005-02-01 00:00:00
abstract::Impaired rate-dependent depression (RDD) of the Hoffman reflex is associated with reduced dorsal spinal cord potassium chloride cotransporter expression and impaired spinal γ-aminobutyric acid type A receptor function, indicative of spinal inhibitory dysfunction. We have investigated the pathogenesis of impaired RDD i...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-1181
更新日期:2017-05-01 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::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::This study examined the role of p38 mitogen-activated protein (MAP) kinase in transducing high glucose into deficits in nerve conduction velocity (NCV) that are characteristic of diabetic neuropathy. p38 activation and NCV were measured in streptozocin-induced diabetic rats treated with a p38 inhibitor, an aldose redu...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.7.1851
更新日期:2004-07-01 00:00:00
abstract::Streptozocin-induced diabetic (STZ-D) mice have reduced brain concentrations of tryptophan, a precursor substance for 5-hydroxytryptamine, and show lengthened immobility in Porsolt's swim test, a putative animal model of depression. This study investigated whether tryptophan affects behavior in Porsolt's swim test in ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.40.12.1598
更新日期:1991-12-01 00:00:00
abstract::The changes in β-cell mass (BCM) during the development and progression of diabetes could potentially be measured by radionuclide imaging using radiolabeled exendin. In this study, we investigated the potential of 111In-diethylenetriaminepentaacetic acid-exendin-3 (111In-exendin) in a rat model that closely mimics the...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db17-1312
更新日期:2018-10-01 00:00:00
abstract:OBJECTIVE:In the present study, we aimed to validate the type 2 diabetes susceptibility alleles identified in six recent genome-wide association studies in the HHEX/KIF11/IDE (rs1111875), CDKN2A/B (rs10811661), and IGF2BP2 (rs4402960) loci, as well as the intergenic rs9300039 variant. Furthermore, we aimed to character...
journal_title:Diabetes
pub_type: 杂志文章,多中心研究
doi:10.2337/db07-0856
更新日期:2007-12-01 00:00:00