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 mice featured increased lipogenic gene expression in the liver and adipose tissue. Their selective, liver-specific insulin resistance was associated with increased C18:1-diacylglycerol content and protein kinase Cε translocation. SEC mice had decreased lipogenesis mediated by hepatic cholesterol responsive element-binding protein and featured portal/lobular inflammation along with total, whole-body insulin resistance. Hepatic mitochondrial respiration transiently increased and declined with aging along with higher muscle reactive oxygen species production. In conclusion, hepatic insulin resistance originates from lipotoxicity but not from lower mitochondrial capacity, which can even transiently adapt to increased peripheral lipolysis. Peripheral insulin resistance is prevented during increased hepatic lipogenesis only if adipose tissue lipid storage capacity is preserved.
journal_name
Diabetesjournal_title
Diabetesauthors
Jelenik T,Kaul K,Séquaris G,Flögel U,Phielix E,Kotzka J,Knebel B,Fahlbusch P,Hörbelt T,Lehr S,Reinbeck AL,Müller-Wieland D,Esposito I,Shulman GI,Szendroedi J,Roden Mdoi
10.2337/db16-1147subject
Has Abstractpub_date
2017-08-01 00:00:00pages
2241-2253issue
8eissn
0012-1797issn
1939-327Xpii
db16-1147journal_volume
66pub_type
杂志文章相关文献
DIABETES文献大全abstract:OBJECTIVE:C57Bl/6 mice develop obesity and mild hyperglycemia when fed a high-fat diet (HFD). Although diet-induced obesity (DIO) is a widely studied model of type 2 diabetes, little is known about beta-cell failure in these mice. RESEARCH DESIGN AND METHODS:DIO mice were separated in two groups according to body weig...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-1452
更新日期:2010-09-01 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::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::We recently showed that a peptide of the M(r) 60,000 heat shock protein molecule, designated peptide p277, is a target of T-cells in autoimmune diabetes in NOD mice. Indeed, the p277 peptide could be used as a therapeutic agent to arrest the autoimmune process even after it was far advanced. The present study was done...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.44.9.1132
更新日期:1995-09-01 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::Growth differentiation factor 11 (GDF11) has been shown to promote stem cell activity and rejuvenate the function of multiple organs in old mice, but little is known about the functions of GDF11 in the diabetic rat model of hindlimb ischemia. In this study, we found that systematic replenishment of GDF11 rescues angio...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db17-1583
更新日期:2018-10-01 00:00:00
abstract::To determine the role of prolactin in increasing junctional communication among islet beta-cells, we studied dye coupling in pancreatic islets exposed to elevated levels of prolactin in vivo and in vitro. Islets were isolated from rats immediately after lactation or from rats bearing mammosomatotropic tumors (MtTW15),...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.36.10.1098
更新日期:1987-10-01 00:00:00
abstract::In humans, the glucagon response to moderate-to-marked insulin-induced hypoglycemia (IIH) is largely mediated by the autonomic nervous system. Because this glucagon response is impaired early in type 1 diabetes, we sought to determine if these patients, like animal models of autoimmune diabetes, have an early and seve...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-0284
更新日期:2016-08-01 00:00:00
abstract::Pulsatile insulin secretion in vivo is believed to be derived, in part, from the intrinsic glucose-dependent intracellular calcium concentration ([Ca2+]i) pulsatility of individual islets. In isolation, islets display fast, slow, or mixtures of fast and slow [Ca2+]i oscillations. We show that the period of islet [Ca2+...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.12.3517
更新日期:2005-12-01 00:00:00
abstract::Subjects with low serum HDL cholesterol levels are reported to be susceptible to diabetes, with insulin resistance believed to be the underlying pathological mechanism. Apolipoprotein M (apoM) is a carrier of sphingosine-1-phosphate (S1P), a multifunctional lipid mediator, on HDL, and the pleiotropic effects of HDL ar...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db19-0811
更新日期:2020-05-01 00:00:00
abstract::The past decade has witnessed an exponential increase in our ability to search the genome for genetic factors predisposing to cardiovascular disease (CVD) and in particular coronary heart disease (CHD). Identifying these genes could lead to the development of innovative strategies to prevent the cardiovascular complic...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/dbi18-0036
更新日期:2019-03-01 00:00:00
abstract::I investigated biochemical parameters of sympathetic nerve function in spontaneously diabetic mice(C57 BL/KsJdb/db) and in their lean littermates. The concentration of norepinephrine (NE) in organs innervated by sympathetic nerves was significantly reduced in the heart, kidney, and salivary glands of mice (24 weeks ol...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.27.10.969
更新日期:1978-10-01 00:00:00
abstract::Autoantibodies to glutamic acid decarboxylase (GAD) are frequent at or before the onset of insulin-dependent diabetes mellitus (IDDM). We have developed a simple, reproducible, and quantitative immunoprecipitation radioligand assay using as antigen in vitro transcribed and translated [35S]methionine-labeled human isle...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.43.3.459
更新日期:1994-03-01 00:00:00
abstract::Obesity and type 2 diabetes are associated with impaired mitochondrial function in adipose tissue. To study the effects of primary deficiency of mitochondrial energy metabolism in fat, we generated mice with adipose-specific deficiency of fumarate hydratase (FH), an integral Krebs cycle enzyme (AFHKO mice). AFHKO mice...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-0136
更新日期:2016-11-01 00:00:00
abstract::Recent data have suggested a key role for tumor necrosis factor (TNF)-alpha in the insulin resistance of obesity and non-insulin-dependent diabetes mellitus (NIDDM). TNF-alpha expression is elevated in the adipose tissue of multiple experimental models of obesity. Neutralization of TNF-alpha in one of these models imp...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diab.43.11.1271
更新日期:1994-11-01 00:00:00
abstract::In 112 obese compared with 42 lean children, we found that serum leptin is elevated early in the evolution of childhood-onset obesity (28.4 +/- 1.4 vs. 4.5 +/- 0.4 ng/ml in lean children, P < 0.0001) and correlates with adiposity. Obese children also had higher serum leptin normalized to fat mass. Despite high serum l...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.46.6.989
更新日期:1997-06-01 00:00:00
abstract::Although type 1 diabetes (T1D) is primarily perceived as a T cell-driven autoimmune disease, islet autoantibodies are the best currently available biomarker for autoimmunity and disease risk. These antibodies are produced by autoreactive B cells, the activation of which is largely dependent on the function of CD4+CXCR...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-0714
更新日期:2017-02-01 00:00:00
abstract::Hypoglycemia limits optimal glycemic control in type 1 diabetes mellitus (T1DM), making novel strategies to mitigate it desirable. We hypothesized that portal (Po) vein insulin delivery would lessen hypoglycemia. In the conscious dog, insulin was infused into the hepatic Po vein or a peripheral (Pe) vein at a rate fou...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db15-0071
更新日期:2015-10-01 00:00:00
abstract::We tested the hypothesis that dysfunction of vascular endothelium, indicated by an increase in plasma level of von Willebrand factor (vWF), is present in patients with insulin-dependent diabetes mellitus (IDDM) who develop diabetic nephropathy (DN). DN was classified as absent (urinary albumin excretion [UAE] rate les...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.40.8.971
更新日期:1991-08-01 00:00:00
abstract::Fourteen rats of the spontaneously diabetic BB line were bled from the retroorbital sinus approximately every 10 days. Sera taken from an early age up to 20 days after the onset of overt diabetes were assayed for complement-fixing antibodies against antigens of the surface of islet cells (CFA). Dispersed islet cells f...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.33.1.93
更新日期:1984-01-01 00:00:00
abstract::Class IIa histone deacetylases (HDACs), such as HDAC4, HDAC5, and HDAC7, provide critical mechanisms for regulating glucose homeostasis. Here we report that HDAC9, another class IIa HDAC, regulates hepatic gluconeogenesis via deacetylation of a Forkhead box O (FoxO) family transcription factor, FoxO1, together with HD...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db15-0197
更新日期:2015-12-01 00:00:00
abstract::Hypoglycemia causes substantial morbidity and some mortality in insulin-dependent diabetes mellitus (IDDM). It is often the limiting factor in attempts to achieve euglycemia. The prevention or correction of hypoglycemia normally involves both dissipation of insulin and activation of glucose counterregulatory systems. ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.38.9.1193
更新日期:1989-09-01 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::Successful islet transplantation depends on the infusion of sufficiently large quantities of islets, but only a fraction of transplanted islets can survive and become engrafted, and yet the underlying mechanism remains unclear. In this study, we examined the effect of sirolimus, a key component of the immunosuppressiv...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-0173
更新日期:2006-09-01 00:00:00
abstract::Decreased uncoupling protein (UCP)3 is associated with insulin resistance in muscle of pre-diabetic and diabetic individuals, but the function of UCP3 remains unclear. Our goal was to elucidate mechanisms underlying the negative correlation between UCP3 and insulin resistance in muscle. We determined effects of physio...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.8.2343
更新日期:2005-08-01 00:00:00
abstract::Type 2 diabetes (T2D) is associated with vascular dysfunction. We hypothesized that increased nuclear factor-κB (NF-κB) signaling contributes to vascular dysfunction in T2D. We treated type 2 diabetic (db(-)/db(-)) and control (db(-)/db(+)) mice with two NF-κB inhibitors (6 mg/kg dehydroxymethylepoxyquinomicin twice a...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db12-1374
更新日期:2013-06-01 00:00:00
abstract:OBJECTIVE:Glucagon-like peptide-1 receptor (GLP-1R) agonists are used to treat type 2 diabetes, and transient GLP-1 administration improved cardiac function in humans after acute myocardial infarction (MI) and percutaneous revascularization. However, the consequences of GLP-1R activation before ischemic myocardial inju...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db08-1193
更新日期:2009-04-01 00:00:00
abstract::Key parameters of the endocrine pancreas, such as islet number, islet mass, beta-cell mass, and alpha-cell mass, were studied in different strains of inbred mice to investigate the impact of genetic background on the size and structure of the endocrine pancreas. Six mice from each of seven different strains of inbred ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.1.133
更新日期:2005-01-01 00:00:00
abstract::The association between clinical autonomic dysfunction and myocardial MIBG accumulation was investigated. The study groups comprised 6 male diabetic patients with autonomic neuropathy (ANP+ group), 6 male diabetic patients without autonomic neuropathy (ANP-group), and 6 male nondiabetic control subjects. The mean age ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.41.9.1069
更新日期:1992-09-01 00:00:00
abstract::The use of HIV protease inhibitors (PIs) has been associated with several metabolic changes, including lipodystrophy, hyperlipidemia, and insulin resistance. The etiology of these adverse effects remains unknown. PIs have recently been found to cause acute and reversible inhibition of GLUT4 activity in vitro. To deter...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.4.937
更新日期:2002-04-01 00:00:00