Abstract:
:In genetically obese leptin-deficient ob/ob mice, adrenalectomy reverses or attenuates the obese phenotype. Relative to lean controls, ob/ob mice also exhibit decreased hypothalamic proopiomelanocortin (POMC) mRNA and increased hypothalamic agouti-related peptide (AGRP) mRNA and neuropeptide Y (NPY) mRNA. It has been hypothesized that this profile of hypothalamic gene expression contributes to the obese phenotype caused by leptin deficiency. To assess if reversal of obese phenotype by adrenalectomy entails normalization of hypothalamic gene expression, male wild-type and ob/ob mice were adrenalectomized (with saline supplementation) or sham adrenalectomized at 2 months of age. Mice were sacrificed 2 weeks after adrenalectomy, during which time food intake and body weight were monitored daily. After sacrifice, hypothalamic gene expression was assessed by Northern blot analysis as well as in situ hybridization. In wild-type mice, adrenalectomy significantly decreased AGRP mRNA but did not significantly influence POMC or NPY mRNA. In ob/ob mice, adrenalectomy reduced the levels of plasma glucose, serum insulin and corticosterone, and food intake toward or below wild-type levels, and it restored hypothalamic POMC and AGRP mRNA but not NPY mRNA to wild-type levels. These studies suggest that adrenalectomy reverses or attenuates the obese phenotype in ob/ob mice, in part by restoring hypothalamic melanocortin tone toward wild-type levels. These studies also demonstrate that factors other than leptin may play a major role in regulating hypothalamic melanocortin function.
journal_name
Diabetesjournal_title
Diabetesauthors
Makimura H,Mizuno TM,Roberts J,Silverstein J,Beasley J,Mobbs CVdoi
10.2337/diabetes.49.11.1917subject
Has Abstractpub_date
2000-11-01 00:00:00pages
1917-23issue
11eissn
0012-1797issn
1939-327Xjournal_volume
49pub_type
杂志文章相关文献
DIABETES文献大全abstract::In this study we examined the effect of experimental diabetes and of treatment with an aldose reductase inhibitor on the level of sulfation of glomerular basement membrane (GBM) heparan sulfate, the principal glycosaminoglycan in this extracellular matrix. Glycosaminoglycans were isolated from GBM purified from contro...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.37.10.1324
更新日期:1988-10-01 00:00:00
abstract:OBJECTIVE:Common variants in the gene TCF7L2 confer the largest effect on the risk of type 2 diabetes. The present study was undertaken to increase our understanding of the mechanisms by which this gene affects type 2 diabetes risk. RESEARCH DESIGN AND METHODS:Eight subjects with risk-conferring TCF7L2 genotypes (TT o...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-1169
更新日期:2010-02-01 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::Patients with non-insulin-dependent diabetes mellitus (NIDDM) who have chronic hyperglycemia lose acute incremental insulin responses to glucose but are able to briskly respond to other beta-cell secretagogues. To investigate whether this is a defect specific for glucose or represents a more general phenomenon, we mea...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.35.12.1314
更新日期:1986-12-01 00:00:00
abstract::Infection of autoimmune New Zealand mice with the D variant of encephalomyocarditis (EMC) virus results in beta-cell damage and clinical diabetes. The induction of diabetes in parental NZB and NZW strains was independent of sex. However, the susceptibility to virus-induced diabetes in their F1 offspring was sex depend...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.32.8.755
更新日期:1983-08-01 00:00:00
abstract::The glucose-phosphorylating enzyme glucokinase has structural, kinetic, and molecular genetic features that are ideal for its primary role as glucose sensor in a network of neuro/endocrine sentinel cells that maintain glucose homeostasis in many vertebrates including humans. The glucokinase-containing, insulin-produci...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:
更新日期:2006-01-01 00:00:00
abstract::Fetuin-A interferes with insulin action in animal studies, but data on fetuin-A and diabetes risk in humans are sparse and the role of nonalcoholic fatty liver disease in this association is unknown. From 2000 to 2006, we prospectively identified 470 matched incident diabetes case-control pairs in the Nurses' Health S...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db12-0372
更新日期:2013-01-01 00:00:00
abstract::In view of reports that accessory pathways of glucose oxidation are enhanced in the diabetic state, we have determined the levels of key enzymes of the glucuronate-xylulose cycle in the livers of diabetic mice and rats. Genetically diabetic mice (db/db) were found to have increased levels of two NADP-linked enzymes of...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.28.9.793
更新日期:1979-09-01 00:00:00
abstract::Type 1 diabetes (T1D) is an autoimmune disease leading to β-cell destruction. MicroRNAs (miRNAs) are small noncoding RNAs that control gene expression and organ formation. They participate in the pathogenesis of several autoimmune diseases, but the nature of miRNAs contributing to β-cell death in T1D and their target ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-0592
更新日期:2017-01-01 00:00:00
abstract::Representative longitudinal muscle strips (6 x 10 mm) from distal small intestine were obtained from rats after 1, 2, and 3 mo of streptozocin-induced diabetes. The strips were stretched to their optimum lengths and subjected to electrical field stimulation (1-ms pulse duration, 30-270 mA, 10 Hz) in the presence of Kr...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.39.8.891
更新日期:1990-08-01 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::There is evidence from animal models of obesity and type 2 diabetes that increased parasympathetic vagal input to the pancreas contributes to hyperinsulinemia. Compared with Caucasians, Pima Indians have a high risk of type 2 diabetes and exhibit marked hyperinsulinemia and elevated plasma levels of pancreatic polypep...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.3.663
更新日期:2004-03-01 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 effect of cerebral intraventricular insulin on pancreatic insulin secretion was investigated. An extracorporeal pancreatic blood circuit was established after laparotomy to monitor blood flow and insulin concentration directly from the superior pancreaticoduodenal vein. Phentolamine was infused throughout (0.2 mg....
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.24.10.910
更新日期:1975-10-01 00:00:00
abstract::The pancreatic and duodenal homeobox factor-1 (PDX-1), also known as IDX-1/STF-1/IPF1, a homeodomain-containing transcription factor, plays a central role in regulating pancreatic development and insulin gene transcription. Furthermore, even in adults, PDX-1 is associated with islet neogenesis and differentiation of i...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.7.1732
更新日期:2003-07-01 00:00:00
abstract::Single "subdiabetogenic" doses of streptozotocin (SZ), when given to young male CD-1 mice, produced a delayed onset of hyperglycemia dependent on the dose of SZ and on the age of the mice. The effect was markedly reduced or absent in older mice given the same dose of SZ per kg of body weight. Histologic examination of...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.30.9.718
更新日期:1981-09-01 00:00:00
abstract::In peripheral tissues, insulin signaling involves activation of the insulin receptor substrate (IRS)-phosphatidylinositol 3-kinase (PI3K) enzyme system. In the hypothalamus, insulin functions with leptin as an afferent adiposity signal important for the regulation of body fat stores and hepatic glucose metabolism. To ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.2.227
更新日期:2003-02-01 00:00:00
abstract::Enteroviruses have been examined for their possible role in the etiology of IDDM for nearly 40 years, yet the evidence remains inconclusive. The mechanism of acute cytolytic infection of beta-cells, proposed by earlier studies, appears to be incompatible with the long preclinical period of autoimmunity preceding IDDM....
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diab.46.2.161
更新日期:1997-02-01 00:00:00
abstract::A chromosome 1q25 variant (rs10911021) has been associated with coronary heart disease (CHD) in type 2 diabetes. In human umbilical vein endothelial cells (HUVECs), the risk allele "C" is associated with lower expression of the adjacent gene GLUL encoding glutamine synthase, converting glutamic acid to glutamine. To f...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db20-0475
更新日期:2020-10-01 00:00:00
abstract::Hyperglycemia-triggered vascular abnormalities are the most serious complications of diabetes mellitus (DM). The major cause of vascular dysfunction in DM is endothelial injury and dysfunction associated with the reduced number and dysfunction of endothelial progenitor cells (EPCs). A major challenge is to identify ke...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db18-1178
更新日期:2019-08-01 00:00:00
abstract::Toxin from the scorpion Leiurus quinquestriatus was used to release norepinephrine from sympathetic nerve endings in the perfused rat pancrease. Addition of toxin, 10 mug./ml., to perfusate containing 0.3 mg./ml. glucose caused a large increase in release of norepinephrine and glucagon. Glucagon secretion was suppress...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.25.8.645
更新日期:1976-08-01 00:00:00
abstract:OBJECTIVE:ob/ob and db/db mice manifest myocardial hypertrophy, insulin resistance, altered substrate utilization, mitochondrial dysfunction, and lipid accumulation. This study was designed to determine the contribution of central and peripheral leptin signaling to myocardial metabolism and function in ob/ob and db/db ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db10-1106
更新日期:2011-05-01 00:00:00
abstract::Overexpression of hepatocyte growth factor (HGF) in the beta-cell of transgenic mice enhances beta-cell proliferation, survival, and function. In the current studies, we have used conditional ablation of the c-met gene to uncover the physiological role of HGF in beta-cell growth and function. Mice in which c-met is in...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.7.2090
更新日期:2005-07-01 00:00:00
abstract::Cytoplasmic islet cell antibody-negative (ICA-; less than 20 Juvenile Diabetes Foundation units, n = 1670) and ICA+ (n = 42) first-degree relatives of type I (insulin-dependent) diabetic individuals were studied for competitive insulin autoantibodies (CIAAs) with a radioassay. Overall, 3.7% of first-degree relatives (...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.38.10.1320
更新日期:1989-10-01 00:00:00
abstract::Many common genetic polymorphisms are associated with glycemic traits and type 2 diabetes (T2D), but knowledge about genetic determinants of glycemic traits in pregnancy is limited. We tested genetic variants known to be associated with glycemic traits and T2D in the general population for associations with glycemic t...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db18-0203
更新日期:2018-12-01 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::This study addressed the controversial question of whether a negative-insulin-feedback loop exists in vivo. We utilized prehepatic insulin production, calculated by computerized deconvolution analysis of peripheral C-peptide concentration, as a measure of endogenous insulin secretion. Prehepatic insulin production was...
journal_title:Diabetes
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2337/diab.36.8.959
更新日期:1987-08-01 00:00:00
abstract::Adiponectin is an adipose tissue-specific protein with insulin-sensitizing and antiatherogenic properties. Therefore, the adiponectin gene is a promising candidate gene for type 2 diabetes. We investigated the single nucleotide polymorphisms (SNPs) +45T/G and +276G/T of the adiponectin gene as predictors for the conve...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.3.893
更新日期:2005-03-01 00:00:00
abstract:OBJECTIVE:IKZF1 encoding Ikaros, an essential regulator of lymphopoiesis and immune homeostasis, has been implicated in the development of childhood acute lymphoblastic leukemia (C-ALL). Because recent genome-wide association (GWA) studies have linked a region of the 3'-UTR of IKZF1 with C-ALL susceptibility, we tested...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db10-0446
更新日期:2011-03-01 00:00:00
abstract::We examined the effects of high-dosage vitamin E treatment over a 12-month period on the vascular reactivity of micro- and macrocirculation and left ventricular function in diabetic patients. Subjects (n = 89) were randomized to vitamin E (1,800 IU daily) or placebo and were followed for 12 months. High-resolution ult...
journal_title:Diabetes
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2337/diabetes.54.1.204
更新日期:2005-01-01 00:00:00