Identification and saturable nature of signaling pathways induced by metreleptin in humans: comparative evaluation of in vivo, ex vivo, and in vitro administration.

abstract：:This study investigated changes in levels of mRNAs encoding the three neurofilament (NF) proteins NF-L (low), NF-M (medium), and NF-H (high) and two growth-associated proteins, GAP-43 and T alpha 1 alpha-tubulin, in lumbar dorsal root ganglia of control and streptozocin-induced diabetic rats. After 8 weeks of diabetes...

journal_title：Diabetes

authors： Mohiuddin L,Fernyhough P,Tomlinson DR

更新日期：1995-01-01 00:00:00

abstract：:New cellular-based reagents are needed to diagnose type I diabetes as well as to monitor the outcomes of clinical trials at early time points. Four new monoclonal antibodies (mAbs) have been shown to demonstrate reduced binding to lymphocytes from identical twins with long-term type I diabetes relative to that observe...

journal_title：Diabetes

authors： Pinies JA,Fu Y,Vazquez JA,Faustman D

更新日期：1997-03-01 00:00:00

abstract：:Susceptibility of mice to experimental insulin-dependent diabetes as induced by multiple subdiabetogenic doses of streptozotocin has been shown to be strongly gender-dependent, males being much more susceptible than females. We examined this gender difference further in two strains of genetically susceptible mice to d...

journal_title：Diabetes

authors： Paik SG,Michelis MA,Kim YT,Shin S

更新日期：1982-08-01 00:00:00

abstract：:Monoclonal antibodies to T-cell coreceptors have been shown to tolerise autoreactive T-cells and prevent or even reverse autoimmune pathology. In type 1 diabetes, there is a loss of insulin-secreting beta-cells, and a cure for type 1 diabetes would require not only tolerance induction but also recovery of the function...

journal_title：Diabetes

authors： Phillips JM,O'Reilly L,Bland C,Foulis AK,Cooke A

更新日期：2007-03-01 00:00:00

abstract：:Interleukin-6 (IL-6) is a pleiotropic cytokine involved in the pathophysiology of various human diseases such as type 2 diabetes and obesity. IL-6 signals via a heterodimeric receptor complex consisting of a soluble IL-6 alpha-subunit (IL-6 receptor [IL6R]) and a signal transducing subunit (gp130). The IL6R gene maps ...

journal_title：Diabetes

authors： Hamid YH,Urhammer SA,Jensen DP,Glümer C,Borch-Johnsen K,Jørgensen T,Hansen T,Pedersen O

更新日期：2004-12-01 00:00:00

abstract：OBJECTIVE:Evidence links the hypothalamic fatty acid synthase (FAS) pathway to the regulation of food intake and body weight. This includes pharmacological inhibitors that potently reduce feeding and body weight. The mammalian target of rapamycin (mTOR) is an intracellular fuel sensor whose activity in the hypothalamus...

journal_title：Diabetes

authors： Proulx K,Cota D,Woods SC,Seeley RJ

更新日期：2008-12-01 00:00:00

abstract：OBJECTIVE:Epidemiological and family studies have demonstrated that susceptibility genes play an important role in the etiology of diabetic nephropathy, defined as persistent proteinuria or end-stage renal disease (ESRD) in type 1 diabetes. RESEARCH DESIGN AND METHODS:To efficiently search for genomic regions harborin...

journal_title：Diabetes

authors： Rogus JJ,Poznik GD,Pezzolesi MG,Smiles AM,Dunn J,Walker W,Wanic K,Moczulski D,Canani L,Araki S,Makita Y,Warram JH,Krolewski AS

更新日期：2008-09-01 00:00:00

abstract：:Islet amyloid polypeptide (IAPP) or amylin is a newly identified 37-amino acid COOH-terminal-amidated polypeptide that is the major protein constituent of amyloid deposits in insulinomas and amyloid deposits in pancreatic islets of non-insulin-dependent (type II) diabetic humans and adult diabetic cats. IAPP is stored...

journal_title：Diabetes

authors： Johnson KH,O'Brien TD,Westermark P

更新日期：1991-03-01 00:00:00

abstract：:The type I and type II isozymes of hexokinase coexist in insulin-sensitive tissues, such as cardiac and skeletal muscle and adipose tissue. Based on an early report that the purified type I isozyme was stable at 45 degrees C whereas the purified type II isozyme was not, investigators in a number of studies have used h...

journal_title：Diabetes

authors： Wilson JE

更新日期：1998-10-01 00:00:00

abstract：:The cell death-inducing DFFA (DNA fragmentation factor-alpha)-like effector A (CIDEA) gene is implicated as an important regulator of body weight in mice and humans and is therefore a candidate gene for human obesity. Here, we characterize common CIDEA gene polymorphisms and investigate them for association with obesi...

journal_title：Diabetes

authors： Dahlman I,Kaaman M,Jiao H,Kere J,Laakso M,Arner P

更新日期：2005-10-01 00:00:00

abstract：:Impaired skeletal muscle fatty acid oxidation has been suggested to contribute to insulin resistance and glucose intolerance. However, increasing muscle fatty acid oxidation may cause a reciprocal decrease in glucose oxidation, which might impair insulin sensitivity and glucose tolerance. We therefore investigated wha...

journal_title：Diabetes

authors： Keung W,Ussher JR,Jaswal JS,Raubenheimer M,Lam VH,Wagg CS,Lopaschuk GD

更新日期：2013-03-01 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

authors： Jun HS,Santamaria P,Lim HW,Zhang ML,Yoon JW

更新日期：1999-01-01 00:00:00

abstract：:Beiging of white adipose tissue has potential antiobesity and antidiabetes effects, yet the underlying signaling mechanisms remain to be fully elucidated. Here we show that adipose-specific knockout of Rheb, an upstream activator of mechanistic target of rapamycin complex 1 (mTORC1), protects mice from high-fat diet-i...

journal_title：Diabetes

authors： Meng W,Liang X,Chen H,Luo H,Bai J,Li G,Zhang Q,Xiao T,He S,Zhang Y,Xu Z,Xiao B,Liu M,Hu F,Liu F

更新日期：2017-05-01 00:00:00

abstract：:The clearing of monoclonal and polyclonal and anti-insulin antibodies from homogeneous solutions at 100,000 X g was used to estimate the size of soluble insulin-antibody complexes at physiologic concentrations. Monoclonal antibodies cleared as a uniform population of 6.6 S independent of the insulin concentration. Pol...

journal_title：Diabetes

authors： Petersen KG,Storch MJ,Rother K,Licht T,Kerp L

更新日期：1985-08-01 00:00:00

abstract：:There has been great interest in the browning of fat for the treatment of obesity. Although β-lapachone (BLC) has potential therapeutic effects on obesity, the fat-browning effect and thermogenic capacity of BLC on obesity have never been demonstrated. Here, we showed that BLC stimulated the browning of white adipose ...

journal_title：Diabetes

authors： Choi WH,Ahn J,Jung CH,Jang YJ,Ha TY

更新日期：2016-09-01 00:00:00

abstract：:Insulin receptors from rat hepatoma cells (Fao) and human placenta were partially purified by detergent solubilization and lectin purification. The insulin receptor preparations were subjected to sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis under reducing or nonreducing conditions. The proteins were...

journal_title：Diabetes

authors： Maron R,Kahn CR,Jacobs S,Fujita-Yamaguchi Y

更新日期：1984-10-01 00:00:00

abstract：:The beta-3 adrenergic receptor (ADRB3) has been implicated as a regulator of energy expenditure, and a polymorphism in codon 64 of this gene (Trp64Arg) has been associated in some studies with obesity and insulin resistance. However, many studies have failed to detect an effect of this variant, and the importance of t...

journal_title：Diabetes

authors： Mitchell BD,Cole SA,Comuzzie AG,Almasy L,Blangero J,MacCluer JW,Hixson JE

更新日期：1999-09-01 00:00:00

abstract：:Association studies are a potentially powerful approach to identifying susceptibility variants for common multifactorial diseases such as type 1 diabetes, but the results are not always consistently reproducible. The IDDM5 locus has recently been narrowed to an approximately 200-kb interval on chromosome 6q25 by two i...

journal_title：Diabetes

authors： Noso S,Ikegami H,Fujisawa T,Kawabata Y,Asano K,Hiromine Y,Tsurumaru M,Sugihara S,Lee I,Kawasaki E,Awata T,Ogihara T

更新日期：2005-12-01 00:00:00

abstract：:Expansion of pancreatic β-cells is a key goal of diabetes research, yet induction of adult human β-cell replication has proven frustratingly difficult. In part, this reflects a lack of understanding of cell cycle control in the human β-cell. Here, we provide a comprehensive immunocytochemical "atlas" of G1/S control m...

journal_title：Diabetes

authors： Fiaschi-Taesch NM,Kleinberger JW,Salim FG,Troxell R,Wills R,Tanwir M,Casinelli G,Cox AE,Takane KK,Scott DK,Stewart AF

更新日期：2013-07-01 00:00:00

abstract：OBJECTIVE:To evaluate whether healthy or diabetic adult mice can tolerate an extreme loss of pancreatic α-cells and how this sudden massive depletion affects β-cell function and blood glucose homeostasis. RESEARCH DESIGN AND METHODS:We generated a new transgenic model allowing near-total α-cell removal specifically in...

journal_title：Diabetes

authors： Thorel F,Damond N,Chera S,Wiederkehr A,Thorens B,Meda P,Wollheim CB,Herrera PL

更新日期：2011-11-01 00:00:00

abstract：:Hexokinase (HK) II plays an important role in intracellular glucose metabolism by catalyzing the conversion of glucose to glucose-6-phosphate. HKII is considered to be a promising candidate gene for non-insulin-dependent diabetes mellitus (NIDDM) and insulin resistance. Therefore, we investigated the frequency of vari...

journal_title：Diabetes

authors： Laakso M,Malkki M,Deeb SS

更新日期：1995-03-01 00:00:00

abstract：:The molecular underpinnings of β-cell dysfunction and death leading to diabetes are not fully elucidated. The objective of the current study was to investigate the role of endoplasmic reticulum-associated degradation (ERAD) in pancreatic β-cells. Chemically induced ERAD deficiency in the rat insulinoma cell line INS-1...

journal_title：Diabetes

authors： Hu Y,Gao Y,Zhang M,Deng KY,Singh R,Tian Q,Gong Y,Pan Z,Liu Q,Boisclair YR,Long Q

更新日期：2019-04-01 00:00:00

abstract：OBJECTIVE:Macrophages play an important role in the pathogenesis of insulin resistance via the production of proinflammatory cytokines. Our goal is to decipher the molecular linkage between proinflammatory cytokine production and insulin resistance in macrophages. RESEARCH DESIGN AND METHODS:We determined cytokine pro...

journal_title：Diabetes

authors： Su D,Coudriet GM,Hyun Kim D,Lu Y,Perdomo G,Qu S,Slusher S,Tse HM,Piganelli J,Giannoukakis N,Zhang J,Dong HH

更新日期：2009-11-01 00:00:00

abstract：:Insulin signaling in vascular endothelial cells (ECs) is critical to maintain endothelial function but also to mediate insulin action on peripheral glucose disposal. However, gene knockout studies have reached disparate conclusions. Thus, insulin receptor inactivation in ECs does not impair insulin action, whereas ina...

journal_title：Diabetes

authors： Tsuchiya K,Accili D

更新日期：2013-05-01 00:00:00

abstract：:Members of the tumor necrosis factor receptor superfamily play an important role in the initiation, expansion, and termination of an immune response. It has recently been demonstrated that one member of this family, CD30, plays a central role in maintaining peripheral tolerance by controlling the expansion of autoreac...

journal_title：Diabetes

authors： Siegmund T,Armitage N,Wicker LS,Peterson LB,Todd JA,Lyons PA

更新日期：2000-09-01 00:00:00

abstract：:IA-2 and IA-2beta are members of the transmembrane protein tyrosine phosphatase family located in dense core vesicles of neuroendocrine cells, including the beta-cells of pancreatic islets. In the present study, by mating C57BL/6Nci IA-2(+/-) with IA-2beta(+/-) mice, we generated double knockout mice (IA-2(-/-)/IA-2be...

journal_title：Diabetes

authors： Kubosaki A,Nakamura S,Notkins AL

更新日期：2005-12-01 00:00:00

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 re...

journal_title：Diabetes

authors： Huynh FK,Levi J,Denroche HC,Gray SL,Voshol PJ,Neumann UH,Speck M,Chua SC,Covey SD,Kieffer TJ

更新日期：2010-12-01 00:00:00

abstract：:Glucose controls islet beta-cell mass and function at least in part through the phosphatidylinositol 3-kinase (PI3K)/Akt pathway downstream of insulin signaling. The Foxo proteins, transcription factors known in other tissues to be negatively regulated by Akt activation, affect proliferation and metabolism. In this st...

journal_title：Diabetes

authors： Martinez SC,Cras-Méneur C,Bernal-Mizrachi E,Permutt MA

更新日期：2006-06-01 00:00:00

abstract：:This genome-wide search for susceptibility genes to type 2 diabetes/impaired glucose homeostasis (IGH) was performed on a relatively homogeneous Chinese sample with a total number of 257 pedigrees and 385 affected sibpairs. Two regions showed significant linkage to type 2 diabetes/IGH in the Chinese. The region showin...

journal_title：Diabetes

authors： Xiang K,Wang Y,Zheng T,Jia W,Li J,Chen L,Shen K,Wu S,Lin X,Zhang G,Wang C,Wang S,Lu H,Fang Q,Shi Y,Zhang R,Xu J,Weng Q

更新日期：2004-01-01 00:00:00

abstract：:The uptake of 2-deoxy-D-[1-14C]-glucose, in the presence and absence of insulin, was measured in adipocytes from normal and streptozotocin-diabetic animals, over a wide temperature range (25-45 degrees C). Optimum temperatures for uptake in the presence of maximally stimulating insulin concentrations occurred near phy...

journal_title：Diabetes

authors： Sauerheber RD,Kuhn CE,Hyslop PA

更新日期：1984-03-01 00:00:00