abstract：:Type 1 diabetes is preceded by islet β-cell dysfunction, but the mechanisms leading to β-cell dysfunction have not been rigorously studied. Because immune cell infiltration occurs prior to overt diabetes, we hypothesized that activation of inflammatory cascades and appearance of endoplasmic reticulum (ER) stress in β-...

journal_title：Diabetes

authors： Tersey SA,Nishiki Y,Templin AT,Cabrera SM,Stull ND,Colvin SC,Evans-Molina C,Rickus JL,Maier B,Mirmira RG

更新日期：2012-04-01 00:00:00

abstract：:Cellular cholesterol homeostasis is important for normal β-cell function. Disruption of cholesterol transport by decreased function of the ATP-binding cassette (ABC) transporter ABCA1 results in impaired insulin secretion. Mice lacking β-cell ABCA1 have increased islet expression of ABCG1, another cholesterol transpor...

journal_title：Diabetes

authors： Kruit JK,Wijesekara N,Westwell-Roper C,Vanmierlo T,de Haan W,Bhattacharjee A,Tang R,Wellington CL,LütJohann D,Johnson JD,Brunham LR,Verchere CB,Hayden MR

更新日期：2012-03-01 00:00:00

abstract：:Ectopic lipids in peripheral tissues have been implicated in attenuating insulin action in vivo. The botanical extract of Artemisia dracunculus L. (PMI 5011) improves insulin action, yet the precise mechanism is not known. We sought to determine whether the mechanism by which PMI 5011 improves insulin signaling is thr...

journal_title：Diabetes

authors： Obanda DN,Hernandez A,Ribnicky D,Yu Y,Zhang XH,Wang ZQ,Cefalu WT

更新日期：2012-03-01 00:00:00

abstract：:Low plasma sex hormone-binding globulin (SHBG) levels are associated with obesity and predict the development of type 2 diabetes. The reason why obese individuals have low circulating SHBG has been attributed to hyperinsulinemia, but no mechanistic evidence has been described. The aim of the current study is to explor...

journal_title：Diabetes

authors： Simó R,Barbosa-Desongles A,Lecube A,Hernandez C,Selva DM

更新日期：2012-02-01 00:00:00

abstract：:Glucose-dependent insulinotropic polypeptide (GIP) has been suggested to have direct effects on nonislet tissues. GIP also reportedly increased glucose uptake and inhibition of lipolysis in adipocytes after inhibition of the intracellular cortisone-cortisol shuttle 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). W...

journal_title：Diabetes

authors： Gögebakan Ö,Andres J,Biedasek K,Mai K,Kühnen P,Krude H,Isken F,Rudovich N,Osterhoff MA,Kintscher U,Nauck M,Pfeiffer AF,Spranger J

更新日期：2012-02-01 00:00:00

abstract：:Diabetic nephropathy (DN) is the major life-threatening complication of diabetes. Abnormal permselectivity of glomerular basement membrane (GBM) plays an important role in DN pathogenesis. Heparanase is the predominant enzyme that degrades heparan sulfate (HS), the main polysaccharide of the GBM. Loss of GBM HS in dia...

journal_title：Diabetes

authors： Gil N,Goldberg R,Neuman T,Garsen M,Zcharia E,Rubinstein AM,van Kuppevelt T,Meirovitz A,Pisano C,Li JP,van der Vlag J,Vlodavsky I,Elkin M

更新日期：2012-01-01 00:00:00

abstract：:Type 1 diabetes presents clinically with overt hyperglycemia resulting from progressive immune-mediated destruction of pancreatic β-cells and associated metabolic dysfunction. Combined genetic and immunological studies now highlight deficiencies in both the interleukin-2 (IL-2) receptor and its downstream signaling pa...

journal_title：Diabetes

authors： Hulme MA,Wasserfall CH,Atkinson MA,Brusko TM

更新日期：2012-01-01 00:00:00

abstract：:Pancreatic β-cell ATP-sensitive K(+) (K(ATP)) channels are composed of Kir6.2 and SUR1 subunits encoded by the KCNJ11 and ABCC8 genes, respectively. Although rare monogenic activating mutations in these genes cause overt neonatal diabetes, the common variants E23K (KCNJ11) and S1369A (ABCC8) form a tightly heritable h...

journal_title：Diabetes

authors： Fatehi M,Raja M,Carter C,Soliman D,Holt A,Light PE

更新日期：2012-01-01 00:00:00

abstract：OBJECTIVE:Recent work has shown that insulin stimulates its own secretion in insulin-sensitive humans, suggesting that insulin resistance in the β-cell could cause β-cell dysfunction. We have tested whether insulin exposure and insulin sensitivity modulate β-cell function in subjects with normal glucose tolerance (NGT)...

journal_title：Diabetes

authors： Mari A,Tura A,Natali A,Anderwald C,Balkau B,Lalic N,Walker M,Ferrannini E,RISC Investigators.

更新日期：2011-12-01 00:00:00

abstract：OBJECTIVE:Rosiglitazone (RSG) is an insulin-sensitizing drug used to treat type 2 diabetes mellitus. The A Diabetes Outcome Progression Trial (ADOPT) shows that women taking RSG experienced more fractures than patients taking other type 2 diabetes drugs. These were not osteoporotic vertebral fractures but, rather, occu...

journal_title：Diabetes

authors： Sardone LD,Renlund R,Willett TL,Fantus IG,Grynpas MD

更新日期：2011-12-01 00:00:00

abstract：OBJECTIVE:In humans, it is unclear if insulin resistance at the monocyte level is associated with atherosclerosis in vivo. Here we have studied first-degree relatives of patients with type 2 diabetes to investigate whether a reduction in components of the insulin signal transduction pathways, such as the insulin recept...

journal_title：Diabetes

authors： Cardellini M,Menghini R,Luzi A,Davato F,Cardolini I,D'Alfonso R,Gentileschi P,Rizza S,Marini MA,Porzio O,Lauro D,Sbraccia P,Lauro R,Federici M

更新日期：2011-12-01 00:00:00

abstract：OBJECTIVE:To examine whether the inflammatory phenotype found in obese and diabetic individuals is preserved in isolated, cultured myocytes and to assess the effectiveness of pharmacological AMP-activated protein kinase (AMPK) activation upon the attenuation of inflammation in these myocytes. RESEARCH DESIGN AND METHO...

journal_title：Diabetes

authors： Green CJ,Pedersen M,Pedersen BK,Scheele C

更新日期：2011-11-01 00:00:00

abstract：OBJECTIVE:Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP), now known as G6PC2, is a major target of autoreactive T cells implicated in the pathogenesis of type 1 diabetes in both mice and humans. This study aimed to determine whether suppression of G6p2 gene expression might therefore prev...

journal_title：Diabetes

authors： Oeser JK,Parekh VV,Wang Y,Jegadeesh NK,Sarkar SA,Wong R,Lee CE,Pound LD,Hutton JC,Van Kaer L,O'Brien RM

更新日期：2011-11-01 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：OBJECTIVE:FUT2 encodes the α(1,2) fucosyltransferase that determines blood group secretor status. Homozygotes (A/A) for the common nonsense mutation rs601338A>G (W143X) are nonsecretors and are unable to express histo-blood group antigens in secretions and on mucosal surfaces. This mutation has been reported to provide...

journal_title：Diabetes

authors： Smyth DJ,Cooper JD,Howson JM,Clarke P,Downes K,Mistry T,Stevens H,Walker NM,Todd JA

更新日期：2011-11-01 00:00:00

abstract：OBJECTIVE:The molecular mechanisms responsible for pancreatic β-cell dysfunction in type 2 diabetes remain unresolved. Increased expression of the helix-loop-helix protein Id1 has been found in islets of diabetic mice and in vitro models of β-cell dysfunction. Here, we investigated the role of Id1 in insulin secretion ...

journal_title：Diabetes

authors： Akerfeldt MC,Laybutt DR

更新日期：2011-10-01 00:00:00

abstract：OBJECTIVE:A major feature of type 1 diabetes is the appearance of islet autoantibodies before diagnosis. However, although the genetics of type 1 diabetes is advanced, the genetics of islet autoantibodies needs further investigation. The primary susceptibility loci in type 1 diabetes, the HLA class I and II genes, are ...

journal_title：Diabetes

authors： Howson JM,Stevens H,Smyth DJ,Walker NM,Chandler KA,Bingley PJ,Todd JA

更新日期：2011-10-01 00:00:00

abstract：OBJECTIVE:Sarco-endoplasmic reticulum Ca(2+)-ATPase 2b (SERCA2b) and SERCA3 pump Ca(2+) in the endoplasmic reticulum (ER) of pancreatic β-cells. We studied their role in the control of the free ER Ca(2+) concentration ([Ca(2+)](ER)) and the role of SERCA3 in the control of insulin secretion and ER stress. RESEARCH DES...

journal_title：Diabetes

authors： Ravier MA,Daro D,Roma LP,Jonas JC,Cheng-Xue R,Schuit FC,Gilon P

更新日期：2011-10-01 00:00:00

abstract：OBJECTIVE:Haptoglobin (Hp) is upregulated in both inflammation and obesity. The low chronic inflammatory state, caused by massive adipose tissue macrophage (ATM) infiltration found in obesity, and low adiponectin have been implicated in the development of insulin resistance and hepatosteatosis. The aim of this work was...

journal_title：Diabetes

authors： Lisi S,Gamucci O,Vottari T,Scabia G,Funicello M,Marchi M,Galli G,Arisi I,Brandi R,D'Onofrio M,Pinchera A,Santini F,Maffei M

更新日期：2011-10-01 00:00:00

abstract：OBJECTIVE:The aim of the current study was to evaluate the long-term effects of leptin on glucose metabolism, diabetes complications, and life span in an insulin-dependent diabetes model, the Akita mouse. RESEARCH DESIGN AND METHODS:We cross-mated Akita mice with leptin-expressing transgenic (LepTg) mice to produce Ak...

journal_title：Diabetes

authors： Naito M,Fujikura J,Ebihara K,Miyanaga F,Yokoi H,Kusakabe T,Yamamoto Y,Son C,Mukoyama M,Hosoda K,Nakao K

更新日期：2011-09-01 00:00:00

abstract：OBJECTIVE:Aging increases the risk of developing impaired glucose tolerance (IGT) and type 2 diabetes. It has been proposed that increased reactive oxygen species (ROS) generation by dysfunctional mitochondria could play a role in the pathogenesis of these metabolic abnormalities. We examined whether aging per se (in s...

journal_title：Diabetes

authors： Ghosh S,Lertwattanarak R,Lefort N,Molina-Carrion M,Joya-Galeana J,Bowen BP,Garduno-Garcia Jde J,Abdul-Ghani M,Richardson A,DeFronzo RA,Mandarino L,Van Remmen H,Musi N

更新日期：2011-08-01 00:00:00

abstract：OBJECTIVE:Preferential upper-body fat gain, a typical male pattern, is associated with a greater cardiometabolic risk. Regional differences in lipolysis and meal fat storage cannot explain sex differences in body fat distribution. We examined the potential role of the novel free fatty acid (FFA) storage pathway in dete...

journal_title：Diabetes

authors： Koutsari C,Ali AH,Mundi MS,Jensen MD

更新日期：2011-08-01 00:00:00

abstract：OBJECTIVE:To understand the relationships between maternal glycemia during pregnancy and prenatal and early postnatal growth by evaluating cord C-peptide and IGF-I as mediating biomarkers in boys and girls separately. RESEARCH DESIGN AND METHODS:We evaluated 342 neonates within the EDEN mother-child cohort study born ...

journal_title：Diabetes

authors： Regnault N,Botton J,Heude B,Forhan A,Hankard R,Foliguet B,Hillier TA,Souberbielle JC,Dargent-Molina P,Charles MA,EDEN Mother-Child Cohort Study Group.

更新日期：2011-08-01 00:00:00

abstract：OBJECTIVE:The gut environment modulates the pathogenesis of type 1 diabetes (T1D), but how it affects autoimmunity toward pancreatic β-cells, a self-tissue located outside the intestine, is still unclear. In the small intestine, lamina propria dendritic cells (LPDCs) induce peripheral differentiation of FoxP3(+) regula...

journal_title：Diabetes

authors： Badami E,Sorini C,Coccia M,Usuelli V,Molteni L,Bolla AM,Scavini M,Mariani A,King C,Bosi E,Falcone M

更新日期：2011-08-01 00:00:00

abstract：OBJECTIVE:Circulating glucose inhibits glucose production in normal rodents and humans, but this glucose effectiveness is disrupted in diabetes due partly to sustained hyperglycemia. We hypothesize that hyperglycemia in diabetes impairs hypothalamic glucose sensing to lower glucose production, and changes of glucose tr...

journal_title：Diabetes

authors： Chari M,Yang CS,Lam CK,Lee K,Mighiu P,Kokorovic A,Cheung GW,Lai TY,Wang PY,Lam TK

更新日期：2011-07-01 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

authors： Zhao Y,Banerjee S,Dey N,LeJeune WS,Sarkar PS,Brobey R,Rosenblatt KP,Tilton RG,Choudhary S

更新日期：2011-07-01 00:00:00

abstract：OBJECTIVE:Regulation of obesity development is an important issue to prevent metabolic syndromes. Gene-disrupted mice of phospholipase Cδ1 (PLCδ1), a key enzyme of phosphoinositide turnover, seemed to show leanness. Here we examined whether and how PLCδ1 is involved in obesity. RESEARCH DESIGN AND METHODS:Weight gain,...

journal_title：Diabetes

authors： Hirata M,Suzuki M,Ishii R,Satow R,Uchida T,Kitazumi T,Sasaki T,Kitamura T,Yamaguchi H,Nakamura Y,Fukami K

更新日期：2011-07-01 00:00:00

abstract：OBJECTIVE:High-fat diet (HFD)-induced adipose tissue inflammation is a critical feature of diet-induced insulin resistance (IR); however, the contribution of interleukin-1 receptor I (IL-1RI)-mediated signals to this phenotype has not been defined. We hypothesized that lack of IL-1RI may ameliorate HFD-induced IR by at...

journal_title：Diabetes

authors： McGillicuddy FC,Harford KA,Reynolds CM,Oliver E,Claessens M,Mills KH,Roche HM

更新日期：2011-06-01 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

authors： Sloan C,Tuinei J,Nemetz K,Frandsen J,Soto J,Wride N,Sempokuya T,Alegria L,Bugger H,Abel ED

更新日期：2011-05-01 00:00:00

abstract：OBJECTIVE:On the basis of the role of activin A in inflammation, atherogenesis, and glucose homeostasis, we investigated whether activin A could be related to glucometabolic abnormalities in patients with acute myocardial infarction (MI). RESEARCH DESIGN AND METHODS:Activin A measurement and oral glucose tolerance tes...

journal_title：Diabetes

authors： Andersen GØ,Ueland T,Knudsen EC,Scholz H,Yndestad A,Sahraoui A,Smith C,Lekva T,Otterdal K,Halvorsen B,Seljeflot I,Aukrust P

更新日期：2011-05-01 00:00:00

abstract：OBJECTIVE:Leukocyte infiltration of adipose is a critical determinant of obesity-related metabolic diseases. Fractalkine (CX3CL1) and its receptor (CX3CR1) comprise a chemokine system involved in leukocyte recruitment and adhesion in atherosclerosis, but its role in adipose inflammation and type 2 diabetes is unknown. ...

journal_title：Diabetes

authors： Shah R,Hinkle CC,Ferguson JF,Mehta NN,Li M,Qu L,Lu Y,Putt ME,Ahima RS,Reilly MP

更新日期：2011-05-01 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

authors： Swafford AD,Howson JM,Davison LJ,Wallace C,Smyth DJ,Schuilenburg H,Maisuria-Armer M,Mistry T,Lenardo MJ,Todd JA

更新日期：2011-03-01 00:00:00

abstract：OBJECTIVE:Bariatric surgery causes durable weight loss. Gut hormones are implicated in obesity pathogenesis, dietary failure, and mediating gastrointestinal bypass (GIBP) surgery weight loss. In mice, we determined the effects of diet-induced obesity (DIO), subsequent dieting, and GIBP surgery on ghrelin, peptide YY (P...

journal_title：Diabetes

authors： Chandarana K,Gelegen C,Karra E,Choudhury AI,Drew ME,Fauveau V,Viollet B,Andreelli F,Withers DJ,Batterham RL

更新日期：2011-03-01 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

authors： Aboulaich N,Chui PC,Asara JM,Flier JS,Maratos-Flier E

更新日期：2011-03-01 00:00:00

abstract：OBJECTIVE:Obesity-associated insulin resistance is characterized by a state of chronic, low-grade inflammation that is associated with the accumulation of M1 proinflammatory macrophages in adipose tissue. Although different evidence explains the mechanisms linking the expansion of adipose tissue and adipose tissue macr...

journal_title：Diabetes

authors： Prieur X,Mok CY,Velagapudi VR,Núñez V,Fuentes L,Montaner D,Ishikawa K,Camacho A,Barbarroja N,O'Rahilly S,Sethi JK,Dopazo J,Orešič M,Ricote M,Vidal-Puig A

更新日期：2011-03-01 00:00:00

abstract：OBJECTIVE:Obesity is associated with increased activation of the c-Jun NH(2)-terminal kinase (JNK) in several metabolic organs, including adipose tissue, liver, and skeletal muscle. In this study, we aimed to define the role of JNK activation in adipose tissue in the development of obesity-related insulin resistance. ...

journal_title：Diabetes

authors： Zhang X,Xu A,Chung SK,Cresser JH,Sweeney G,Wong RL,Lin A,Lam KS

更新日期：2011-02-01 00:00:00

abstract：OBJECTIVE:We tested the hypothesis that adrenergic activation, cholinergic activation, or both, mediate the effect of recent antecedent hypoglycemia to reduce the sympathoadrenal response to subsequent hypoglycemia, the key feature of hypoglycemia-associated autonomic failure in diabetes, in humans. RESEARCH DESIGN AN...

journal_title：Diabetes

authors： Ramanathan R,Cryer PE

更新日期：2011-02-01 00:00:00

abstract：OBJECTIVE:To determine the role of hepatocyte growth factor (HGF)/c-Met on β-cell survival in diabetogenic conditions in vivo and in response to cytokines in vitro. RESEARCH DESIGN AND METHODS:We generated pancreas-specific c-Met-null (PancMet KO) mice and characterized their response to diabetes induced by multiple l...

journal_title：Diabetes

authors： Mellado-Gil J,Rosa TC,Demirci C,Gonzalez-Pertusa JA,Velazquez-Garcia S,Ernst S,Valle S,Vasavada RC,Stewart AF,Alonso LC,Garcia-Ocaña A

更新日期：2011-02-01 00:00:00

abstract：OBJECTIVE:Metformin can decrease adiposity and ameliorate obesity-related comorbid conditions, including abnormalities in glucose homeostasis in adolescents, but there are few data evaluating the efficacy of metformin among younger children. Our objective was to determine whether metformin treatment causes weight loss ...

journal_title：Diabetes

authors： Yanovski JA,Krakoff J,Salaita CG,McDuffie JR,Kozlosky M,Sebring NG,Reynolds JC,Brady SM,Calis KA

更新日期：2011-02-01 00:00:00

abstract：OBJECTIVE:Reactive oxygen species (ROS) is one of most important factors in impaired metabolism secretion coupling in pancreatic β-cells. We recently reported that elevated ROS production and impaired ATP production at high glucose in diabetic Goto-Kakizaki (GK) rat islets are effectively ameliorated by Src inhibition,...

journal_title：Diabetes

authors： Mukai E,Fujimoto S,Sato H,Oneyama C,Kominato R,Sato Y,Sasaki M,Nishi Y,Okada M,Inagaki N

更新日期：2011-01-01 00:00:00