Mining the Genome for Therapeutic Targets.

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

authors： Bhathena SJ,Timmers KI,Oie HK,Voyles NR,Recant L

更新日期：1985-02-01 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

authors： Carr DB,Utzschneider KM,Boyko EJ,Asberry PJ,Hull RL,Kodama K,Callahan HS,Matthys CC,Leonetti DL,Schwartz RS,Kahn SE,Fujimoto WY

更新日期：2005-02-01 00:00:00

abstract：:Type 1 diabetes is perceived as a chronic immune-mediated disease with a subclinical prodromal period characterized by selective loss of insulin-producing beta-cells in the pancreatic islets in genetically susceptible subjects. A series of evidence supports a critical role of exogenous factors in the development of ty...

journal_title：Diabetes

authors： Knip M,Veijola R,Virtanen SM,Hyöty H,Vaarala O,Akerblom HK

更新日期：2005-12-01 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

authors： Giachetti A

更新日期：1978-10-01 00:00:00

abstract：:The appearance of type 1 diabetes (T1D)-associated autoantibodies is the first and only measurable parameter to predict progression toward T1D in genetically susceptible individuals. However, autoantibodies indicate an active autoimmune reaction, wherein the immune tolerance is already broken. Therefore, there is a cl...

journal_title：Diabetes

authors： Kallionpää H,Somani J,Tuomela S,Ullah U,de Albuquerque R,Lönnberg T,Komsi E,Siljander H,Honkanen J,Härkönen T,Peet A,Tillmann V,Chandra V,Anagandula MK,Frisk G,Otonkoski T,Rasool O,Lund R,Lähdesmäki H,Knip M,Lahes

更新日期：2019-10-01 00:00:00

abstract：:Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone with extrapancreatic effects beyond glycemic control. Here we demonstrate unexpected effects of GIP signaling in the vasculature. GIP induces the expression of the proatherogenic cytokine osteopontin (OPN) in mouse arteries via local release of ...

journal_title：Diabetes

authors： Berglund LM,Lyssenko V,Ladenvall C,Kotova O,Edsfeldt A,Pilgaard K,Alkayyali S,Brøns C,Forsblom C,Jonsson A,Zetterqvist AV,Nitulescu M,McDavitt CR,Dunér P,Stancáková A,Kuusisto J,Ahlqvist E,Lajer M,Tarnow L,Madsbad S

更新日期：2016-01-01 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

authors： Beattie G,Lannom R,Lipsick J,Kaplan NO,Osler AG

更新日期：1980-02-01 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

authors： Graves PM,Norris JM,Pallansch MA,Gerling IC,Rewers M

更新日期：1997-02-01 00:00:00

abstract：:Direct methods for measuring the secretion rate of insulin are too cumbersome for clinical application. Since C-peptide is secreted in an equimolar ratio with insulin and is excreted into the urine, measuring the urinary excretion rate of C-peptide (U-C) could serve as an indicator of its secretion rate (SR-C) if its ...

journal_title：Diabetes

authors： Meistas MT,Rendell M,Margolis S,Kowarski AA

更新日期：1982-05-01 00:00:00

abstract：:A workshop sponsored by the National Institute of Child Health and Human Development was held in June 1988 to discuss the initial events in the pathogenesis of insulin-dependent diabetes and to make recommendations for future studies. Better definition of immunological markers to reliably predict the disease will enab...

journal_title：Diabetes

authors： Maclaren N,Schatz D,Drash A,Grave G

更新日期：1989-04-01 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：:Glucose stimulates insulin secretion by generating triggering and amplifying signals in beta-cells. The triggering pathway is well characterized. It involves the following sequence of events: entry of glucose by facilitated diffusion, metabolism of glucose by oxidative glycolysis, rise in the ATP-to-ADP ratio, closure...

journal_title：Diabetes

authors： Henquin JC

更新日期：2000-11-01 00:00:00

abstract：:Increased pancreas mass and glucagon-positive adenomas have been suggested to be a risk associated with sitagliptin or exenatide therapy in humans. Novo Nordisk has conducted extensive toxicology studies, including data on pancreas weight and histology, in Cynomolgus monkeys dosed with two different human glucagon-lik...

journal_title：Diabetes

authors： Gotfredsen CF,Mølck AM,Thorup I,Nyborg NC,Salanti Z,Knudsen LB,Larsen MO

更新日期：2014-07-01 00:00:00

abstract：:Obesity is a common problem in Western society and is associated with significant morbidity and mortality. Energy homeostasis is regulated by a complex system involving both peripheral signals such as leptin and a number of orexigenic and anorectic neuropeptides. Obesity can result from dysregulation of the peripheral...

journal_title：Diabetes

authors： Bradley RL,Kokkotou EG,Maratos-Flier E,Cheatham B

更新日期：2000-07-01 00:00:00

abstract：:The effect of 4 wk of streptozocin (STZ)-induced diabetes on the transmission time of the auditory-evoked brain stem response (ABR) was examined in conscious male Sprague-Dawley rats. Distal nerve transmission time of the auditory pathway (latency of peak II), which includes conduction along the 8th cranial nerve, inc...

journal_title：Diabetes

authors： Notvest RR,Inserra JJ

更新日期：1987-04-01 00:00:00

abstract：:To characterize the differentiation events that selectively target insulin-producing cells to interleukin (IL)-1beta-induced apoptosis, we studied IL-1beta signaling via mitogen-activated protein kinase (MAPK) and stress-activated protein kinase in 2 pancreatic endocrine cell lines. We studied the glucagon-secreting A...

journal_title：Diabetes

authors： Ammendrup A,Maillard A,Nielsen K,Aabenhus Andersen N,Serup P,Dragsbaek Madsen O,Mandrup-Poulsen T,Bonny C

更新日期：2000-09-01 00:00:00

abstract：OBJECTIVE:Leptin released from adipocytes plays a key role in the control of food intake, energy balance, and glucose homeostasis. In addition to its central action, leptin directly affects pancreatic beta-cells, inhibiting insulin secretion, and, thus, modulating glucose homeostasis. However, despite the importance of...

journal_title：Diabetes

authors： Tudurí E,Marroquí L,Soriano S,Ropero AB,Batista TM,Piquer S,López-Boado MA,Carneiro EM,Gomis R,Nadal A,Quesada I

更新日期：2009-07-01 00:00:00

abstract：:Signaling pathways activated by leptin in metabolically important organs have largely been studied only in animal and/or cell culture studies. In this study, we examined whether leptin has similar effects in human peripheral tissues in vivo, ex vivo, and in vitro and whether the response would be different in lean and...

journal_title：Diabetes

authors： Moon HS,Huh JY,Dincer F,Schneider BE,Hasselgren PO,Mantzoros CS

更新日期：2015-03-01 00:00:00

abstract：:This study assessed the site of increased glucose uptake resulting from insulin inhalation, quantified its effect under steady-state glucose concentrations, and identified the time to onset of effect. Human insulin was administered to 13 beagles via inhalation (Exubera [insulin human (rDNA origin)] Inhalation Powder; ...

journal_title：Diabetes

authors： Edgerton DS,Cherrington AD,Williams P,Neal DW,Scott M,Bowen L,Wilson W,Hobbs CH,Leach C,Kuo MC,Strack TR

更新日期：2006-12-01 00:00:00

abstract：:Specific binding of [3H]SCH 23390 to dopamine D1 receptors in the striatum and olfactory tubercle in 14-day alloxan-induced diabetic rats was investigated. The Scatchard analysis revealed decreased D1 receptor density in the striatum (Bmax values were 548 +/- 23 fmol/mg protein for the control and 466 +/- 33 fmol/mg f...

journal_title：Diabetes

authors： Salković M,Lacković Z

更新日期：1992-09-01 00:00:00

abstract：:The aim of this study was to investigate whether mutations in hepatocyte nuclear factor (HNF)-4gamma, a transcription factor homologous to HNF-4alpha, contribute to the etiology of early-onset type 2 diabetes. Linkage between diabetes and two polymorphic markers at the HNF-4gamma locus (D8S286 and D8S548) was evaluate...

journal_title：Diabetes

authors： Plengvidhya N,Antonellis A,Wogan LT,Poleev A,Borgschulze M,Warram JH,Ryffel GU,Krolewski AS,Doria A

更新日期：1999-10-01 00:00:00

abstract：OBJECTIVE:Obesity causes insulin resistance, which has been interpreted as reduced downstream insulin signaling. However, changes in access of insulin to sensitive tissues such as skeletal muscle may also play a role. Insulin injected directly into skeletal muscle diffuses rapidly through the interstitial space to caus...

journal_title：Diabetes

authors： Kolka CM,Harrison LN,Lottati M,Chiu JD,Kirkman EL,Bergman RN

更新日期：2010-03-01 00:00:00

abstract：:Studies have shown associations between exposure to hypoglycemia and increased mortality, raising the possibility that hypoglycemia has adverse cardiovascular effects. In this study, we determined the acute effects of hypoglycemia on cardiovascular autonomic control. Seventeen healthy volunteers were exposed to experi...

journal_title：Diabetes

authors： Rao AD,Bonyhay I,Dankwa J,Baimas-George M,Kneen L,Ballatori S,Freeman R,Adler GK

更新日期：2016-01-01 00:00:00

abstract：:Endothelial cells in culture retain many of the functional properties of the endothelium in vivo. At high cell density, they become contact-inhibited. Endothelial cells, like vascular smooth muscle cells and fibroblasts, express binding sites for low density lipoprotein when depleted of sterol. In contact-inhibited en...

journal_title：Diabetes

authors： Fielding CJ

更新日期：1981-01-01 00:00:00

abstract：OBJECTIVE:A number of studies have found that reduced birth weight is associated with type 2 diabetes later in life; however, the underlying mechanism for this correlation remains unresolved. Recently, association has been demonstrated between low birth weight and single nucleotide polymorphisms (SNPs) at the CDKAL1 an...

journal_title：Diabetes

authors： Zhao J,Li M,Bradfield JP,Wang K,Zhang H,Sleiman P,Kim CE,Annaiah K,Glaberson W,Glessner JT,Otieno FG,Thomas KA,Garris M,Hou C,Frackelton EC,Chiavacci RM,Berkowitz RI,Hakonarson H,Grant SF

更新日期：2009-10-01 00:00:00

abstract：:Recent evidence highlights the therapeutic potential of peroxisome proliferator-activated receptor-δ (PPARδ) agonists to increase insulin sensitivity in diabetes. However, the role of PPARδ in regulating vascular function is incompletely characterized. We investigate whether PPARδ activation improves endothelial funct...

journal_title：Diabetes

authors： Tian XY,Wong WT,Wang N,Lu Y,Cheang WS,Liu J,Liu L,Liu Y,Lee SS,Chen ZY,Cooke JP,Yao X,Huang Y

更新日期：2012-12-01 00:00:00

abstract：:The effect of insulin on glycogen synthase activity in human diploid fibroblasts has been studied. As little as 2 X 10(-10) M insulin increased the glycogen synthase / activity without changing the total activity. Stimulation occurred within 5 min and became maximal in 30 min. A half-maximal increase of / activity was...

journal_title：Diabetes

authors： Hidaka H,Howard BV,Kosmakos FC,Fields RM,Craig JW,Bennett PH,Larner J

更新日期：1980-10-01 00:00:00

abstract：:One month following induction of diabetes with streptozotocin, one half of diabetic and control rats underwent unilateral nephrectomy. Subsequently, all animals were studied with respect to renal function and glomerular alterations of diabetes. Blood pressure levels were similar in all animals. Diabetic and control an...

journal_title：Diabetes

authors： Steffes MW,Brown DM,Mauer SM

更新日期：1978-01-01 00:00:00

abstract：:In skeletal muscle, the actin cytoskeleton-regulating GTPase, Rac1, is necessary for insulin-dependent GLUT4 translocation. Muscle contraction increases glucose transport and represents an alternative signaling pathway to insulin. Whether Rac1 is activated by muscle contraction and regulates contraction-induced glucos...

journal_title：Diabetes

authors： Sylow L,Jensen TE,Kleinert M,Mouatt JR,Maarbjerg SJ,Jeppesen J,Prats C,Chiu TT,Boguslavsky S,Klip A,Schjerling P,Richter EA

更新日期：2013-04-01 00:00:00

abstract：OBJECTIVE:Normal human myocardium switches substrate metabolism preference, adapting to the prevailing plasma substrate levels and hormonal milieu, but in type 1 diabetes, the myocardium relies heavily on fatty acid metabolism for energy. Whether conditions that affect myocardial glucose use and fatty acid utilization,...

journal_title：Diabetes

authors： Peterson LR,Herrero P,McGill J,Schechtman KB,Kisrieva-Ware Z,Lesniak D,Gropler RJ

更新日期：2008-01-01 00:00:00