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4361. Insulin mutation screening in 1,044 patients with diabetes: mutations in the INS gene are a common cause of neonatal diabetes but a rare cause of diabetes diagnosed in childhood or adulthood.
作者: Emma L Edghill.;Sarah E Flanagan.;Ann-Marie Patch.;Chris Boustred.;Andrew Parrish.;Beverley Shields.;Maggie H Shepherd.;Khalid Hussain.;Ritika R Kapoor.;Maciej Malecki.;Michael J MacDonald.;Julie Støy.;Donald F Steiner.;Louis H Philipson.;Graeme I Bell.; .;Andrew T Hattersley.;Sian Ellard.
来源: Diabetes. 2008年57卷4期1034-42页
Insulin gene (INS) mutations have recently been described as a cause of permanent neonatal diabetes (PND). We aimed to determine the prevalence, genetics, and clinical phenotype of INS mutations in large cohorts of patients with neonatal diabetes and permanent diabetes diagnosed in infancy, childhood, or adulthood.
4362. Evidence of interaction between PPARG2 and HNF4A contributing to variation in insulin sensitivity in Mexican Americans.
作者: Mary Helen Black.;Tasha E Fingerlin.;Hooman Allayee.;Weiming Zhang.;Anny H Xiang.;Enrique Trigo.;Jaana Hartiala.;Allison B Lehtinen.;Steven M Haffner.;Richard N Bergman.;Richard C McEachin.;Siri L Kjos.;Jean M Lawrence.;Thomas A Buchanan.;Richard M Watanabe.
来源: Diabetes. 2008年57卷4期1048-56页
We hypothesized that interaction between PPARG2 Pro12Ala and variants in the promoter region of HNF4A are associated with type 2 diabetes-related quantitative traits in Mexican-American families of a proband with previous gestational diabetes.
4363. PPARGC1A variation associated with DNA damage, diabetes, and cardiovascular diseases: the Boston Puerto Rican Health Study.
作者: Chao-Qiang Lai.;Katherine L Tucker.;Laurence D Parnell.;Xian Adiconis.;Bibiana García-Bailo.;John Griffith.;Mohsen Meydani.;José M Ordovás.
来源: Diabetes. 2008年57卷4期809-16页
Individuals with type 2 diabetes exhibit higher DNA damage and increased risk of cardiovascular disease (CVD). However, mechanisms underlying the association between DNA damage and development of type 2 diabetes and CVD are not understood. We sought to link peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PPARGC1A), a master transcriptional regulator of mitochondrial oxidative phosphorylation and cellular energy metabolism, with DNA damage, type 2 diabetes, and CVD.
4364. Reversal of streptozotocin-induced diabetes in mice by cellular transduction with recombinant pancreatic transcription factor pancreatic duodenal homeobox-1: a novel protein transduction domain-based therapy.
作者: Vijay Koya.;Shun Lu.;Yu-Ping Sun.;Daniel L Purich.;Mark A Atkinson.;Shi-Wu Li.;Li-Jun Yang.
来源: Diabetes. 2008年57卷3期757-69页
The key pancreatic transcription factor pancreatic duodenal homeobox-1 (Pdx1), known to control development and maintenance of pancreatic beta-cells, possesses a protein transduction domain (PTD) that facilitates its entry into cells. We therefore sought to evaluate the capacity of in vivo-administered recombinant Pdx1 (rPdx1) to ameliorate hyperglycemia in mice with streptozotocin-induced diabetes.
4365. Increased skeletal muscle tumor necrosis factor-alpha and impaired insulin signaling persist in obese women with gestational diabetes mellitus 1 year postpartum.
作者: Jacob E Friedman.;John P Kirwan.;Ming Jing.;Larraine Presley.;Patrick M Catalano.
来源: Diabetes. 2008年57卷3期606-13页
Women with gestational diabetes mellitus (GDM) demonstrate chronic and progressive insulin resistance and a markedly increased risk of converting to type 2 diabetes after pregnancy. However, the cellular mechanisms underlying this insulin resistance are unknown.
4366. Thrombospondin-1 is an adipokine associated with obesity, adipose inflammation, and insulin resistance.
作者: Vijayalakshmi Varma.;Aiwei Yao-Borengasser.;Angela M Bodles.;Neda Rasouli.;Bounleut Phanavanh.;Greg T Nolen.;Emily M Kern.;Radhakrishnan Nagarajan.;Horace J Spencer.;Mi-Jeong Lee.;Susan K Fried.;Robert E McGehee.;Charlotte A Peterson.;Philip A Kern.
来源: Diabetes. 2008年57卷2期432-9页
We examined the relationship between the expression of thrombospondin (TSP)1, an antiangiogenic factor and regulator of transforming growth factor-beta activity, obesity, adipose inflammation, and insulin resistance.
4367. Nephropathy in type 1 diabetes is diminished in carriers of HLA-DRB1*04: the genetics of kidneys in diabetes (GoKinD) study.
作者: Suzanne K Cordovado.;Yuan Zhao.;James H Warram.;Hongguang Gong.;Karen L Anderson.;Miyono M Hendrix.;Laura N Hancock.;Patricia A Cleary.;Patricia W Mueller.
来源: Diabetes. 2008年57卷2期518-22页
The purpose of this study was to examine whether known genetic risk factors for type 1 diabetes (HLA-DRB1, -DQA1, and -DQB1 and insulin locus) play a role in the etiology of diabetic nephropathy. RESEARCH DESIGN AND METHODS; Genetic analysis of HLA-DRB1, -DQA1, -DQB1 and the insulin gene (INS) was performed in the Genetics of Kidneys in Diabetes (GoKinD) collection of DNA (European ancestry subset), which includes case patients with type 1 diabetes and nephropathy (n = 829) and control patients with type 1 diabetes but not nephropathy (n = 904). The availability of phenotypic and genotypic data on GoKinD participants allowed a detailed analysis of the association of these genes with diabetic nephropathy.
4368. Inhibition of AMP-activated protein kinase protects pancreatic beta-cells from cytokine-mediated apoptosis and CD8+ T-cell-induced cytotoxicity.
作者: Audrey Riboulet-Chavey.;Frédérique Diraison.;L Khai Siew.;F Susan Wong.;Guy A Rutter.
来源: Diabetes. 2008年57卷2期415-23页
Apoptotic destruction of insulin-producing pancreatic beta-cells is involved in the etiology of both type 1 and type 2 diabetes. AMP-activated protein kinase (AMPK) is a sensor of cellular energy charge whose sustained activation has recently been implicated in pancreatic beta-cell apoptosis and in islet cell death posttransplantation. Here, we examine the importance of beta-cell AMPK in cytokine-induced apoptosis and in the cytotoxic action of CD8(+) T-cells.
4369. Proinflammatory effects of advanced lipoxidation end products in monocytes.
作者: Narkunarajaa Shanmugam.;James L Figarola.;Yan Li.;Piotr M Swiderski.;Samual Rahbar.;Rama Natarajan.
来源: Diabetes. 2008年57卷4期879-88页
The reactions of carbohydrate- or lipid-derived intermediates with proteins lead to the formation of Maillard reaction products, which subsequently leads to the formation of advanced glycation/lipoxidation end products (AGE/ALEs). Levels of AGE/ALEs are increased in diseases like diabetes. Unlike AGEs, very little is known about ALE effects in vitro. We hypothesized that ALEs can have proinflammatory effects in monocytes.
4370. Attenuation of counterregulatory responses to recurrent hypoglycemia by active thalamic inhibition: a mechanism for hypoglycemia-associated autonomic failure.
作者: Ana Maria Arbelaez.;William J Powers.;Tom O Videen.;Joseph L Price.;Philip E Cryer.
来源: Diabetes. 2008年57卷2期470-5页
Hypoglycemia, the limiting factor in the glycemic management of diabetes, is the result of the interplay of therapeutic insulin excess and compromised glycemic defenses. The key feature of the latter is an attenuated sympathoadrenal response to hypoglycemia that typically follows an episode of recent antecedent iatrogenic hypoglycemia, a phenomenon termed hypoglycemia-associated autonomic failure (HAAF) in diabetes. We investigated the role of cerebral mechanisms in HAAF by measuring regional brain activation during recurrent hypoglycemia with attenuated counterregulatory responses and comparing it with initial hypoglycemia in healthy individuals.
4371. Cyclical and alternating infusions of glucose and intralipid in rats inhibit insulin gene expression and Pdx-1 binding in islets.
作者: Derek K Hagman.;Martin G Latour.;Swarup K Chakrabarti.;Ghislaine Fontes.;Julie Amyot.;Caroline Tremblay.;Meriem Semache.;James A Lausier.;Violet Roskens.;Raghavendra G Mirmira.;Thomas L Jetton.;Vincent Poitout.
来源: Diabetes. 2008年57卷2期424-31页
Prolonged exposure of isolated islets of Langerhans to elevated levels of fatty acids, in the presence of high glucose, impairs insulin gene expression via a transcriptional mechanism involving nuclear exclusion of pancreas-duodenum homeobox-1 (Pdx-1) and loss of MafA expression. Whether such a phenomenon also occurs in vivo is unknown. Our objective was therefore to ascertain whether chronic nutrient oversupply inhibits insulin gene expression in vivo.
4372. Nonobese diabetic (NOD) mice congenic for a targeted deletion of 12/15-lipoxygenase are protected from autoimmune diabetes.
作者: Marcia McDuffie.;Nelly A Maybee.;Susanna R Keller.;Brian K Stevens.;James C Garmey.;Margaret A Morris.;Elizabeth Kropf.;Claudia Rival.;Kaiwen Ma.;Jeffrey D Carter.;Sarah A Tersey.;Craig S Nunemaker.;Jerry L Nadler.
来源: Diabetes. 2008年57卷1期199-208页
12/15-lipoxygenase (12/15-LO), one of a family of fatty acid oxidoreductase enzymes, reacts with polyenoic fatty acids to produce proinflammatory lipids. 12/15-LO is expressed in macrophages and pancreatic beta-cells. It enhances interleukin 12 production by macrophages, and several of its products induce apoptosis of beta-cells at nanomolar concentrations in vitro. We had previously demonstrated a role for 12/15-LO in beta-cell damage in the streptozotocin model of diabetes. Since the gene encoding 12/15-LO (gene designation Alox15) lies within the Idd4 diabetes susceptibility interval in NOD mice, we hypothesized that 12/15-LO is also a key regulator of diabetes susceptibility in the NOD mouse.
4373. Inactivation of glyceraldehyde-3-phosphate dehydrogenase by fumarate in diabetes: formation of S-(2-succinyl)cysteine, a novel chemical modification of protein and possible biomarker of mitochondrial stress.
(2-succinyl)cysteine (2SC) is formed by a Michael addition reaction of the Krebs cycle intermediate, fumarate, with cysteine residues in protein. We investigated the role of fumarate in chemical modification and inhibition of the sulfhydryl enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), in vitro and in tissues of diabetic rats.
4374. Defective lipid delivery modulates glucose tolerance and metabolic response to diet in apolipoprotein E-deficient mice.
作者: Susanna M Hofmann.;Diego Perez-Tilve.;Todd M Greer.;Beth A Coburn.;Erin Grant.;Joshua E Basford.;Matthias H Tschöp.;David Y Hui.
来源: Diabetes. 2008年57卷1期5-12页
Apolipoprotein E (ApoE) regulates plasma lipid levels via modulation of lipolysis and serving as ligand for receptor-mediated clearance of triglyceride (TG)-rich lipoproteins. This study tested the impact of modulating lipid delivery to tissues on insulin responsiveness and diet-induced obesity.
4375. Multiple superoxide dismutase 1/splicing factor serine alanine 15 variants are associated with the development and progression of diabetic nephropathy: the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Genetics study.
作者: Hussam Al-Kateb.;Andrew P Boright.;Lucia Mirea.;Xinlei Xie.;Rinku Sutradhar.;Alireza Mowjoodi.;Bhupinder Bharaj.;Michelle Liu.;Jean M Bucksa.;Valerie L Arends.;Michael W Steffes.;Patricia A Cleary.;Wanjie Sun.;John M Lachin.;Paul S Thorner.;Michael Ho.;Amy Jayne McKnight.;A Peter Maxwell.;David A Savage.;Kenneth K Kidd.;Judith R Kidd.;William C Speed.;Trevor J Orchard.;Rachel G Miller.;Lei Sun.;Shelley B Bull.;Andrew D Paterson.; .
来源: Diabetes. 2008年57卷1期218-28页
Despite familial clustering of nephropathy and retinopathy severity in type 1 diabetes, few gene variants have been consistently associated with these outcomes.
4376. A 20-year prospective study of childbearing and incidence of diabetes in young women, controlling for glycemia before conception: the Coronary Artery Risk Development in Young Adults (CARDIA) Study.
作者: Erica P Gunderson.;Cora E Lewis.;Ai-Lin Tsai.;Vicky Chiang.;Mercedes Carnethon.;Charles P Quesenberry.;Stephen Sidney.
来源: Diabetes. 2007年56卷12期2990-6页
We sought to determine whether childbearing increases incidence of type 2 diabetes after accounting for preconception glycemia and gestational glucose intolerance.
4377. Variants in the plasmacytoma variant translocation gene (PVT1) are associated with end-stage renal disease attributed to type 1 diabetes.
作者: Meredith P Millis.;Danielle Bowen.;Christopher Kingsley.;Richard M Watanabe.;Johanna K Wolford.
来源: Diabetes. 2007年56卷12期3027-32页
End-stage renal disease (ESRD) attributed to diabetes is strongly dependent on genetic factors. We previously reported association between variants in the plasmacytoma variant translocation gene (PVT1) and ESRD attributed to type 2 diabetes in Pima Indians. The objective of this study was to evaluate the extent to which these variants mediate susceptibility in other populations.
4378. Aberrant endometrial features of pregnancy in diabetic NOD mice.
Pregnant diabetic women are at a 4-12 times higher risk for preeclampsia, an urgent acute-onset complication of mid- to late gestation, than normal pregnant women. Hallmarks of preeclampsia are hypertension, proteinuria, and incomplete modification of endometrial spiral arteries. Transient proangiogenic lymphocytes called uterine natural killer (uNK) cells are implicated in human and rodent spiral artery modification. We studied mid- to late gestations in spontaneously type 1 diabetic NOD mice to investigate whether diabetes alters uNK cell homing and/or function.
4379. Central insulin regulates heart rate and arterial blood flow: an endothelial nitric oxide synthase-dependent mechanism altered during diabetes.
作者: Cendrine Cabou.;Patrice D Cani.;Gérard Campistron.;Claude Knauf.;Caroline Mathieu.;Claudio Sartori.;Jacques Amar.;Urs Scherrer.;Rémy Burcelin.
来源: Diabetes. 2007年56卷12期2872-7页
Central neural insulin regulates glucose homeostasis, but less is known about its cardiovascular effects. Endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) represents a molecular link between metabolic and cardiovascular disease. Its role in the central nervous system remains to be determined. We studied the effects of central insulin infusion on femoral arterial blood flow and heart rate in normal chow-fed, high-fat diet-fed diabetic, and eNOS-null mice.
4380. Childhood predictors of young-onset type 2 diabetes.
作者: Paul W Franks.;Robert L Hanson.;William C Knowler.;Carol Moffett.;Gleebah Enos.;Aniello M Infante.;Jonathan Krakoff.;Helen C Looker.
来源: Diabetes. 2007年56卷12期2964-72页
Optimal prevention of young-onset type 2 diabetes requires identification of the early-life modifiable risk factors. We aimed to do this using longitudinal data in 1,604 5- to 19-year-old initially nondiabetic American Indians.
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