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4461. Selective small-molecule agonists of G protein-coupled receptor 40 promote glucose-dependent insulin secretion and reduce blood glucose in mice.
作者: Carina P Tan.;Yue Feng.;Yun-Ping Zhou.;George J Eiermann.;Aleksandr Petrov.;Changyou Zhou.;Songnian Lin.;Gino Salituro.;Peter Meinke.;Ralph Mosley.;Taro E Akiyama.;Monica Einstein.;Sanjeev Kumar.;Joel P Berger.;Sander G Mills.;Nancy A Thornberry.;Lihu Yang.;Andrew D Howard.
来源: Diabetes. 2008年57卷8期2211-9页
Acute activation of G protein-coupled receptor 40 (GPR40) by free fatty acids (FFAs) or synthetic GPR40 agonists enhances insulin secretion. However, it is still a matter of debate whether activation of GPR40 would be beneficial for the treatment of type 2 diabetes, since chronic exposure to FFAs impairs islet function. We sought to evaluate the specific role of GPR40 in islets and its potential as a therapeutic target using compounds that specifically activate GPR40.
4462. Thymic stromal lymphopoietin and thymic stromal lymphopoietin-conditioned dendritic cells induce regulatory T-cell differentiation and protection of NOD mice against diabetes.
作者: Gilles Besin.;Simon Gaudreau.;Michaël Ménard.;Chantal Guindi.;Gilles Dupuis.;Abdelaziz Amrani.
来源: Diabetes. 2008年57卷8期2107-17页
Autoimmune diabetes in the nonobese diabetic (NOD) mouse model results from a breakdown of T-cell tolerance caused by impaired tolerogenic dendritic cell development and regulatory T-cell (Treg) differentiation. Re-establishment of the Treg pool has been shown to confer T-cell tolerance and protection against diabetes. Here, we have investigated whether murine thymic stromal lymphopoietin (TSLP) re-established tolerogenic function of dendritic cells and induced differentiation and/or expansion of Tregs in NOD mice and protection against diabetes.
4463. Implication of genetic variants near TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, and FTO in type 2 diabetes and obesity in 6,719 Asians.
作者: Maggie C Y Ng.;Kyong Soo Park.;Bermseok Oh.;Claudia H T Tam.;Young Min Cho.;Hyoung Doo Shin.;Vincent K L Lam.;Ronald C W Ma.;Wing Yee So.;Yoon Shin Cho.;Hyung-Lae Kim.;Hong Kyu Lee.;Juliana C N Chan.;Nam H Cho.
来源: Diabetes. 2008年57卷8期2226-33页
Recent genome-wide association studies have identified six novel genes for type 2 diabetes and obesity and confirmed TCF7L2 as the major type 2 diabetes gene to date in Europeans. However, the implications of these genes in Asians are unclear.
4464. PANIC-ATTAC: a mouse model for inducible and reversible beta-cell ablation.
作者: Zhao V Wang.;James Mu.;Todd D Schraw.;Laurent Gautron.;Joel K Elmquist.;Bei B Zhang.;Michael Brownlee.;Philipp E Scherer.
来源: Diabetes. 2008年57卷8期2137-48页
Islet transplantations have been performed clinically, but their practical applications are limited. An extensive effort has been made toward the identification of pancreatic beta-cell stem cells that has yielded many insights to date, yet targeted reconstitution of beta-cell mass remains elusive. Here, we present a mouse model for inducible and reversible ablation of pancreatic beta-cells named the PANIC-ATTAC (pancreatic islet beta-cell apoptosis through targeted activation of caspase 8) mouse.
4465. Relationship of abdominal visceral and subcutaneous adipose tissue with lipoprotein particle number and size in type 2 diabetes.
作者: Susan Sam.;Steven Haffner.;Michael H Davidson.;Ralph B D'Agostino.;Steven Feinstein.;George Kondos.;Alfonso Perez.;Theodore Mazzone.
来源: Diabetes. 2008年57卷8期2022-7页
Insulin resistance and type 2 diabetes are associated with an atherogenic lipoprotein profile. We examined the role of visceral and subcutaneous fat depots, independent of BMI, on the dyslipidemia associated with type 2 diabetes.
4466. Partial resistance to peroxisome proliferator-activated receptor-alpha agonists in ZDF rats is associated with defective hepatic mitochondrial metabolism.
作者: Santhosh Satapati.;Tianteng He.;Takeshi Inagaki.;Matthew Potthoff.;Matthew E Merritt.;Victoria Esser.;David J Mangelsdorf.;Steven A Kliewer.;Jeffrey D Browning.;Shawn C Burgess.
来源: Diabetes. 2008年57卷8期2012-21页
Fluxes through mitochondrial pathways are defective in insulin-resistant skeletal muscle, but it is unclear whether similar mitochondrial defects play a role in the liver during insulin resistance and/or diabetes. The purpose of this study is to determine whether abnormal mitochondrial metabolism plays a role in the dysregulation of both hepatic fat and glucose metabolism during diabetes.
4467. Palmitate impairs and eicosapentaenoate restores insulin secretion through regulation of SREBP-1c in pancreatic islets.
作者: Toyonori Kato.;Hitoshi Shimano.;Takashi Yamamoto.;Mayumi Ishikawa.;Shin Kumadaki.;Takashi Matsuzaka.;Yoshimi Nakagawa.;Naoya Yahagi.;Masanori Nakakuki.;Alyssa H Hasty.;Yoshinori Takeuchi.;Kazuto Kobayashi.;Akimitsu Takahashi.;Shigeru Yatoh.;Hiroaki Suzuki.;Hirohito Sone.;Nobuhiro Yamada.
来源: Diabetes. 2008年57卷9期2382-92页
Chronic exposure to fatty acids causes beta-cell failure, often referred to as lipotoxicity. We investigated its mechanisms, focusing on contribution of SREBP-1c, a key transcription factor for lipogenesis.
4468. The human lipodystrophy gene BSCL2/seipin may be essential for normal adipocyte differentiation.
作者: Victoria A Payne.;Neil Grimsey.;Antoinette Tuthill.;Sam Virtue.;Sarah L Gray.;Edoardo Dalla Nora.;Robert K Semple.;Stephen O'Rahilly.;Justin J Rochford.
来源: Diabetes. 2008年57卷8期2055-60页
Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) is a recessive disorder featuring near complete absence of adipose tissue. Remarkably, although the causative gene, BSCL2, has been known for several years, its molecular function and its role in adipose tissue development have not been elucidated. Therefore, we examined whether BSCL2 is involved in the regulation of adipocyte differentiation and the mechanism whereby pathogenic mutations in BSCL2 cause lipodystrophy.
4469. Obese mice lacking inducible nitric oxide synthase are sensitized to the metabolic actions of peroxisome proliferator-activated receptor-gamma agonism.
作者: Patrice Dallaire.;Kerstin Bellmann.;Mathieu Laplante.;Stéphanie Gélinas.;Carolina Centeno-Baez.;Patrice Penfornis.;Marie-Line Peyot.;Martin G Latour.;Julien Lamontagne.;Maria E Trujillo.;Philipp E Scherer.;Marc Prentki.;Yves Deshaies.;André Marette.
来源: Diabetes. 2008年57卷8期1999-2011页
Synthetic ligands for peroxisome proliferator-activated receptor-gamma (PPAR-gamma) improve insulin sensitivity in obesity, but it is still unclear whether inflammatory signals modulate their metabolic actions. In this study, we tested whether targeted disruption of inducible nitric oxide (NO) synthase (iNOS), a key inflammatory mediator in obesity, modulates the metabolic effects of rosiglitazone in obese mice.
4470. siRNA-mediated reduction of inhibitor of nuclear factor-kappaB kinase prevents tumor necrosis factor-alpha-induced insulin resistance in human skeletal muscle.
作者: Reginald L Austin.;Anna Rune.;Karim Bouzakri.;Juleen R Zierath.;Anna Krook.
来源: Diabetes. 2008年57卷8期2066-73页
Proinflammatory cytokines contribute to systemic low-grade inflammation and insulin resistance. Tumor necrosis factor (TNF)-alpha impedes insulin signaling in insulin target tissues. We determined the role of inhibitor of nuclear factor-kappaB kinase (IKK)beta in TNF-alpha-induced impairments in insulin signaling and glucose metabolism in skeletal muscle.
4471. Exposure to maternal diabetes induces salt-sensitive hypertension and impairs renal function in adult rat offspring.
作者: Touria Nehiri.;Jean-Paul Duong Van Huyen.;Mélanie Viltard.;Céline Fassot.;Didier Heudes.;Nicole Freund.;Georges Deschênes.;Pascal Houillier.;Patrick Bruneval.;Martine Lelièvre-Pégorier.
来源: Diabetes. 2008年57卷8期2167-75页
Epidemiological and experimental studies have led to the hypothesis of fetal origin of adult diseases, suggesting that some adult diseases might be determined before birth by altered fetal development. We have previously demonstrated in the rat that in utero exposure to maternal diabetes impairs renal development leading to a reduction in nephron number. Little is known on the long-term consequences of in utero exposure to maternal diabetes. The aim of the study was to assess, in the rat, long-term effects of in utero exposure to maternal diabetes on blood pressure and renal function in adulthood.
4472. Pck1 gene silencing in the liver improves glycemia control, insulin sensitivity, and dyslipidemia in db/db mice.
作者: Alicia G Gómez-Valadés.;Andrés Méndez-Lucas.;Anna Vidal-Alabró.;Francese X Blasco.;Miguel Chillon.;Ramon Bartrons.;Jordi Bermúdez.;José C Perales.
来源: Diabetes. 2008年57卷8期2199-210页
Cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C; encoded by Pck1) catalyzes the first committed step in gluconeogenesis. Extensive evidence demonstrates a direct correlation between PEPCK-C activity and glycemia control. Therefore, we aimed to evaluate the metabolic impact and their underlying mechanisms of knocking down hepatic PEPCK-C in a type 2 diabetic model.
4473. Association analysis in african americans of European-derived type 2 diabetes single nucleotide polymorphisms from whole-genome association studies.
作者: Joshua P Lewis.;Nicholette D Palmer.;Pamela J Hicks.;Michele M Sale.;Carl D Langefeld.;Barry I Freedman.;Jasmin Divers.;Donald W Bowden.
来源: Diabetes. 2008年57卷8期2220-5页
Several whole-genome association studies have reported identification of type 2 diabetes susceptibility genes in various European-derived study populations. Little investigation of these loci has been reported in other ethnic groups, specifically African Americans. Striking differences exist between these populations, suggesting they may not share identical genetic risk factors. Our objective was to examine the influence of type 2 diabetes genes identified in whole-genome association studies in a large African American case-control population.
4474. Protein kinase C-delta mediates neuronal apoptosis in the retinas of diabetic rats via the Akt signaling pathway.
作者: Young-Hee Kim.;Yoon-Sook Kim.;Chang-Hwan Park.;In-Yong Chung.;Ji-Myong Yoo.;Jae-Geun Kim.;Byung-Ju Lee.;Sang-Soo Kang.;Gyeong-Jae Cho.;Wan-Sung Choi.
来源: Diabetes. 2008年57卷8期2181-90页
Protein kinase C (PKC)-delta, an upstream regulator of the Akt survival pathway, contributes to cellular dysfunction in the pathogenesis of diabetes. Herein, we examined the role of PKC-delta in neuronal apoptosis through Akt in the retinas of diabetic rats.
4475. Heritability of proliferative diabetic retinopathy.
作者: Kustaa Hietala.;Carol Forsblom.;Paula Summanen.;Per-Henrik Groop.; .
来源: Diabetes. 2008年57卷8期2176-80页
Diabetic nephropathy clusters in families, suggesting that genetic factors play a role in its pathogenesis. We investigated whether similar clustering exists for proliferative retinopathy in families with two or more siblings with type 1 diabetes.
4476. Autocrine IGF-1 action in adipocytes controls systemic IGF-1 concentrations and growth.
作者: Nora Klöting.;Linda Koch.;Thomas Wunderlich.;Matthias Kern.;Karen Ruschke.;Wilhelm Krone.;Jens C Brüning.;Matthias Blüher.
来源: Diabetes. 2008年57卷8期2074-82页
IGF-1 and the IGF-1 receptor (IGF-1R) have been implicated in the regulation of adipocyte differentiation and lipid accumulation in vitro.
4477. Activation of peroxisome proliferator-activated receptor beta/delta inhibits lipopolysaccharide-induced cytokine production in adipocytes by lowering nuclear factor-kappaB activity via extracellular signal-related kinase 1/2.
作者: Ricardo Rodríguez-Calvo.;Lucía Serrano.;Teresa Coll.;Norman Moullan.;Rosa M Sánchez.;Manuel Merlos.;Xavier Palomer.;Juan C Laguna.;Liliane Michalik.;Walter Wahli.;Manuel Vázquez-Carrera.
来源: Diabetes. 2008年57卷8期2149-57页
Chronic activation of the nuclear factor-kappaB (NF-kappaB) in white adipose tissue leads to increased production of pro-inflammatory cytokines, which are involved in the development of insulin resistance. It is presently unknown whether peroxisome proliferator-activated receptor (PPAR) beta/delta activation prevents inflammation in adipocytes.
4478. Evaluation of the association of IGF2BP2 variants with type 2 diabetes in French Caucasians.
作者: Konsta Duesing.;Ghazaleh Fatemifar.;Guillaume Charpentier.;Michel Marre.;Jean Tichet.;Serge Hercberg.;Beverley Balkau.;Philippe Froguel.;Fernando Gibson.
来源: Diabetes. 2008年57卷7期1992-6页
We performed a comprehensive genetic association study of common variation spanning the IGF2BP2 locus in order to replicate the association of the "confirmed" type 2 diabetes susceptibility variants rs4402960 and rs1470579 in the French Caucasian population and to further characterize the susceptibility variants at this novel locus.
4479. Association of FTO with obesity-related traits in the Cebu Longitudinal Health and Nutrition Survey (CLHNS) Cohort.
作者: Amanda F Marvelle.;Leslie A Lange.;Li Qin.;Linda S Adair.;Karen L Mohlke.
来源: Diabetes. 2008年57卷7期1987-91页
The underlying genetic component of obesity-related traits is not well understood, and there is limited evidence to support genetic association shared across multiple studies, populations, and environmental contexts. The present study investigated the association between candidate variants and obesity-related traits in a sample of 1,886 adult Filipino women from the Cebu Longitudinal Health and Nutrition Survey (CLHNS) cohort.
4480. Activation of estrogen receptor is crucial for resveratrol-stimulating muscular glucose uptake via both insulin-dependent and -independent pathways.
作者: Jen-Ying Deng.;Po-Shiuan Hsieh.;Jiung-Pang Huang.;Long-Sheng Lu.;Li-Man Hung.
来源: Diabetes. 2008年57卷7期1814-23页
Estradiol (E(2)) is known to modulate insulin sensitivity and, consequently, glucose homeostasis. Resveratrol (RSV), an agonist of estrogen receptor (ER), has exerted antihyperglycemic effects in streptozotocin-induced type 1 diabetic rats in our previous study and was also shown to improve insulin resistance in other reports. However, it remains unknown whether activation of ER is involved in the metabolic effects of RSV via insulin-dependent and -independent mechanisms.
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