Phenotypic correction of diabetic mice by adenovirus-mediated glucokinase expression.

Abstract:

:Hyperglycemia of diabetes is caused in part by perturbation of hepatic glucose metabolism. Hepatic glucokinase (GK) is an important regulator of glucose storage and disposal in the liver. GK levels are lowered in patients with maturity-onset diabetes of the young and in some diabetic animal models. Here, we explored the adenoviral vector-mediated overexpression of GK in a diet-induced murine model of type 2 diabetes as a treatment for diabetes. Diabetic mice were treated by intravenous administration with an E1/E2a/E3-deleted adenoviral vector encoding human hepatic GK (Av3hGK). Two weeks posttreatment, the Av3hGK-treated diabetic mice displayed normalized fasting blood glucose levels (95 +/- 4.8 mg/dl; P < 0.001) when compared with Av3Null (135 +/- 5.9 mg/dl), an analogous vector lacking a transgene, and vehicle-treated diabetic mice (134 +/- 8 mg/dl). GK treatment also resulted in lowered insulin levels (632 +/- 399 pg/ml; P < 0.01) compared with the control groups (Av3Null, 1,803 +/- 291 pg/ml; vehicle, 1,861 +/- 392 pg/ml), and the glucose tolerance of the Av3hGK-treated diabetic mice was normalized. No significant increase in plasma or hepatic triglycerides, or plasma free fatty acids was observed in the Av3hGK-treated mice. These data suggest that overexpression of GK may have a therapeutic potential for the treatment of type 2 diabetes.

journal_name

Diabetes

journal_title

Diabetes

authors

Desai UJ,Slosberg ED,Boettcher BR,Caplan SL,Fanelli B,Stephan Z,Gunther VJ,Kaleko M,Connelly S

doi

10.2337/diabetes.50.10.2287

subject

Has Abstract

pub_date

2001-10-01 00:00:00

pages

2287-95

issue

10

eissn

0012-1797

issn

1939-327X

journal_volume

50

pub_type

杂志文章

相关文献

DIABETES文献大全
  • Autoantibodies to islet cells in diabetes mellitus.

    abstract::Numerous reports have confirmed the presence of islet cell antibodies in diabetic patients. These are found mostly in newly diagnosed insulin-dependent diabetic patients and in patients who have autoimmune polyendocrine disorders. Antibodies to beta cells, somatostatin, and glucagon-producing cells have been described...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.28.2.102

    authors: Kaldany A

    更新日期:1979-02-01 00:00:00

  • Effect of genetic obesity in mice on the induction of diabetes by encephalomyocarditis virus.

    abstract::The "M" variant of the encephalomyocarditis (EMC) virus causes a diabetes-like disease in some, but not all, strains of mice. The genetic basis for either resistance or susceptibility to the diabetogenic effect of the virus is not known. After infection with EMC, C57BL/6 mice seldom develop hyperglycemia and the insul...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.30.5.451

    authors: D'Andrea BJ,Wilson GL,Craighead JE

    更新日期:1981-05-01 00:00:00

  • 6-Phosphogluconate/glucose-6-phosphate ratio in rat pancreatic islets during inhibition of insulin release by exogenous insulin.

    abstract::Inhibition of glucose-stimulated insulin release by exogenous insulin has been demonstrated in pancreatic islets to be associated with a decrease of the NADPH/NADP ratio and the pentose-phosphate cycle activity. Batches of five islets were incubated for 15 and 90 minutes in 1 ml. of KRB buffer with 2 per cent albumin ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.26.9.857

    authors: Akhtar MS,Verspohl E,Hegner D,Ammon HP

    更新日期:1977-09-01 00:00:00

  • Association testing of novel type 2 diabetes risk alleles in the JAZF1, CDC123/CAMK1D, TSPAN8, THADA, ADAMTS9, and NOTCH2 loci with insulin release, insulin sensitivity, and obesity in a population-based sample of 4,516 glucose-tolerant middle-aged Danes.

    abstract:OBJECTIVE:We evaluated the impact on diabetes-related intermediary traits of common novel type 2 diabetes-associated variants in the JAZF1 (rs864745), CDC123/CAMK1D (rs12779790), TSPAN8 (rs7961581), THADA (rs7578597), ADAMTS9 (rs4607103), and NOTCH2 (rs10923931) loci, which were recently identified by meta-analysis of ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db08-0436

    authors: Grarup N,Andersen G,Krarup NT,Albrechtsen A,Schmitz O,Jørgensen T,Borch-Johnsen K,Hansen T,Pedersen O

    更新日期:2008-09-01 00:00:00

  • In vivo chloroquine-induced inhibition of insulin degradation in a diabetic patient with severe insulin resistance.

    abstract::We report on a 26-yr-old patient with an 11-yr history of insulin-dependent diabetes mellitus who exhibited insulin resistance with a requirement of up to 15,000 U of intravenous (i.v.) insulin/day. Attempts to diminish her insulin requirement by administration of sulfated insulin or Trasylol were unsuccessful, with t...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.33.12.1133

    authors: Blazar BR,Whitley CB,Kitabchi AE,Tsai MY,Santiago J,White N,Stentz FB,Brown DM

    更新日期:1984-12-01 00:00:00

  • New monoclonal antibody diagnostic reagents for type I diabetes: differential lymphocyte surface antigen expression related to disease.

    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

    pub_type: 杂志文章

    doi:10.2337/diab.46.3.363

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

    更新日期:1997-03-01 00:00:00

  • Evaluation of polymorphic splicing in the mechanism of the association of the insulin gene with diabetes.

    abstract::The association of type 1 diabetes with the insulin gene (IDDM2 locus) has been mapped to a short haplotype encompassing two single nucleotide polymorphisms (SNPs) in perfect linkage disequilibrium (r(2) = 1) with each other and with the two allele classes at the variable number of tandem repeats (VNTR) polymorphism u...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db06-0402

    authors: Marchand L,Polychronakos C

    更新日期:2007-03-01 00:00:00

  • Conference on insulin pump therapy in diabetes. Multicenter study effect on microvascular disease. Studies of retinopathy. Methodology for assessment and classification with fundus photographs.

    abstract::A major goal of the study was to assess the methodologies available for the quantification of retinal lesions suitable for application in trials of metabolic management. We describe the methods used for grading stereoscopic color fundus photographs. Overall retinopathy severity level for each eye ranging from normal (...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.34.3.s42

    authors: Davis MD,Hubbard LD,Trautman J,Klein R

    更新日期:1985-08-01 00:00:00

  • Progression of incipient diabetic retinopathy during good glycemic control.

    abstract::To assess the extent to which the progression of diabetic retinopathy can be arrested by improved glycemic control, 35 normal dogs were randomly divided into a nondiabetic and three alloxan-induced diabetic groups prospectively identified according to glycemic control: poor control for 5 yr (PC), good control for 5 yr...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.36.7.808

    authors: Engerman RL,Kern TS

    更新日期:1987-07-01 00:00:00

  • Interaction of interleukin-1 with islet beta-cells. Distinction between indirect, aspecific cytotoxicity and direct, specific functional suppression.

    abstract::A 5-day culture of adult rat islets with human recombinant IL-1 beta (3 U/ml) resulted in the death of most alpha-cells and 50% of beta-cells. The IL-1--exposed islet tissue contained--in addition to poorly granulated beta-cells--patches of outgrowing monolayers and dispersed activated macrophages. In purified alpha- ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.42.1.56

    authors: Ling Z,In't Veld PA,Pipeleers DG

    更新日期:1993-01-01 00:00:00

  • NeuroD/BETA2 gene variability and diabetes: no associations to late-onset type 2 diabetes but an A45 allele may represent a susceptibility marker for type 1 diabetes among Danes. Danish Study Group of Diabetes in Childhood, and the Danish IDDM Epidemiolog

    abstract::Mutations in the NeuroD/BETA2 gene have been shown to associate with type 2 diabetes. In the present study, we examined mutations in the NeuroD/BETA2 gene for association with either type 1 or 2 diabetes. Three variants were identified in patients with type 2 diabetes: Ala45Thr (allelic frequency 0.36, 95% CI 0.31-0.4...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.49.5.876

    authors: Hansen L,Jensen JN,Urioste S,Petersen HV,Pociot F,Eiberg H,Kristiansen OP,Hansen T,Serup P,Nerup J,Pedersen O

    更新日期:2000-05-01 00:00:00

  • Circulating adiponectin levels are reduced in nonobese but insulin-resistant first-degree relatives of type 2 diabetic patients.

    abstract::Adiponectin, one of the most abundant gene transcript proteins in human fat cells, has been shown to improve insulin action and is also suggested to exert antiatherogenic effects. We measured circulating adiponectin levels and risk factors for atherosclerosis in 45 healthy first-degree relatives of type 2 diabetic sub...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.52.5.1182

    authors: Pellmé F,Smith U,Funahashi T,Matsuzawa Y,Brekke H,Wiklund O,Taskinen MR,Jansson PA

    更新日期:2003-05-01 00:00:00

  • Decreased cardiac glutathione peroxidase levels and enhanced mandibular apoptosis in malformed embryos of diabetic rats.

    abstract:OBJECTIVE:To characterize normal and malformed embryos within the same litters from control and diabetic rats for expression of genes related to metabolism of reactive oxygen species (ROS) or glucose as well as developmental genes. RESEARCH DESIGN AND METHODS:Embryos from nondiabetic and streptozotocin-induced diabeti...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db08-0830

    authors: Wentzel P,Gäreskog M,Eriksson UJ

    更新日期:2008-12-01 00:00:00

  • Liver sinusoidal endothelial cells link hyperinsulinemia to hepatic insulin resistance.

    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

    pub_type: 杂志文章

    doi:10.2337/db12-1296

    authors: Tsuchiya K,Accili D

    更新日期:2013-05-01 00:00:00

  • Analysis of the mouse CD30 gene: a candidate for the NOD mouse type 1 diabetes locus Idd9.2.

    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

    pub_type: 杂志文章

    doi:10.2337/diabetes.49.9.1612

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

    更新日期:2000-09-01 00:00:00

  • Storage of circulating free fatty acid in adipose tissue of postabsorptive humans: quantitative measures and implications for body fat distribution.

    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

    pub_type: 杂志文章

    doi:10.2337/db11-0154

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

    更新日期:2011-08-01 00:00:00

  • Salutary effect of pigment epithelium-derived factor in diabetic nephropathy: evidence for antifibrogenic activities.

    abstract::Diabetic nephropathy is a major complication of diabetes and a leading cause of end-stage renal diseases in the U.S. Pigment epithelium-derived factor (PEDF) is a potent angiogenic inhibitor that has been extensively studied in diabetic retinopathy. Recently, we reported that PEDF is expressed at high levels in normal...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db05-1448

    authors: Wang JJ,Zhang SX,Mott R,Knapp RR,Cao W,Lau K,Ma JX

    更新日期:2006-06-01 00:00:00

  • Metabolic effects of long-acting somatostatin analogue (sandostatin) in type I diabetic patients on conventional therapy.

    abstract::We evaluated the effectiveness of a more potent and longer-acting somatostatin analogue (SMS 201-995) as an adjunct to insulin therapy, in a double-blind placebo-controlled randomized study of 26 C-peptide-negative type I (insulin-dependent) diabetic patients (20 women, 6 men, aged 22-40 yr) on their conventional drug...

    journal_title:Diabetes

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.2337/diab.38.6.704

    authors: Osei K,O'Dorisio TM,Malarkey WB,Craig EL,Cataland S

    更新日期:1989-06-01 00:00:00

  • Dietary cod protein restores insulin-induced activation of phosphatidylinositol 3-kinase/Akt and GLUT4 translocation to the T-tubules in skeletal muscle of high-fat-fed obese rats.

    abstract::Diet-induced obesity is known to cause peripheral insulin resistance in rodents. We have recently found that feeding cod protein to high-fat-fed rats prevents the development of insulin resistance in skeletal muscle. In the present study, we have further explored the cellular mechanisms behind this beneficial effect o...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.52.1.29

    authors: Tremblay F,Lavigne C,Jacques H,Marette A

    更新日期:2003-01-01 00:00:00

  • Functional analysis of a conditionally transformed pancreatic beta-cell line.

    abstract::Development of beta-cell lines for cell therapy of diabetes is hindered by functional deviations of the replicating cells from the normal beta-cell phenotype. In a recently developed cell line, denoted betaTC-tet, derived from transgenic mice expressing the SV40 T antigen (Tag) under control of the tetracycline (Tc) g...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.47.9.1419

    authors: Fleischer N,Chen C,Surana M,Leiser M,Rossetti L,Pralong W,Efrat S

    更新日期:1998-09-01 00:00:00

  • The Metabolic Regulator Histone Deacetylase 9 Contributes to Glucose Homeostasis Abnormality Induced by Hepatitis C Virus Infection.

    abstract::Class IIa histone deacetylases (HDACs), such as HDAC4, HDAC5, and HDAC7, provide critical mechanisms for regulating glucose homeostasis. Here we report that HDAC9, another class IIa HDAC, regulates hepatic gluconeogenesis via deacetylation of a Forkhead box O (FoxO) family transcription factor, FoxO1, together with HD...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db15-0197

    authors: Chen J,Wang N,Dong M,Guo M,Zhao Y,Zhuo Z,Zhang C,Chi X,Pan Y,Jiang J,Tang H,Niu J,Yang D,Li Z,Han X,Wang Q,Chen X

    更新日期:2015-12-01 00:00:00

  • Two novel immortal pancreatic beta-cell lines expressing and secreting human islet amyloid polypeptide do not spontaneously develop islet amyloid.

    abstract::Type 2 diabetes is characterized by islet amyloid deposits, which are primarily composed of the amyloidogenic human form of islet amyloid polypeptide (IAPP, amylin). The mechanism of islet amyloido-genesis is not known, but other products (e.g., apolipoprotein E and perlecan) contained within islet amyloid may be nece...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.48.10.1962

    authors: Andrikopoulos S,Verchere CB,Teague JC,Howell WM,Fujimoto WY,Wight TN,Kahn SE

    更新日期:1999-10-01 00:00:00

  • The ATP-sensitive K(+) channel ABCC8 S1369A type 2 diabetes risk variant increases MgATPase activity.

    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

    pub_type: 杂志文章

    doi:10.2337/db11-0371

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

    更新日期:2012-01-01 00:00:00

  • Adipose tissue TCF7L2 splicing is regulated by weight loss and associates with glucose and fatty acid metabolism.

    abstract::We investigated the effects of obesity surgery-induced weight loss on transcription factor 7-like 2 gene (TCF7L2) alternative splicing in adipose tissue and liver. Furthermore, we determined the association of TCF7L2 splicing with the levels of plasma glucose and serum free fatty acids (FFAs) in three independent stud...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db12-0239

    authors: Kaminska D,Kuulasmaa T,Venesmaa S,Käkelä P,Vaittinen M,Pulkkinen L,Pääkkönen M,Gylling H,Laakso M,Pihlajamäki J

    更新日期:2012-11-01 00:00:00

  • Long-term AICAR administration reduces metabolic disturbances and lowers blood pressure in rats displaying features of the insulin resistance syndrome.

    abstract::The insulin resistance syndrome is characterized by several risk factors for cardiovascular disease. Chronic chemical activation of AMP-activated protein kinase by the adenosine analog 5-aminoimidazole-4-carboxamide-1-beta -D-ribofuranoside (AICAR) has been shown to augment insulin action, upregulate mitochondrial enz...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.51.7.2199

    authors: Buhl ES,Jessen N,Pold R,Ledet T,Flyvbjerg A,Pedersen SB,Pedersen O,Schmitz O,Lund S

    更新日期:2002-07-01 00:00:00

  • Dipeptidyl peptidase IV inhibition reduces the degradation and clearance of GIP and potentiates its insulinotropic and antihyperglycemic effects in anesthetized pigs.

    abstract::Glucose-dependent insulinotropic peptide (GIP) is known to be degraded by dipeptidyl peptidase IV (DPP IV), forming an inactive metabolite, but the extent of the enzyme's role in regulating the biological activity of GIP in vivo is still largely unknown. In nonfasted anesthetized pigs given an intravenous infusion of ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.50.7.1588

    authors: Deacon CF,Danielsen P,Klarskov L,Olesen M,Holst JJ

    更新日期:2001-07-01 00:00:00

  • ZnT8 is a major CD8+ T cell-recognized autoantigen in pediatric type 1 diabetes.

    abstract::Type 1 diabetes results from the destruction of β-cells by an autoimmune T-cell response assisted by antigen-presenting B cells producing autoantibodies. CD8(+) T-cell responses against islet cell antigens, thought to play a central role in diabetes pathogenesis, can be monitored using enzyme-linked immunosorbent spot...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db12-0071

    authors: Énée É,Kratzer R,Arnoux JB,Barilleau E,Hamel Y,Marchi C,Beltrand J,Michaud B,Chatenoud L,Robert JJ,van Endert P

    更新日期:2012-07-01 00:00:00

  • Intraislet Ghrelin Signaling Does Not Regulate Insulin Secretion From Adult Mice.

    abstract::Exogenous ghrelin reduces glucose-stimulated insulin secretion and endogenous ghrelin protects against hypoglycemia during starvation. Islet ε-cells produce ghrelin and δ-cells express growth hormone secretagogue receptor (GHSR), suggesting the possibility of a paracrine mechanism for islet ghrelin to reach high local...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db19-0079

    authors: Gray SM,Niu J,Zhang A,Svendsen B,Campbell JE,D'Alessio DA,Tong J

    更新日期:2019-09-01 00:00:00

  • Association of Organic Cation Transporter 1 With Intolerance to Metformin in Type 2 Diabetes: A GoDARTS Study.

    abstract::Metformin is the most widely prescribed medication for the treatment of type 2 diabetes (T2D). However, gastrointestinal (GI) side effects develop in ~25% of patients treated with metformin, leading to the discontinuation of therapy in ~5% of cases. We hypothesized that reduced transport of metformin via organic catio...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db14-1388

    authors: Dujic T,Zhou K,Donnelly LA,Tavendale R,Palmer CN,Pearson ER

    更新日期:2015-05-01 00:00:00

  • Carotid artery intima-media thickness in children with type 1 diabetes.

    abstract::Postmortem studies have shown a relationship between diabetic state and atherosclerotic arterial lesions in adolescents. The aim of the present study was to determine the presence of increased subclinical atherosclerosis (measured as carotid intima-media thickness [IMT]) and its risk factors, including lipoprotein oxi...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.51.2.493

    authors: Järvisalo MJ,Putto-Laurila A,Jartti L,Lehtimäki T,Solakivi T,Rönnemaa T,Raitakari OT

    更新日期:2002-02-01 00:00:00