Literature DB >> 9435258

OB-Rb gene transfer to leptin-resistant islets reverses diabetogenic phenotype.

M Y Wang1, K Koyama, M Shimabukuro, C B Newgard, R H Unger.   

Abstract

In obese Zucker diabetic fatty (ZDF) rats with mutant leptin receptors, pancreatic islets have an approximately 50-fold increase in fat (TG), overproduce nitric oxide (NO), and lack a normal proinsulin mRNA response to fatty acids. We overexpressed the wild-type full-length "b" isoform of the leptin receptor (OB-Rb) in ZDF islets by perfusing ZDF pancreata with recombinant adenovirus containing the cDNA encoding OB-Rb. In cultured islets isolated from these animals, leptin lowered islet TG by 87% and completely blocked TG formation from free fatty acids. Overproduction of NO was reduced, and the preproinsulin mRNA response to free fatty acids was restored. This establishes defective leptin action as the proximate cause of lipotoxic diabetes in ZDF rats.

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Year:  1998        PMID： 9435258      PMCID： PMC18486          DOI： 10.1073/pnas.95.2.714

Source DB:  PubMed          Journal:  Proc Natl Acad Sci U S A        ISSN： 0027-8424            Impact factor:   11.205


  22 in total

1.  Leptin- or troglitazone-induced lipopenia protects islets from interleukin 1beta cytotoxicity.

Authors:  M Shimabukuro; K Koyama; Y Lee; R H Unger
Journal:  J Clin Invest       Date:  1997-10-01       Impact factor: 14.808

2.  Induction by leptin of uncoupling protein-2 and enzymes of fatty acid oxidation.

Authors:  Y T Zhou; M Shimabukuro; K Koyama; Y Lee; M Y Wang; F Trieu; C B Newgard; R H Unger
Journal:  Proc Natl Acad Sci U S A       Date:  1997-06-10       Impact factor: 11.205

3.  Role of nitric oxide in obesity-induced beta cell disease.

Authors:  M Shimabukuro; M Ohneda; Y Lee; R H Unger
Journal:  J Clin Invest       Date:  1997-07-15       Impact factor: 14.808

4.  Undiagnosed NIDDM: clinical and public health issues.

Authors:  M I Harris
Journal:  Diabetes Care       Date:  1993-04       Impact factor: 19.112

Review 5.  Use of recombinant adenovirus for metabolic engineering of mammalian cells.

Authors:  T C Becker; R J Noel; W S Coats; A M Gómez-Foix; T Alam; R D Gerard; C B Newgard
Journal:  Methods Cell Biol       Date:  1994       Impact factor: 1.441

6.  Direct antidiabetic effect of leptin through triglyceride depletion of tissues.

Authors:  M Shimabukuro; K Koyama; G Chen; M Y Wang; F Trieu; Y Lee; C B Newgard; R H Unger
Journal:  Proc Natl Acad Sci U S A       Date:  1997-04-29       Impact factor: 11.205

7.  Leptin receptor missense mutation in the fatty Zucker rat.

Authors:  M S Phillips; Q Liu; H A Hammond; V Dugan; P J Hey; C J Caskey; J F Hess
Journal:  Nat Genet       Date:  1996-05       Impact factor: 38.330

8.  Caloric restriction in obese pre-diabetic rats prevents beta-cell depletion, loss of beta-cell GLUT 2 and glucose incompetence.

Authors:  M Ohneda; L R Inman; R H Unger
Journal:  Diabetologia       Date:  1995-02       Impact factor: 10.122

Review 9.  Disordered metabolism in diabetes: have we underemphasized the fat component?

Authors:  J D McGarry
Journal:  J Cell Biochem       Date:  1994       Impact factor: 4.429

10.  How obesity causes diabetes in Zucker diabetic fatty rats.

Authors:  R H Unger
Journal:  Trends Endocrinol Metab       Date:  1997-09       Impact factor: 12.015
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  19 in total

1.  Regulation of fatty acid homeostasis in cells: novel role of leptin.

Authors:  R H Unger; Y T Zhou; L Orci
Journal:  Proc Natl Acad Sci U S A       Date:  1999-03-02       Impact factor: 11.205

2.  Thyroid hormone drives fetal cardiomyocyte maturation.

Authors:  Natasha N Chattergoon; George D Giraud; Samantha Louey; Philip Stork; Abigail L Fowden; Kent L Thornburg
Journal:  FASEB J       Date:  2011-10-05       Impact factor: 5.191

3.  Effects of conjugated linoleic acid and troglitazone on lipid accumulation and composition in lean and Zucker diabetic fatty (fa/fa) rats.

Authors:  Angela A Wendel; Martha A Belury
Journal:  Lipids       Date:  2006-03       Impact factor: 1.880

4.  Leptin increases serotonin turnover by inhibition of brain nitric oxide synthesis.

Authors:  G Calapai; F Corica; A Corsonello; L Sautebin; M Di Rosa; G M Campo; M Buemi; V N Mauro; A P Caputi
Journal:  J Clin Invest       Date:  1999-10       Impact factor: 14.808

5.  Resistance to adenovirally induced hyperleptinemia in rats. Comparison of ventromedial hypothalamic lesions and mutated leptin receptors.

Authors:  K Koyama; M Shimabukuro; G Chen; M Y Wang; Y Lee; P S Kalra; M G Dube; S P Kalra; C B Newgard; R H Unger
Journal:  J Clin Invest       Date:  1998-08-15       Impact factor: 14.808

6.  Protection against lipoapoptosis of beta cells through leptin-dependent maintenance of Bcl-2 expression.

Authors:  M Shimabukuro; M Y Wang; Y T Zhou; C B Newgard; R H Unger
Journal:  Proc Natl Acad Sci U S A       Date:  1998-08-04       Impact factor: 11.205

7.  Hyperleptinemia prevents lipotoxic cardiomyopathy in acyl CoA synthase transgenic mice.

Authors:  Young Lee; R Haris Naseem; Laurence Duplomb; Byung-Hyun Park; Daniel J Garry; James A Richardson; Jean E Schaffer; Roger H Unger
Journal:  Proc Natl Acad Sci U S A       Date:  2004-09-03       Impact factor: 11.205

8.  Differential expression of the insulin gene transcriptional repressor CCAAT/enhancer-binding protein beta and transactivator islet duodenum homeobox-1 in rat pancreatic beta cells during the development of diabetes mellitus.

Authors:  J Seufert; G C Weir; J F Habener
Journal:  J Clin Invest       Date:  1998-06-01       Impact factor: 14.808

9.  Overexpression of leptin receptors in pancreatic islets of Zucker diabetic fatty rats restores GLUT-2, glucokinase, and glucose-stimulated insulin secretion.

Authors:  M Y Wang; K Koyama; M Shimabukuro; D Mangelsdorf; C B Newgard; R H Unger
Journal:  Proc Natl Acad Sci U S A       Date:  1998-09-29       Impact factor: 11.205

10.  Role of peroxisome proliferator-activated receptor alpha in disease of pancreatic beta cells.

Authors:  Y T Zhou; M Shimabukuro; M Y Wang; Y Lee; M Higa; J L Milburn; C B Newgard; R H Unger
Journal:  Proc Natl Acad Sci U S A       Date:  1998-07-21       Impact factor: 11.205
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