Abstract

The first part of the project is concerned with the changes which take place in pancreatic B-cells when they are in a diabetic (hyperglycemic) milieu. It is hypothesized that chronic hyperglycemia produces marked changes in B-cell function and structure. Rat models will be used and these employ chemical and surgical reduction of B-cell mass, and glucose infusions. The focus will be upon insulin secretion and biosynthesis, and B-cell mass and growth capacity. These studies should provide new insights into the pathogenesis of diabetes mellitus. The second part of the project is concerned with the interrelationships which take place between the different cellular elements of islets. Studies will be carried out in human pancreatic tissue to determine the relationship of islet vasculature to the B-cell core and the non-B-cell mantle of islets. In addition, assessment will be made of polarity of A, B and D cells. These studies should further our understanding of the functional compartmentalization which is present in islets.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK035449-05
Application #
3233785
Study Section
Metabolism Study Section (MET)
Project Start
1984-09-01
Project End
1992-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
5
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Joslin Diabetes Center
Department
Type
DUNS #
071723084
City
Boston
State
MA
Country
United States
Zip Code
02215

  Publications

Goldfine, Allison B; Patti, Mary Elizabeth (2015) New lessons from gastric bypass: Impact of glucose-independent islet function. Obesity (Silver Spring) 23:1942-3
Lopez-Avalos, Maria D; Duvivier-Kali, Valerie F; Xu, Gang et al. (2006) Evidence for a role of the ubiquitin-proteasome pathway in pancreatic islets. Diabetes 55:1223-31
Weir, Gordon C; Bonner-Weir, Susan (2004) Five stages of evolving beta-cell dysfunction during progression to diabetes. Diabetes 53 Suppl 3:S16-21
Weir, Gordon C (2004) Can we make surrogate beta-cells better than the original? Semin Cell Dev Biol 15:347-57
Patane, Giovanni; Kaneto, Hideaki; Toschi, Elena et al. (2003) Induction of Mad expression leads to augmentation of insulin gene transcription. Biochem Biophys Res Commun 303:1199-208
Laybutt, D Ross; Glandt, Mariela; Xu, Gang et al. (2003) Critical reduction in beta-cell mass results in two distinct outcomes over time. Adaptation with impaired glucose tolerance or decompensated diabetes. J Biol Chem 278:2997-3005
Kaneto, Hideaki; Xu, Gang; Fujii, Nobuharu et al. (2002) Involvement of c-Jun N-terminal kinase in oxidative stress-mediated suppression of insulin gene expression. J Biol Chem 277:30010-8
Laybutt, D Ross; Weir, Gordon C; Kaneto, Hideaki et al. (2002) Overexpression of c-Myc in beta-cells of transgenic mice causes proliferation and apoptosis, downregulation of insulin gene expression, and diabetes. Diabetes 51:1793-804
Laybutt, D Ross; Kaneto, Hideaki; Hasenkamp, Wendy et al. (2002) Increased expression of antioxidant and antiapoptotic genes in islets that may contribute to beta-cell survival during chronic hyperglycemia. Diabetes 51:413-23
Laybutt, D Ross; Sharma, Arun; Sgroi, Dennis C et al. (2002) Genetic regulation of metabolic pathways in beta-cells disrupted by hyperglycemia. J Biol Chem 277:10912-21

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