Abstract

The broad objective of this research program is to gain understanding of the nature of diabetes mellitus in humans, particularly with regard to etiology and to mechanisms of pathological, physiological, and biochemical changes. The proposed approach to the pathobiology of diabetes mellitus focuses on four major interrelated areas: 1. insulin secretion; 2. insulin action; 3. the pathogenesis of different forms of diabetes; and 4. the pathogenesis of atherosclerosis in diabetes. Projects are proposed to study the role of prostaglandins in pancreatic islet function, regulation of prostaglandin-E receptors in pancreatic islets and adipocytes, studies of oscillatory secretion of somatostatin, mechanism of action of insulin on cell membranes, regulation of the function of lysosomes in diabetes, factors influencing the pathogenesis of insulin-dependent diabetes, obesity and adipose tissue lipoprotein lipase activity, particularly in relation to non-insulin dependent diabetes, the interactions of human arterial cells with lipoproteins, and the regulation of arterial cell metabolism in diabetes, and a common project involving several investigators focused on lipoprotein abnormalities in diabetes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Program Projects (P01)
Project #
5P01AM002456-27
Application #
3092239
Study Section
(SRC)
Project Start
1976-09-01
Project End
1986-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
27
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of Washington
Department
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

Francis, B H; Baskin, D G; Saunders, D R et al. (1990) Distribution of somatostatin-14 and somatostatin-28 gastrointestinal-pancreatic cells of rats and humans. Gastroenterology 99:1283-91
D'Alessio, D A; Sieber, C; Beglinger, C et al. (1989) A physiologic role for somatostatin 28 as a regulator of insulin secretion. J Clin Invest 84:857-62
Ensinck, J W; Laschansky, E C; Vogel, R E et al. (1989) Circulating prosomatostatin-derived peptides. Differential responses to food ingestion. J Clin Invest 83:1580-9
Auwerx, J H; Chait, A; Deeb, S S (1989) Regulation of the low density lipoprotein receptor and hydroxymethylglutaryl coenzyme A reductase genes by protein kinase C and a putative negative regulatory protein. Proc Natl Acad Sci U S A 86:1133-7
Phillips, P E; Lipkin, E W; de Haen, C (1988) Enhancement of insulin binding to rat white adipocytes at 15 degrees C by 5,5'-dithiobis-(2-nitrobenzoic acid). Independence of the reagent's sulfhydryl group reactivity. J Biol Chem 263:11175-82
Oppenheimer, M J; Oram, J F; Bierman, E L (1988) Up-regulation of high density lipoprotein receptor activity by gamma-interferon associated with inhibition of cell proliferation. J Biol Chem 263:19318-23
White, J R; Chait, A; Klebanoff, S J et al. (1988) Bacterial lipopolysaccharide reduces macrophage lipoprotein lipase levels: an effect that is independent of tumor necrosis factor. J Lipid Res 29:1379-85
Ahn, N G; Teller, D C; Bienkowski, M J et al. (1988) Sedimentation equilibrium analysis of five lipocortin-related phospholipase A2 inhibitors from human placenta. Evidence against a mechanistically relevant association between enzyme and inhibitor. J Biol Chem 263:18657-63
Aviram, M; Lund-Katz, S; Phillips, M C et al. (1988) The influence of the triglyceride content of low density lipoprotein on the interaction of apolipoprotein B-100 with cells. J Biol Chem 263:16842-8
Chait, A; Ross, R; Bierman, E L (1988) Stimulation of receptor-dependent and receptor-independent pathways of low-density lipoprotein degradation in arterial smooth muscle cells by platelet-derived growth factor. Biochim Biophys Acta 960:183-9

Showing the most recent 10 out of 41 publications