Alterations in renal hemodynamics in diabetes mellitus may result in glomerular damage. Since mesangial cells function as smooth muscle cells to regulate glomerular blood flow and filtration, perturbations in the contractile properties of these cells may result in disturbed glomerular function and glomerulosclerosis. Previous studies indicate that the renal vasculature and cultured mesangial cells show abnormal contraction and function in the diabetic state or under conditions which mimic diabetes. The purpose of the proposed studies is to characterize the biochemical events associated with mesangial cell contraction and examine how they may be altered by the diabetic state. The diabetic state will be studied on cells cultured from diabetic animals (streptozotocin and BB Wistar) and on cells cultured from normal animals exposed to a simulated diabetic milieu (i.e., high-glucose, insulin deficiency, and cellular myo-inositol deficiency). The studies to be performed are as follows: (1) Contraction/relaxation experiments using angiotensin II, arginine vasopressin, and catecholamines as the contractile agonists and PGE2 as the relaxing agonist; (2) intracellular Ca++ mobilization using the fluorescent Ca++-chelator Quin 2; (3) Cyclic AMP generation after stimulation with catecholamines; (4) Phosphorylation of contration-related proteins; (5) Examination of the cytoskeleton by immunofluorescence during contraction and relaxation; and (6) Arachidonic acid metabolism in mesangial cells obtained from BB Wistar diabetic and control rats. These studies should be beneficial in unraveling the pathogenesis of altered glomerular hemodynamics and glomerulosclerosis in diabetes mellitus.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
5R01AM029787-05
Application #
3151961
Study Section
Pathology A Study Section (PTHA)
Project Start
1981-08-01
Project End
1989-07-31
Budget Start
1985-08-01
Budget End
1986-07-31
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Type
Overall Medical
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
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Kreisberg, J I; Patel, P Y; Venkatachalam, M A et al. (1986) Elevations of intracellular cAMP result in a change in cell shape that resembles dome formation in cultured rat glomerular epithelial cells. In Vitro Cell Dev Biol 22:392-6
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Kreisberg, J I; Hassid, A (1986) Functional properties of glomerular cells in culture. Miner Electrolyte Metab 12:25-31
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Kreisberg, J I; Venkatachalam, M A (1986) Vasoactive agents affect mesangial cell adhesion. Am J Physiol 251:C505-11

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