RENAL FUNCTION IN DIABETES MELLITUS AND THE ROLE OF NITRIC OXIDE IN ALTERED FLUID BALANCE STATES
Although previous studies have described a mouse model for diet-induced Type II diabetes mellitus, renal function in these animals has not been characterized. The aim of the first study of this thesis was to measure cardiovascular and renal function, including the renal transport capacity for glucose, in male and female C57BL/6J mice with diet-induced Type II diabetes mellitus. Results from the first portion of the thesis indicated that C57BL/6J mice are valuable tools for studying diet-induced obesity, hyperglycemia, and hyperinsulinemia; however, no hypertension or kidney dysfunction is apparent within the time frame (3 – 6 months) of the current study. Information regarding the renal glucose transport capacity in diabetes mellitus is limited. These data are needed because two weeks following injection of streptozotocin (STZ), mRNA and protein levels of the glucose transporter, GLUT2, are upregulated in the proximal tubule of the rat. In the second part of the thesis renal glucose transport and GLUT2 protein levels were measured in female control rats, and in rats one (STZ-1), two (STZ-2), and three weeks (STZ-3) after STZ injection (65 mg kg-1, ip). Data from these studies suggest that other factors, functioning either in conjunction with or independent of GLUT2, are required to support an elevated renal glucose transport capacity. The final part of the thesis was designed to determine to what extent nitric oxide (NO) mediates the natriuretic and diuretic responses to acute isotonic saline volume expansion (SVE). Studies were performed on pentobarbital anesthetized female Sprague-Dawley rats with or without a NO synthase inhibitor, Nw-nitro-L-arginine (LNA). The data demonstrate that 1) NO does not mediate SVE-induced hyperfiltration in the rat, 2) NO also does not mediate SVE-induced natriuresis or diuresis, and 3), consistent with other reports, NO appears to mediate pressure natriuresis and diuresis.
School:University of Cincinnati
School Location:USA - Ohio
Source Type:Master's Thesis
Keywords:type ii diabetes c57 bl 6j mouse glucose transport nitric oxide saline volume expansion
Date of Publication:01/01/2000