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Title: The handling of insulin by normal and diabetic kidneys
Author: Petersen, J.
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 1983
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The kidney plays a major role in the removal and degradation of low molecular weight proteins (LMWP, <40,000 daltons) with extraction from the renal circulation by glomerular filtration and peritubular uptake into the proximal tubular cell. The mechanisms involved in these processes and the alterations which occurs with uraemia, tubular proteinuric states and diabetes mellitus are reviewed with particular reference to one such LMWP, insulin. To further characterize these mechanisms the removal and metabolism of ¹²⁵I- insulin by isolated perfused nondiabetic and diabetic rat kidneys, brush border membranes vesicles and tissue homegenates were examined. It was concluded from these studies that the receptor mediated peritubular mechanism for insulin removal was temperature dependent and could compensate for the loss of the filtration - luminal - uptake pathway in the nondiabetc and diabetic kidneys but was impaired in the kidneys removed from hyperglycalcemic diabetic rats. All preparations similarly degraded insulin to both lower and larger molecular weight materials but partial degradation of insulin to a nonimmunoreactive product of similar molecular weight to insulin did not occur with brush border membrane vesicles. These vesicles had a major insulin specific receptor component with the ability to degrade insulin by a process exhibiting some specificity within the tubular membrane. Peritubular removal of insulin by kidneys from hyperglycalcemic diabetic rats was reduced whilst increased amounts of insulin were found in the final urine in all perfused diabetic kidneys. These results are discussed and confirm the findings of in vivo studies and are similar to the effects of diabetes in other target tissues. An understanding of these basic physiological and pathophysiological abnormalities in nondiabetic and diabetic states may lead to an increased understanding of diabetic nephropathy which is becoming an increasing problem to clinical nephrologists.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available