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Insulin-induced immunohistochemical and morphological changes in pancreatic beta-cells of streptozotocin-treated diabetic rats

S O Adewole, J A O Ojewole
Methods and Findings in Experimental and Clinical Pharmacology 2007, 29 (7): 447-55
17982509
This study was undertaken to investigate insulin-induced changes in the immunohistochemistry and morphometry of pancreatic beta-cells, plasma insulin and blood glucose concentrations of streptozotocin (STZ)-treated diabetic rats. Fifty male Wistar rats (200-250 g) were randomly divided into three experimental groups (viz., A: control group, B: STZ-treated group, and C: STZ+insulin-treated group). Diabetes was induced in group B and group C rats by single intraperitoneal injections of STZ (75 mg/kg body weight), while each animal in the "control" group A received equal volume of citrate buffer solution (pH 6.3) intraperitoneally. STZ+insulin-treated group C diabetic rats were additionally treated with subcutaneous injections of lente insulin (0.5 U/kg body weight) daily from Day 10 to Day 30 of our 40-day study period. The rats used were sacrificed at different time intervals (10th, 20th, 30th and up to the 40th day) following STZ treatment. Fragments of endocrine pancreas of each rat were randomly processed for immunohistochemistry staining and pancreatic insulin content. In diabetic state, pancreatic beta-cells showed a weak immunostaining for insulin on Day 10. Thereafter, insulin administration (in the group C rats) caused a significant decrease (p < 0.05) in the elevated blood glucose levels, and a significant increase (p < 0.05) in the serum insulin concentrations. The surviving beta-cells regenerated and virtually regained their normal immunostaining and functional status for insulin. On the 30th day, the pancreatic insulin contents of the insulin-treated group C rats showed approximately 45-fold increase in immunoreactivity when compared with the immunoreactivity of the same STZ+insulin-treated rats on Day 10 of the 40-day study period. The present study illustrates the sequence of morphological changes that occur in the islets of Langerhans following STZ administration and subsequent insulin treatment. The study also suggests that administration of a moderate single dose of STZ in Wistar rats produces specific necrosis of beta-cells, typical of type 1 insulin-dependent diabetes. The experimental evidence obtained in this study appears to suggest that induction of regenerative stimulus (by insulin treatment) in diabetic state triggers pancreatic regenerative processes, thereby restoring functional activities of the pancreas.

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