Mechanisms of diabetes mellitus induced with FK506 in SD rats models.
BACKGROUND
Tacrolimus causes post-transplant diabetes mellitus, however the pathogenetic mechanisms remain controversial. In this study we probed into the mechanisms of tacrolimus-induced diabetes mellitus in rats.


METHODS
Glucose levels were determined on whole blood samples using a glucose oxidase method. Levels of serum insulin and C-peptide were measured with ELISA. Histological damage of ultra-structure and apoptosis of beta cells of the pancreas were assayed with electric microscope and tunnel methods respectively.--Ultra-structure were assayed with electric microscope and apoptosis of beta cells of the pancreas were assayed with tunnel methods. Immunohistochemistry was utilized to detect the sum of insulin receptors of hepatic cells.


RESULTS
Compared to control group, insulin and C peptide levels in serum decreased in rats of diabetes mellitus models induced with FK506(P<0.05). Compared to the control group, the sum of apoptosis body in pancreatic islets increased in rats of diabetes mellitus models induced with FK506 (P<0.05). Compared to the control group, electron microscopy showed cytoplasm swelling and vacuolization, and marked decrease or absence of dense-core secretory granules in beta cells in rats with diabetes mellitus induced with FK506.Compared to the control group, expression of insulin receptor of hepatic cell decreased in rats of diabetes mellitus models induced with FK506 (P<0.05).


CONCLUSIONS
Pathogenetic mechanisms of rats of diabetes mellitus models induced with FK506 including reduction of secretion of insulin in beta cells of pancreatic islets, damages of ultra-structure of beta cells of pancreatic islets, increasing of apoptosis of beta cells of pancreatic islets and decreasing of expression of insulin receptors in hepatic cells.
Li
Qing Yuan
QY
Department of Urology and Transplantation, First Affiliated Hospital, Binzhou Medical University, Binzhou City, Shandong Province, China. lqy999496@yahoo.com.cn
Li
Feng
F
Sun
Ji Hua
JH
Chi
Yu You
YY
Yin
Hong Shan
HS
Liu
Shao Qing
SQ
Mei
Yan Hui
YH
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced* / Q000473:pathology; D004195:Disease Models, Animal; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007329:Insulin Antagonists / Q000008:administration & dosage / Q000633:toxicity; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016559:Tacrolimus / Q000008:administration & dosage / Q000633:toxicity*
D007328:Insulin; D007329:Insulin Antagonists; D016559:Tacrolimus