The injection of streptozotocin(stz) at a high dose (60 mg/kg) into young male rats produces direct beta cell destruction and leads to insulin dependent diabetes (IDD). In contrast the injection of multiple smal doses of stz (40 mg/Kg/d for 5 days) produce IDD, which resembles type l diabetes in man. The provocative effects of the pertussis vaccine (PV) and cyclosporin(CA) against the development of IDD induced by stz were studied. When PV in a dose of 3.75 X 10(10) microorganism was administered to single or multiple stz treated rats, hyperglycemia still developed and persisted during the experiment. No difference was noted in blood glucose levels, but plasma insulin levels were higher in PV treated rats. When CA (10 mg/kg) was administered daily to single or multiple stz treated rats, hyperglycemia seemed to be lower, but this was not statistically significant, however, plasma insulin levels were higher in CA treated rats. The results of this experiment suggest that PV and CA provide some protection to the beta cells of the pancreas.
Animal ; Blood Glucose/metabolism ; Cyclosporins/pharmacology* ; Diabetes Mellitus, Experimental/prevention & control* ; Diabetes Mellitus, Insulin-Dependent/chemically induced ; Male ; Pertussis Vaccine/pharmacology* ; Rats ; Rats, Inbred Strains

Heart disease is one of the major cause of death in diabetic patients, but the thogenesis of diabetic cardio-myopathy remains unclear. In this experiment, to sess the significance of G protein signaling pathways in the pathogenesis of abetic cardiomyopathy, we analyzed the expression of G proteins and the tivities of second messenger dependent protein kinases: cAMP-dependent protein nase (PKA), DAG-mediated protein kinase C (PKC), and calmodulin dependent otein kinase II (CaM kinase II) in the streptozotocin induced diabetic rat art. The expression of Galphaq was increased by slightly over 10% (P<0.05) in abetic rat heart, while Galphas, Galphai, and Gbeta remained unchanged. The A activity in the heart did not change significantly but increased by 27%<0.01) in the liver. Insulin treatment did not restore the increased activity the liver. Total PKC activity in the heart was increased by 56% (P<0.01), and sulin treatment did not restore such increase. The CaM kinase II activity in e heart remained at the same level but was slightly increased in the liver 4% increase, P<0.05). These findings of increased expression of Galphaq in the reptozotocin-diabetic rat heart that are reflected by the increased level of C activity and insensitivity to insulin demonstrate that alteration of Galphaq y underlie, at least partly, the cardiac dysfunction that is associated with abetes. Copyright 2000 Academic Press.
Animal ; Ca(2+)-Calmodulin Dependent Protein Kinase/metabolism ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Diabetes Mellitus, Experimental/metabolism* ; Diabetes Mellitus, Experimental/drug therapy ; Diabetes Mellitus, Experimental/chemically induced ; GTP-Binding Proteins/metabolism* ; Insulin/pharmacology ; Liver/metabolism ; Liver/drug effects ; Male ; Myocardium/metabolism* ; Protein Kinase C/metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Streptozocin

BACKGROUND: It has been reported that many peripheral vasodilating drugs might improve insulin resistance. Cilostazol, a antithrombotic agent, increases peripheral blood flow in non-insulin dependent diabetic patients. The effect of cilostazol treatment on insulin resistance in streptozotocin (STZ)-induced non-insulin dependent diabetic Wistar rats was examined. METHODS: About a half of two-day old neonate siblings were injected intraperitoneally with STZ and maintained for six months, at which time they were compared with age-matched control rats for intraperitoneal glucose tolerance test (IPGTT) and for glucose infusion rate (GINF) in a euglycemic hyperinsulinemic glucose-clamp study. After that, these studies were also performed after feeding rat chow containing cilostazol (100 mg/kg/day) to rats with STZ-induced non-insulin dependent diabetes mellitus for four-weeks and compared with those of age-matched control rats. RESULTS: In the intraperitoneal glucose tolerance test studies, plasma glucose levels of STZ-induced non-insulin dependent diabetic rats were significantly higher and plasma insulin levels significantly lower than those of age-matched control rats in the age of six months. Glucose infusion rate was lower in STZ-induced non-insulin dependent diabetic rats than those of age-matched control rats. However, after a four-week cilostazol treatment, glucose infusion rate of STZ-induced non-insulin dependent diabetic rats was not significantly different from that of control rats. CONCLUSION: These findings suggested that cilostazol may improve insulin resistance in STZ-induced non-insulin dependent diabetic rats.
Animal ; Animals, Newborn ; Blood Glucose/*drug effects ; Comparative Study ; Diabetes Mellitus, Non-Insulin-Dependent/chemically induced/*drug therapy ; Disease Models, Animal ; Glucose Tolerance Test ; *Insulin Resistance ; Male ; Probability ; Rats ; Rats, Wistar ; Reference Values ; Sensitivity and Specificity ; Streptozocin ; Tetrazoles/*pharmacology ; Vasodilator Agents/*pharmacology