Streptozotocin alters pancreatic beta-cell responsiveness to glucose within six hours of injection into rats

A 24-hour glycaemic profile following streptozotocin (80 mg/kg. ip) injection was investigated in fasted rats. The most prominent changes in blood glucose were hyperglycaemia associated with low levels of plasma insulin after two hours followed by hypoglycaemia associated with high levels of plasma insulin after six hours; subsequently hyperglycaemia progressively developed and this was associated with decreasing levels of plasma insulin. Further probing revealed that at two hours after streptozotocin injection, the pancreatic á-cells could not respond to an oral glucose load while, at six hours after, there was an apparent return of á-cell responsiveness, but subsequently á-cell responsiveness was progressively lost and histological examination revealed cellular damage. From these results, it is concluded that within six hours of injection, stretozotocin initiates pancreatic á-cell damage which leads to the development of diabetes mellitus. (AU)

Profile of experimental diabetes mellitus produced by streptozotocin in rats

There is an ongoing search for new and effective medications for treating diabetes mellitus. To facilitate this search, experimental diabetes induced by agents such as streptozotocin is often used. However, features of the diabetic state produced by streptozotocin need to be clarified in order to define the parameters within which investigators can work with the diabetic model. This study was therefore done to determine the profile produced by streptozotocin in rats. Single intraperitoneal doses of streptozotocin 40, 60, 80 mg/kg were administered to approximately 10 week-old Wistar rats of both sexes. Blood glucose and other parameters were observed for one year. Ames Gluco-System was used for glucose monitoring. Streptozotocin dose range 60-80 mg/kg was effective in precipitating a persistent diabetic state with onset within 24 hours. However, there was no persistent change in weight. There were indications that there may be variable production of insulin. There may also be some reversibility of the diabetic state in some animals. Overall the findings indicated that the severity and persistence of the diabetes produced depended on the dose of streptozotocin and that the dose range 60-80 mg/kg may be suitable to produce experimental diabetes for laboratory study(AU)

State of the art lecture: pharmacological intervention for the reduction of progression of diabetic nephropathy - abstract

Reduction of bloodpressure has been known, from the work of Parving et al (1987), to reduce the rate of decline of renal function in the nephropathy associated with Type-1 diabetes mellitus (IDDM), using conventional anti-hypertensive agents. More recently, interest in angiotensin-converting enzyme inhibitors (ACE-Is), and calcium channel blockers (CCBs) in the treatment of diabetic nephropathy, has been forthcoming. In diabetic nephropathy, induced in rats by streptozotocin, ACE-Is clearly alter renal haemodynamics and reduce proteinuria. Reduction of proteinuria is also seen in humans with diabetic nephropathy, and there is a suggestion of preservation of renal function, although no long-term studies have been published. Two studies are underway in non-hypertensive microalbuminuric subjects, but these have also not been published. The group of ACE-Is appears to have similar action in reducing proteinuria in diabetic nephropathy, but the same cannot be said for the CCBs. They differ in their action in reducing proteinuria, and dilitiazem may stand alone in reducing proteinuria in human diabetic nephropathy. Debate continues on the mechanism for reduction in proteinuria. Amelioration in systemic hypertension plays a role for all classes of antihypertensive drugs used, but the ACE-Is may alter glomerular permselectivity and thereby bring about reduction in proteinuria. Dietary reduction or protein intake may also play a protein preserving renal function as may reduction of lipids (AU)

Unstable diabetic state produced by a small dose of streptozotocin in rats

A diabetic state was induced with a single intraperitoneal dose (45 mg/kg) of streptozotocin in rats. Their fasting blood glucose concentrations oscillated between 12.7 ñ 1.9 mmol/l and 4.6 ñ 0.6 mmol/l during 35 days of monitoring. Their body weights were also reduced, while controls gained weight, although food consumption was not significantly different. Also, within the first «-hour of the oral glucose tolerance test, blood glucose concentration increased in the diabetic and the control rats, but only in the control rats was there a simultaneous increase in serus IRI concentration (7.2 ñ 8 x 10 to the 2nd power pmol/l to 27.0 ñ 5.2 x 10 to the 2nd power pmol/l) which, like the blood glucose concentration, subsequently fell to fasting level in the control rats. In the diabetic rats, however, it was not until the following hour of the tolerance test that serum IRI concentration increased (3.4 ñ 0.3 x 10 to the 2nd power pmol/l to 65.0 ñ 12.5 x 10 to the 2nd power pmol/l) and blood glucose concentration began to fall. By the end of the test in the diabetic rats, blood glucose concentration fell but remained significantly higher than the control value. Additionally, no pancreatic tumours were identified in these diabetic rats. The results therefore suggest that an unstable diabetic state was produced by streptozotocin because the treshold for insulin secretion by glucose was increased, while the production of insulin by the pancreas was not significantly affected (AU)