Effects of aminoguanidine on rat pancreatic islets in culture and on the pancreatic islet blood flow of anaesthetized rats.
Aminoguanidine (AG; < or =0.5 mM) is a potent inhibitor of the inducible form of nitric oxide synthase (iNOS) and, at higher concentrations, is also able to prevent advanced glycosylation of proteins. Due to these properties, AG might be an interesting therapeutic compound for prevention of the development of diabetes and for prevention of diabetes complications. In the present study, we examined the effect of AG (0.1, 0.5, 1.0, 5.0, or 10 mM) on prolonged in vitro culture of isolated rat pancreatic islets. Furthermore, the acute effect of AG on pancreatic and islet blood flow in anaesthetized rats was studied with a microsphere technique. Culture for 6 days of pancreatic islets at either 11.1 mM or 28 mM glucose, in the presence of 0.1-1.0 mM AG, was not toxic to the islet cells or impaired insulin secretion. However, when islets were cultured for 8 days with the addition of 5 mM AG at 11.1 mM or 28 mM glucose, a 50% inhibition of glucose-stimulated insulin release was observed. Rats injected intravenously with AG (1, 10, or 50 mg/kg body weight) had a decreased pancreatic blood flow 30 min later. Glucose injection (1 g/kg body weight) increased the islet blood flow, and this effect was not attenuated by AG. The present data suggest that AG, when used in concentrations that inhibit iNOS, can affect pancreatic blood flow, but appears not to be directly harmful to beta-cell function.
Holstad
M
M
Department of Medical Cell Biology, Uppsala University, Sweden.
Jansson
L
L
Sandler
S
S
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects*; D002478:Cells, Cultured / Q000187:drug effects; D004247:DNA / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D010179:Pancreas / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D006146:Guanidines; D007328:Insulin; D004247:DNA; C004479:pimagedine