BROMOCRIPTINE SKF38393 AMELIORATES ISLET DYSFUNCTION IN THE DIABETIC (DB/DB) MOUSE/

Dysfunction of pancreatic islets plays a crucial role in the etiology of type II diabetes. Chronic hyperglycaemia or hyperlipidaemia may imp air islet function. Previous studies by our laboratory have demonstrat ed that dopaminergic agonists ameliorated hyperglycaemia and hyperlipi daemia in obese and diabetic rodents. In the present study, we investi gated the effect of a treatment with the dopamine D-2/D-1 receptor ago nists (bromocriptine/SKF38393, BC/SKF) on islet dysfunction in db/db m ice. Our results show that a 2-week BC/SKF treatment markedly reduced hyperglycaemia and hyperlipidaemia, and significantly improved islet d ysfunction demonstrated by an increase of secretagogue-stimulated insu lin release from islets of db/db mice to levels observed in islets fro m lean mice. There was also a fourfold increase of insulin content in the pancreas of BC/SKF-treated db/db mice compared with that in untrea ted controls. The effect of BC/SKF on islet function cannot be mimicke d in pair-fed animals. BC/SKF had no direct stimulatory effect on isle t insulin secretion, suggesting BC/SKF treatment improved islet functi on via an indirect mechanism. This treatment markedly improved the abn ormally elevated daily levels of corticosterone, blood glucose and pla sma lipids, supporting the view that BC/SKF may affect the neuroendocr ine system that in turn regulates peripheral metabolism and thereby im proves islet function.