Liang Y, Jetton T L, Lubkin M, Meier A H, Cincotta A H
Ergoscience, Charlestown, Massachusetts 02129, USA.
Cell Mol Life Sci. 1998 Jul;54(7):703-11. doi: 10.1007/s000180050197.
Dysfunction of pancreatic islets plays a crucial role in the etiology of type II diabetes. Chronic hyperglycaemia or hyperlipidaemia may impair islet function. Previous studies by our laboratory have demonstrated that dopaminergic agonists ameliorated hyperglycaemia and hyperlipidaemia in obese and diabetic rodents. In the present study, we investigated the effect of a treatment with the dopamine D2/D1 receptor agonists (bromocriptine/SKF38393, BC/SKF) on islet dysfunction in db/db mice. Our results show that a 2-week BC/SKF treatment markedly reduced hyperglycaemia and hyperlipidaemia, and significantly improved islet dysfunction demonstrated by an increase of secretagogue-stimulated insulin release from islets of db/db mice to levels observed in islets from 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 untreated controls. The effect of BC/SKF on islet function cannot be mimicked in pair-fed animals. BC/SKF had no direct stimulatory effect on islet insulin secretion, suggesting BC/SKF treatment improved islet function via an indirect mechanism. This treatment markedly improved the abnormally elevated daily levels of corticosterone, blood glucose and plasma lipids, supporting the view that BC/SKF may affect the neuroendocrine system that in turn regulates peripheral metabolism and thereby improves islet function.
胰岛功能障碍在II型糖尿病的病因中起关键作用。慢性高血糖或高血脂可能损害胰岛功能。我们实验室之前的研究表明，多巴胺能激动剂可改善肥胖和糖尿病啮齿动物的高血糖和高血脂。在本研究中，我们调查了用多巴胺D2/D1受体激动剂（溴隐亭/SKF38393，BC/SKF）治疗对db/db小鼠胰岛功能障碍的影响。我们的结果表明，为期2周的BC/SKF治疗显著降低了高血糖和高血脂，并显著改善了胰岛功能障碍，表现为促分泌剂刺激的db/db小鼠胰岛胰岛素释放增加至瘦小鼠胰岛中观察到的水平。与未治疗的对照组相比，BC/SKF治疗的db/db小鼠胰腺中的胰岛素含量也增加了四倍。在配对喂养的动物中无法模拟BC/SKF对胰岛功能的影响。BC/SKF对胰岛胰岛素分泌没有直接刺激作用，表明BC/SKF治疗通过间接机制改善了胰岛功能。这种治疗显著改善了皮质酮、血糖和血浆脂质每日异常升高的水平，支持了BC/SKF可能影响神经内分泌系统，进而调节外周代谢从而改善胰岛功能的观点。
