Ammon H P
Department of Pharmacology, University of Tübingen.
Exp Clin Endocrinol Diabetes. 1997;105 Suppl 2:43-7. doi: 10.1055/s-0029-1211796.
Type-2 diabetes frequently is the consequence of overnutrition causing overweight, which then produces insulin resistance. The following hyperglycemia induces permanent overstimulation of the insulin secretory machinery of the B-cell, which results in hyperinsulinemia and/or hypoinsulinemia. The mechanisms, however, of these disturbances are not understood so far. Animal models, which can be used to solve these questions, are, among others, long-term incubation of pancreatic islets in culture in the presence of high glucose and/or long-term infusion of rats with glucose. Using these models sensitization [Bedoya and Jeanrenaud, 1991; Leahy et al., 1987; Purrello et al., 1992; Thams, 1991; Thibault et al., 1993; Timmers et al., 1990] and/or desensitization of insulin release [Bedoya and Jeanrenaud, 1991; Leahy et al., 1987; Davalli et al., 1992; Eizirik et al., 1992; Bolaffi et al., 1988; Timmers et al., 1990] have been reported. Whether or not there is sensitization or desensitization depends on the glucose concentration [Eizirik et al., 1992; Leahy et al., 1986; Sako and Grill, 1990] and the duration of glucose action [Bedoya and Jeanrenaud, 1991; Bolaffi et al., 1988]. Both, sensitization and desensitization, appear to be reversible on return to normal glucose or mild hypoglycemia [Leahy and Weir, 1991; Svenson and Hellerström, 1991]. It seems, however, that there is a fluent change from the first occurring hyperinsulinemia to hypoinsulinemia. In this lecture I first want to talk about the possible mechanism of sensitization of insulin secretion discussing previous results we have obtained from rat islets isolated after a 48 hours period of i.v. infusion with 50% glucose. In the second part I will discuss some of the findings coming from the respective literature concerning desensitization of insulin secretion.
2型糖尿病常常是营养过剩导致超重的结果，而超重进而会产生胰岛素抵抗。随后出现的高血糖会导致胰岛B细胞的胰岛素分泌机制持续受到过度刺激，从而引发高胰岛素血症和/或低胰岛素血症。然而，目前对这些紊乱的机制尚不清楚。可用于解决这些问题的动物模型包括在高葡萄糖存在的情况下对胰岛进行长期体外培养，以及对大鼠进行长期葡萄糖输注等。利用这些模型，已经有关于胰岛素释放致敏[贝多亚和让雷诺，1991年；利ahy等人，1987年；普雷雷洛等人，1992年；塔姆斯，1991年；蒂博等人，1993年；廷默斯等人，1990年]和/或脱敏[贝多亚和让雷诺，1991年；利ahy等人，1987年；达瓦利等人，1992年；艾齐里克等人，1992年；博拉菲等人，1988年；廷默斯等人，1990年]的报道。是否存在致敏或脱敏取决于葡萄糖浓度[艾齐里克等人，1992年；利ahy等人，1986年；酒井和格里尔，1990年]以及葡萄糖作用的持续时间[贝多亚和让雷诺，1991年；博拉菲等人，1988年]。致敏和脱敏在恢复到正常血糖或轻度低血糖时似乎都是可逆的[利ahy和韦尔，1991年；斯文森和赫勒斯特伦，1991年]。然而，从最初出现的高胰岛素血症到低胰岛素血症似乎存在一个连续的变化过程。在本次讲座中，我首先想探讨胰岛素分泌致敏的可能机制，讨论我们此前从静脉输注50%葡萄糖48小时后分离的大鼠胰岛中获得的结果。在第二部分，我将讨论来自相关文献中关于胰岛素分泌脱敏的一些研究发现。
