Proietto J, Rohner-Jeanrenaud F, Ionescu E, Jeanrenaud B
Laboratoires de Recherches Métaboliques, University of Geneva, Switzerland.
Metabolism. 1989 Apr;38(4):338-42. doi: 10.1016/0026-0495(89)90121-2.
When tested in insulin-deficient animal models of diabetes, islet activating protein (IAP) has been shown to increase the secretion of insulin and to improve glucose intolerance. The genetically obese fa/fa rat is an animal model of impaired oral glucose tolerance that does not have reduced insulin secretion. In this model IAP treatment increases basal insulin levels, resulting in lower basal glycemia. However, glucose tolerance following an oral glucose load was worsened by IAP. This was found to be due to an exaggerated stimulation of hepatic glucose production (HGP) following glucose, a defect that is already present in the absence of IAP. IAP has been reported to inhibit (by ADP ribosylation) the inhibitory regulatory protein (Ni) of adenylate cyclase. It is therefore suggested that the increased HGP following oral glucose in fa/fa rats either in the absence or in the presence of IAP treatment may result from a cAMP-mediated mechanism. A beta adrenergic activation or a stimulation of glucagon output could therefore be potential candidates responsible for glucose intolerance in obese fa/fa rats.
在胰岛素缺乏的糖尿病动物模型中进行测试时，胰岛激活蛋白（IAP）已被证明可增加胰岛素分泌并改善葡萄糖耐量。遗传性肥胖的fa/fa大鼠是口服葡萄糖耐量受损的动物模型，但其胰岛素分泌并未减少。在该模型中，IAP治疗可提高基础胰岛素水平，从而降低基础血糖水平。然而，口服葡萄糖负荷后的葡萄糖耐量因IAP而恶化。发现这是由于葡萄糖后肝脏葡萄糖生成（HGP）的过度刺激所致，这一缺陷在没有IAP的情况下就已存在。据报道，IAP可（通过ADP核糖基化）抑制腺苷酸环化酶的抑制性调节蛋白（Ni）。因此，有人认为，无论是否进行IAP治疗，fa/fa大鼠口服葡萄糖后HGP增加可能是由cAMP介导的机制引起的。因此，β肾上腺素能激活或胰高血糖素输出的刺激可能是导致肥胖fa/fa大鼠葡萄糖不耐受的潜在因素。
