The ability of amylin to inhibit gastric emptying and glucagon secretion in rats is reduced under hypoglycemic conditions. These effects are considered part of a fail-safe mechanism that prevents amylin from further decreasing nutrient supply when blood glucose levels are low. Because these actions and amylin-induced satiation are mediated by the area postrema (AP), it is plausible that these phenomena are based on the co-sensitivity of AP neurons to amylin and glucose. Using hyperinsulinemic glucose clamps in unrestrained and freely-feeding rats, we investigated whether amylin's ability to inhibit food intake is also reduced by hypoglycemia (HYPO). Following an 18 h fast, rats were infused with insulin and glucose for 45 min to clamp blood glucose at baseline levels (between 90 and 100 mg/dL). HYPO (approximately 55 mg/dL) was induced between 45 and 60 min and then maintained for the remainder of the clamp. Rats were injected with amylin (20 µg/kg) or saline and offered normal chow at 85 min. Food intake was measured at 30 and 60 min after amylin. Control hyperinsulinemic/euglycemic (EU) rats were maintained at approximately 150 mg/dL (which is a physiological periprandial glucose level) before and after amylin injection. Terminal experiments tested the effect of amylin to induce the phosphorylation of ERK, a marker of amylin action in the AP, in EU and HYPO conditions. Amylin significantly reduced 30- and 60-min food intake in EU rats, but the effect at 60-min was attenuated in HYPO rats. Interestingly, glucose infusion rate had to be dramatically reduced at meal onset in saline-treated, but not in amylin-treated, EU or HYPO rats; this suggests that meal-related glucose appearance in the blood was inhibited by amylin under both EU and HYPO. Finally, amylin induced a similar pERK response in the AP in EU and HYPO rats. We conclude that amylin's action to decrease eating is blunted in hypoglycemia, and this effect seems to be downstream from amylin-induced pERK in AP neurons. These data allow us to extend the idea of a hypoglycemic brake on amylin's actions to its food intake-reducing effect, but also demonstrate that amylin can buffer meal-induced glucose appearance at EU and HYPO levels.

在低血糖条件下，胰岛淀粉样多肽抑制大鼠胃排空和胰高血糖素分泌的能力降低。这些效应被认为是故障安全机制的一部分，该机制可在血糖水平低时阻止胰岛淀粉样多肽进一步减少营养供应。由于这些作用和胰岛淀粉样多肽诱导的饱食感是由区域后区域（AP）介导的，因此这些现象似乎是基于AP神经元对胰岛淀粉样多肽和葡萄糖的共敏感性。在不受约束和自由喂养的大鼠中使用高胰岛素葡萄糖钳夹，我们调查了胰岛淀粉样多肽抑制食物摄入的能力是否也因低血糖症（HYPO）而降低。禁食18小时后，向大鼠注入胰岛素和葡萄糖45分钟，以将血糖钳制在基线水平（90至100 mg / dL之间）。在45至60分钟之间诱导产生HYPO（约55 mg / dL），然后在其余的钳夹中保持。给大鼠注射胰岛淀粉样多肽（20 µg / kg）或生理盐水，并在85分钟时提供正常食物。在胰岛淀粉样多肽注射后30和60分钟测量食物摄入量。在注射胰岛淀粉样多肽之前和之后，将对照高胰岛素/正常血糖（EU）大鼠维持在约150 mg / dL（这是生理上的外周葡萄糖水平）。最终实验测试了胰岛淀粉样多肽在EU和HYPO条件下诱导磷酸化ERK的作用，ERK是AP中胰岛淀粉样蛋白作用的标志。胰岛淀粉样多肽可显着减少EU大鼠30分钟和60分钟的食物摄取，但HYPO大鼠60分钟时的摄取减弱​​。有趣的是，在用盐水治疗的EU或HYPO大鼠中，在进餐时必须大幅度降低葡萄糖的输注速度，但在用胰岛淀粉样多肽治疗的EU或HYPO大鼠中则不能。这表明在EU和HYPO的作用下，胰岛淀粉样多肽抑制了血液中与膳食相关的葡萄糖出现。最后，胰岛淀粉样多肽在EU和HYPO大鼠的AP中诱导了类似的pERK反应。我们得出结论，在低血糖症中，胰岛淀粉样多肽减少饮食的作用减弱了，这种作用似乎在胰岛淀粉样多肽诱导的AP神经元中的pERK的下游。这些数据使我们能够将对胰岛淀粉样多肽作用的降血糖制动的概念扩展到其食物摄入减少效果，而且还证明了胰岛淀粉样多肽可以在EU和HYPO水平上抑制膳食诱导的葡萄糖出现。而且这种作用似乎在胰岛淀粉样多肽诱导的AP神经元中的pERK的下游。这些数据使我们能够将对胰岛淀粉样多肽作用的降血糖制动的概念扩展到其食物摄入减少效果，而且还证明了胰岛淀粉样多肽可以在EU和HYPO水平上抑制膳食诱导的葡萄糖出现。而且这种作用似乎在胰岛淀粉样多肽诱导的AP神经元中的pERK的下游。这些数据使我们能够将对胰岛淀粉样多肽作用的降血糖制动的概念扩展到其食物摄入减少效果，而且还证明了胰岛淀粉样多肽可以在EU和HYPO水平上抑制膳食诱导的葡萄糖出现。