Department of Internal Medicine, Center for Hypothalamic Research, UT Southwestern Medical Center, Dallas, TX, United States.
Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX, United States.
Front Endocrinol (Lausanne). 2020 Sep 11;11:606. doi: 10.3389/fendo.2020.00606. eCollection 2020.
Insulin-induced hypoglycemia is a major limiting factor in maintaining optimal blood glucose in patients with type 1 diabetes and advanced type 2 diabetes. Luckily, a counterregulatory response (1) system exists to help minimize and reverse hypoglycemia, although more studies are needed to better characterize its components. Recently, we showed that the hormone ghrelin is permissive for the normal CRR to insulin-induced hypoglycemia when assessed in mice without diabetes. Here, we tested the hypothesis that ghrelin also is protective against insulin-induced hypoglycemia in the streptozotocin (2) mouse model of type 1 diabetes. STZ-treated ghrelin-knockout (KO) (3) mice as well as STZ-treated wild-type (WT) littermates were subjected to a low-dose hyperinsulinemic-hypoglycemic clamp procedure. The STZ-treated ghrelin-KO mice required a much higher glucose infusion rate than the STZ-treated WT mice. Also, the STZ-treated ghrelin-KO mice exhibited attenuated plasma epinephrine and norepinephrine responses to the insulin-induced hypoglycemia. Taken together, our data suggest that without ghrelin, STZ-treated mice modeling type 1 diabetes are unable to mount the usual CRR to insulin-induced hypoglycemia.
胰岛素诱导的低血糖是 1 型糖尿病和 2 型糖尿病晚期患者维持最佳血糖的主要限制因素。幸运的是，存在一种代偿性反应 (1) 系统来帮助最小化和逆转低血糖，尽管需要更多的研究来更好地描述其成分。最近，我们表明，在没有糖尿病的小鼠中评估时，激素 ghrelin 允许对胰岛素诱导的低血糖进行正常的 CRR。在这里，我们测试了这样一个假设，即 ghrelin 也可以防止链脲佐菌素 (2) 1 型糖尿病小鼠模型中的胰岛素诱导的低血糖。STZ 处理的 ghrelin 敲除 (KO) (3) 小鼠以及 STZ 处理的野生型 (WT) 同窝仔鼠接受了低剂量高胰岛素-低血糖钳夹程序。与 STZ 处理的 WT 同窝仔鼠相比，STZ 处理的 ghrelin-KO 小鼠需要更高的葡萄糖输注率。此外，STZ 处理的 ghrelin-KO 小鼠对胰岛素诱导的低血糖的血浆肾上腺素和去甲肾上腺素反应减弱。总之，我们的数据表明，没有 ghrelin，模拟 1 型糖尿病的 STZ 处理小鼠无法对胰岛素诱导的低血糖产生通常的 CRR。
