Division of Diabetes, The University of Texas at San Antonio, San Antonio, TX.
Audie L. Murphy Memorial Veterans' Hospital, South Texas Veterans Health Care System, San Antonio, TX.
Diabetes. 2023 Oct 1;72(10):1374-1383. doi: 10.2337/db23-0207.
Roux-en-Y gastric bypass (GB) and sleeve gastrectomy (SG) surgeries increase prandial insulin and glucagon secretion but reduce the endogenous glucose production (EGP) response to hypoglycemia in comparison with control subjects who had not undergone gastric surgery (CN), suggesting that parasympathetic nervous system (PNS) plays a role. Here, we investigated the effect of acute PNS blockade on the post-meal counterregulatory response to insulin-induced hypoglycemia in GB and SG compared with CN. Glucose kinetics and islet cell secretion were measured in nine subjects without diabetes with GB and seven with SG and five CN during hyperinsulinemic-hypoglycemic clamp (∼3.2 mmol/L) combined with meal ingestion on two separate days with and without intravenous atropine infusion. Glucose and hormonal levels were similar at baseline and during steady-state hypoglycemia before meal ingestion in three groups and unaffected by atropine. Atropine infusion diminished prandial systemic appearance of ingested glucose (RaO) by 30%, EGP by 40%, and glucagon response to hypoglycemia by 90% in CN. In GB or SG, blocking PNS had no effect on the RaO or meal-induced hyperglucagonemia but increased EGP in SG without any effect in GB (P < 0.05 interaction). These findings indicate that cholinergic signal contributes to the recovery from hypoglycemia by meal consumption in humans. However, bariatric surgery dissipates PNS-mediated physiologic responses to hypoglycemia in the fed state.
Rerouted gut after Roux-en-Y gastric bypass (GB) and, to a lesser degree, after sleeve gastrectomy (SG) leads to larger glucose excursion and lower nadir glucose, predisposing individuals to hypoglycemia. Despite prandial hyperglucagonemia, endogenous glucose production response to hypoglycemia is reduced after GB or SG. Parasympathetic nervous system (PNS) activity plays a key role in regulation of glucose kinetics and islet cell function. We examined the effect of acute PNS blockade on counterregulatory glucose and islet cell response to meal ingestion during insulin-induced hypoglycemia among GB, SG, and control subjects who had not had gastric surgery. Our findings demonstrate that cholinergic signal is critical in the recovery from hypoglycemia by meal ingestion in humans who have not had gastric surgery, although prandial PNS-mediated physiologic responses to hypoglycemia are differentially changed by GB and SG.
研究急性副交感神经阻断对胃旁路术（GB）和袖状胃切除术（SG）与未行胃手术的对照受试者（CN）在胰岛素诱导低血糖期间餐后代偿性反应的影响。
在两次不同的日子里，在高胰岛素-低血糖钳夹（~3.2mmol/L）的同时，给 9 名无糖尿病的 GB 受试者和 7 名 SG 受试者以及 5 名 CN 受试者分别进食，测量他们的葡萄糖动力学和胰岛细胞分泌情况，在此期间，静脉内输注了阿托品。
在三组中，在餐前和稳态低血糖期间，葡萄糖和激素水平在基线时相似，并且不受阿托品影响。在 CN 中，阿托品输注使摄入葡萄糖的全身表现（RaO）减少 30%，使内源性葡萄糖生成（EGP）减少 40%，使低血糖时的胰高血糖素反应减少 90%。在 GB 或 SG 中，阻断副交感神经对 RaO 或餐引起的高血糖素血症没有影响，但增加了 SG 中的 EGP，而在 GB 中没有影响（P<0.05 交互作用）。
这些发现表明，在人类中，胆碱能信号通过进食来促进对低血糖的恢复。然而，减重手术后，在进食状态下，副交感神经介导的对低血糖的生理反应会被消除。
