The weight-loss independent glycemic effects of gastric bypass (GB) are characterized by prandial short-lived hyperinsulinemia as a result of β-cell stimulation by glucose and incretins. To investigate the effect of parasympathetic nervous system (PNS) activity, a neural component of the enteroinsular axis, on islet function, 9 subjects with history of GB, 6 with prior sleeve gastrectomy (SG), and 4 non-surgical controls were recruited. The GB, SG, and CN groups were matched for BMI, FFM, A1C, and age; and the GB and SG for weight loss and time postsurgery; none had diabetes. To measure islet hormone responses to meal ingestion when the effect of GI hormones and glycemia is minimal, subjects consumed a liquid meal (280 kcal, 20% glucose) at 2 hr of a 5-hr hyperinsulinemic (120 mU/m2/min) hypoglycemic (55mg/dl) clamp with and without atropine infusion on two separate studies. Fasting levels of glucose, islet and gut hormones were similar among 3 groups and 2 studies. Despite similar insulin sensitivity among the groups the insulin clearance estimated before meal ingestion was larger in surgical patients (P=0.08). Suppression of endogenous β-cell secretion by hypoglycemia was less in both surgical groups compared to controls (P<0.001), but it was reduced by atropine in 3 groups (P<0.05). Hypoglycemia-induced glucagon secretion was not affected by PNS blockade. Blocking PNS diminished both β- and α-cell secretory response to meal ingestion (P < 0.05) in both surgical and non-surgical groups. Pre- and post-meal pancreatic polypeptide, marker of vagal input to the islet, declined to baseline values during atropine infusion. Meal-induced GIP secretion was similar in studies with and without atropine whereas blocking PNS significantly reduced GLP-1 secretion (P < 0.05) in all subjects. Our data shows that in nondiabetic subjects with prior GB and SG, PNS activity regulates islet and gut hormone secretory response to meal ingestion independent of glucose levels.
H. Honka: None. A.M. Al Zubaidi: None. R.A. DeFronzo: None. A. Gastaldelli: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Gilead Sciences, Inc., Inventiva Pharma, Novo Nordisk Inc. M. Salehi: None.
Finnish Cultural Foundation (00180071); National Institutes of Health (DK105379)