Gastric bypass alters both glucose-dependent and glucose-independent regulation of islet hormone secretion

AIMS: Roux-en-Y gastric bypass surgery (GB) is characterized by accentuated, but short-lived postprandial elevations of blood glucose and insulin. This profile has been attributed to effects of relative hyperglycemia to directly stimulate β-cells and an augmented incretin effect. We hypothesized additional glucose-independent stimulation of insulin secretion in GB subjects. METHODS: Fifteen subjects with prior GB, and six matched obese non-surgical controls, and seven lean individuals were recruited. Islet hormones were measured before and after meal ingestion during hyperinsulinemic hypoglycemic clamps to minimize the direct effects of glycemia and glucose-dependent gastrointestinal hormones on insulin secretion. RESULTS: The GB subjects had less suppression of fasting β-cell secretion during the insulin clamp compared to controls. In addition, meal-induced insulin secretion increased in the GB subjects but not controls during fixed sub-basal glycemia. In contrast the glucagon responses to hypoglycemia and meal ingestion were lower in the GB subjects than controls. CONCLUSIONS: Among subjects with GB the response of insulin and glucagon secretion to decreasing blood glucose is blunted, but meal-induced insulin secretion is stimulated even at fixed systemic sub-basal glycemia. These findings indicate that following GB islet hormone secretion is altered as a result of factors beyond circulatory glucose levels.