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

ABSTRACT: 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 ?-cells and an augmented incretin effect. An additional glucose-independent stimulation of insulin secretion in GB subjects was hypothesized.Fifteen subjects with prior GB, 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.The GB subjects had less suppression of fasting ?-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.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.

SUBMITTER: Salehi M

PROVIDER: S-EPMC4586360 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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

Salehi Marzieh M Woods Stephen C SC D'Alessio David A DA

Obesity (Silver Spring, Md.) 20150828 10

<h4>Objective</h4>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. An additional glucose-independent stimulation of insulin secretion in GB subjects was hypothesized.<h4>Methods</h4>Fifteen subjects with prior GB, six matched obese non surgical controls, and seven lean indiv ...[more]

PMID: 26316298

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Project description:Aims/hypothesisRoux-en-Y gastric bypass (RYGB) surgery is characterised by glycaemic variability. Prospective studies of glucose metabolism in pregnancy after RYGB are not available, therefore this study aimed to evaluate physiological alterations in glucose metabolism in pregnancy following RYGB.MethodsSixty-three pregnant women (25 who underwent RYGB, 19 non-operated obese control women and 19 normal weight control women) were included. Frequently sampled 3 h OGTTs and 1 h IVGTTs were performed between 24 and 28 weeks of gestation and, in a subgroup, were repeated at 3-6 months after delivery.ResultsWe observed major alterations in glucose kinetics during the OGTT, including an early increase in plasma glucose followed by hypoglycaemia in 90% of women who had previously undergone RYGB. The higher degree of glycaemic variability in this group was accompanied by increased insulin, C-peptide and glucagon concentrations after oral glucose load, whereas no differences in insulin response were observed after parenteral glucose administration (RYGB vs normal weight). IVGTT data suggested improved insulin sensitivity (mean difference 0.226 × 10-4 min-1 [pmol/l]-1 [95% CI 0.104, 0.348]; p < 0.001) and disposition index in pregnancies after RYGB when compared with obese control women. However, subtle alterations in insulin action and beta cell function were still observed when comparing women who had undergone RYGB with the normal-weight control group. Moreover, we observed that fetal growth was associated with maternal glucose nadir levels and insulin secretion in offspring of those who had previously undergone RYGB.Conclusions/interpretationPregnancies after RYGB are affected by altered postprandial glucose, insulin and C-peptide dynamics. Insulin sensitivity is improved by RYGB, although subtle alterations in beta cell function are observed. Longitudinal studies are needed to assess potential consequences for fetal development and pregnancy outcomes.

Dataset Information

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

Publications

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

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