Differential effect of endogenous glucagon-like peptide-1 on prandial glucose counterregulatory response to hypoglycaemia in humans with and without bariatric surgery.

Aim: To determine the effect of endogenous glucagon-like peptide 1 (GLP-1) on prandial counterregulatory response to hypoglycaemia after gastric bypass (GB).

Materials And Methods: Glucose fluxes, and islet-cell and gut hormone responses before and after mixed-meal ingestion, were compared during a hyperinsulinaemic-hypoglycaemic (~3.2 mmol/L) clamp with and without a GLP-1 receptor (GLP-1R) antagonist exendin-(9-39) infusion in non-diabetic patients who had previously undergone GB compared to matched participants who had previously undergone sleeve gastrectomy (SG) and non-surgical controls.

The effect of level of injury on diabetes incidence and mortality after spinal cord injury - a longitudinal cohort study.

Study Design: Retrospective longitudinal cohort study of veterans with SCI.

Objectives: Spinal cord injury (SCI) is associated with an increased risk of developing diabetes mellitus (DM), likely due to body composition alterations and autonomic nervous system dysfunction. These factors are more pronounced in persons with tetraplegia (TP) versus paraplegia (PP).

Vagal activation alters prandial bile acid composition and glycemia in patients with hypoglycemia after Roux-en-Y gastric bypass surgery.

Background: Altered prandial glycemic response after Roux-en-Y gastric bypass (RYGB) is exaggerated in patients with post-RYGB hypoglycemia. Increased contribution of glucagon-like peptide 1 (GLP-1) to prandial insulin secretion plays a key role in developing hypoglycemia after RYGB, but the role of nonhormonal gut factors remains unknown. Here, the effect of vagal activation on prandial bile acid (BA) composition in relation to glucose, insulin and gut hormone responses was examined in a small size group of nondiabetic subjects after RYGB with intact gallbladder compared to nonoperated controls.

Differential effect of gastric bypass versus sleeve gastrectomy on insulinotropic action of endogenous incretins.

Objective: Prandial hyperinsulinemia after Roux-en-Y gastric bypass surgery (GB), and to lesser degree after sleeve gastrectomy (SG), has been attributed to rapid glucose flux from the gut and increased insulinotropic gut hormones. However, β-cell sensitivity to exogenous incretin is reduced after GB. This study examines the effect of GB versus SG on prandial glycemia and β-cell response to increasing concentrations of endogenous incretins.

Altered Insulin Clearance after Gastric Bypass and Sleeve Gastrectomy in the Fasting and Prandial Conditions.

Background: The liver has the capacity to regulate glucose metabolism by altering the insulin clearance rate (ICR). The decreased fasting insulin concentrations and enhanced prandial hyperinsulinemia after Roux-en-Y gastric-bypass (GB) surgery and sleeve gastrectomy (SG) are well documented. Here, we investigated the effect of GB or SG on insulin kinetics in the fasting and fed states.

Prandial hepatic glucose production during hypoglycemia is altered after gastric bypass surgery and sleeve gastrectomy.

Aims/hypothesis: Roux-en Y gastric bypass surgery (GB) and sleeve gastrectomy (SG) alter prandial glucose metabolism, producing lower nadir glucose values and predisposing susceptible individuals to prandial hypoglycemia. The glycemic phenotype of GB or SG is associated with prandial hyperinsulinemia and hyperglucagonemia along with an increased influx of ingested glucose. Following insulin-induced hypoglycemia, glucagon is the most important stimulus for hepatic glucose production (HGP).

Characterization of glucose metabolism in youth with vs. without cystic fibrosis liver disease: A pilot study.

Background: Diabetes and liver disease are life-threatening complications of cystic fibrosis (CF). CF-liver disease is a risk factor for CF related diabetes (CFRD) development, but the underlying mechanisms linking the two co-morbidities are not known. The objective of this pilot study was to characterize glucose metabolism in youth with CF with and without liver disease.

Utility of Continuous Glucose Monitoring vs Meal Study in Detecting Hypoglycemia After Gastric Bypass.

Context: Gastric bypass (GB) increases postprandial glucose excursion, which in turn can predispose to the late complication of hypoglycemia. Diagnosis remains challenging and requires documentation of symptoms associated with low glucose and relief of symptom when glucose is normalized (Whipple triad).

Objective: To compare the yield of mixed meal test (MMT) and continuous glucose monitoring system (CGMS) in detecting hypoglycemia after GB.

Postprandial hypoglycemia after gastric bypass surgery: from pathogenesis to diagnosis and treatment.

Purpose Of Review: The Roux-en-Y gastric bypass surgery (RYGB) improves glucose control in majority of patients with type 2 diabetes. However, a minority group of individuals develop a life-threatening complication of hyperinsulinemic hypoglycemia. The goal of this review is to identify underlying mechanisms by which RYGB cause hypoglycemia and describe pathogenesis-driven strategies to diagnose and treat this condition.

Role of vagal activation in postprandial glucose metabolism after gastric bypass in individuals with and without hypoglycaemia.

Patients who have undergone gastric bypass surgery (GB) have enhanced postprandial hyperinsulinaemia and a greater incretin effect is apparent. In the present study, we sought to determine the effect of vagal activation, a neural component of the enteroinsular axis, on postprandial glucose metabolism in patients with and without hypoglycaemia after GB. Seven patients with documented post-GB hypoglycaemia, seven asymptomatic patients without hypoglycaemia post-GB, and 10 weight-matched non-surgical controls with normal glucose tolerance were recruited.

Beta-cell sensitivity to insulinotropic gut hormones is reduced after gastric bypass surgery.

Objective: Postprandial hyperinsulinaemia after Roux-en Y gastric bypass (GB) has been attributed to rapid nutrient flux from the gut, and an enhanced incretin effect. However, it is unclear whether surgery changes islet cell responsiveness to regulatory factors. This study tested the hypothesis that β-cell sensitivity to glucagon like-peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) is attenuated after GB.

The Role of Glucagon-Like Peptide-1 in Energy Homeostasis.

Energy homeostasis is coordinated by bidirectional communication pathways between the brain and peripheral organs, including adipose tissue, muscle, the pancreas, liver, and gut. Disruption of the integrated chemical, hormonal, and neuronal signals that constitute the gut-brain axis significantly contributes to disorders of metabolism and body weight. Initial studies of glucagon-like peptide-1 (GLP-1), a gut hormone released in response to the ingestion of nutrients, focused on its incretin actions to improve postprandial glucose homeostasis by enhancing meal-induced insulin secretion.

DNA Alkylating Agent Protects Against Spontaneous Hepatocellular Carcinoma Regardless of O6-Methylguanine-DNA Methyltransferase Status.

Hepatocellular carcinoma is increasingly important in the United States as the incidence rate rose over the last 30 years. C3HeB/FeJ mice serve as a unique model to study hepatocellular carcinoma tumorigenesis because they mimic human hepatocellular carcinoma with delayed onset, male gender bias, approximately 50% incidence, and susceptibility to tumorigenesis is mediated through multiple genetic loci. Because a human O(6)-methylguanine-DNA methyltransferase (hMGMT) transgene reduces spontaneous tumorigenesis in this model, we hypothesized that hMGMT would also protect from methylation-induced hepatocarcinogenesis.