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OBJECTIVE Modern imaging techniques are detecting adrenal incidentalomas with increasing frequency. Recent data suggests food-dependent hypercortisolism in a subgroup of patients with bilateral macronodular hyperplasia due to aberrant adrenal responsiveness to gastric inhibitory polypeptide (GIP). We studied the putative influence of food intake on the hypothalamo–pituitary–adrenal (HPA) axis in patients with adrenal incidentalomas and possible mediation by GIP. PATIENTS AND MEASUREMENTS We examined 15 mildly obese patients with adrenal incidentalomas, eight healthy, lean subjects, and seven obese patients with the metabolic syndrome, who were matched for body weight and age. Each individual underwent oral glucose tolerance testing (OGTT, 75 g glucose), i.v. glucose administration (IVGTT, 30 g glucose over 1 h) and i.v. glucose plus GIP infusion (body weight adapted leading to physiological postprandial GIP serum levels) on three occasions. Plasma glucose, ACTH and cortisol were measured from blood samples taken every 15 minutes from time - 30 minutes to + 75 minutes. RESULTS OGTT, i.v. glucose administration and GIP infusion led to comparable glucose values within the groups. In contrast to normal subjects and patients with the metabolic syndrome, patients with adrenal incidentalomas had significantly higher mean cortisol values after oral glucose intake as compared to i.v. glucose administration or GIP infusion. The increase in cortisol levels was preceded by a corresponding ACTH increase. No significant effect of GIP administration on cortisol or on ACTH secretion could be detected. CONCLUSIONS Patients with adrenal incidentalomas showed an abnormal responsiveness of the pituitary–adrenal axis to oral glucose administration. The cortisol peaks in these patients seemed to be ACTH-mediated and were not induced by GIP. [ABSTRACT FROM AUTHOR]

The gut-born incretin hormone glucagon-like peptide-1 (GLP-1) delays gastric emptying. To elucidate the mechanisms by which GLP-1 affects gastroduodenal motility and glycaemia, we studied the effects of exendin(9–39), a potent GLP-1 receptor antagonist, on gastroduodenal motility and pancreatic hormones. In this randomized, double-blind, placebo-controlled, four-arm, cross-over trial, 10 healthy volunteers were studied during the interdigestive period followed by duodenal perfusion of a mixed liquid meal (250 kcal). On four separate days, exendin(9–39), atropine, exendin(9–39) + atropine or saline were infused intravenously. Antro-pyloro-duodenal and fundic motility were assessed. The compliance of the proximal stomach was determined by isobaric distensions. During fasting, exendin(9–39) did not influence proximal gastric volume, pyloric tone, and duodenal contractility. Exendin(9–39) significantly increased antral waves only in the absence of atropine. During duodenal meal perfusion, exendin(9–39) significantly reduced proximal gastric volume accommodation, abbreviated postprandial antral inhibition, reduced the postprandial increase in pyloric tone, and reduced gastric compliance. Atropine abolished the effects of exendin(9–39) on gastric volume accommodation but did not affect its effects on postprandial antroduodenal motility and on gastric compliance. Exendin(9–39) increased fasting and postprandial glycaemia and plasma glucagon but not insulin concentrations. Atropine did not affect GLP-1 secretion. Cholinergic mechanisms mediate the effects of GLP-1 on postprandial gastric accommodation but not on antro-pyloro-duodenal motility. GLP-1 reduces fasting and postprandial glycaemia, in part by reducing glucagon secretion. [ABSTRACT FROM AUTHOR]

Aim: To investigate the acute and longer-term effects of low (LGI) versus high glycaemic index (HGI) diets on hepatic fat and glycogen accumulation and related blood measures in healthy volunteers., Methods: Eight healthy men (age 20.1 ± 0.4 years, body mass index 23.0 ± 0.9 kg/m 2 ) attended a test day before and after a 7-day macronutrient- and energy-matched HGI or LGI diet, followed by a minimum 4-week wash-out period, and then returned to repeat the intervention with the alternative diet. During test days, participants consumed either an HGI or an LGI test meal corresponding to their diet week, and liver fat [ 1 H magnetic resonance spectroscopy (MRS)], glycogen ( 13 C MRS) and gastric content volume (MRI) were measured. Blood samples were obtained regularly throughout the test day to assess plasma glucose and insulin levels., Results: Plasma glucose and insulin peak values and area under the curve were significantly greater after the HGI test meal compared with the LGI test meal, as expected. Hepatic glycogen concentrations increased more after the HGI test meal ( P < .05) and peak levels were significantly greater after 7 days of HGI dietary intervention compared with those at the beginning of the intervention ( P < .05). Liver fat fractions increased significantly after the HGI dietary intervention compared with the LGI dietary intervention (two-way repeated-measures analysis of variance P ≤ .05)., Conclusions: Compared with an LGI diet, a 1-week HGI diet increased hepatic fat and glycogen stores. This may have important clinical relevance for dietary interventions in the prevention and management of non-alcoholic fatty liver disease., (© 2016 John Wiley & Sons Ltd.)

It is long known that both type 1 and type 2 diabetes can be associated with changes in gastric emptying; a number of publications have linked diabetes to delayed gastric emptying of variable severity and often with poor relationship to gastrointestinal symptomatology. In contrast, more recent studies have reported accelerated gastric emptying when adjusted for glucose concentration in patients with diabetes, indicating a reciprocal relationship between gastric emptying and ambient glucose concentrations. This review proposes that gastroparesis or gastroparesis diabeticorum, a severe condition characterized by a significant impairment of gastric emptying accompanied by severe nausea, vomiting, and malnutrition, is often overdiagnosed and not well contrasted with delays in gastric emptying. The article offers a clinically relevant definition of gastroparesis that should help differentiate this rare condition from (often asymptomatic) delays in gastric emptying. The fact that delayed gastric emptying can also be observed in non-diabetic individuals under experimental conditions in which hyperglycaemia is artificially induced suggests that a delay in gastric emptying rate when blood glucose concentrations are high is actually an appropriate physiological response to hyperglycaemia, slowing further increases in blood glucose. The article discusses the strengths and weaknesses of various methodologies for assessing gastric emptying, especially with respect to the diabetes population, and reviews newer diabetes therapies that decelerate the rate of gastric emptying. These therapies may be a beneficial tool in managing postprandial hyperglycaemia because they attenuate rapid surges in glucose concentrations by slowing the delivery of meal-derived glucose.

1. Gap junctions exist between circular muscle cells of the colon and between interstitial cells of Cajal (ICC) in the myenteric plexus of the gastrointestinal tract. They also probably couple intramuscular ICC with smooth muscle cells. Recent functional evidence for this was found in dye-coupling and myoelectrical experiments. 2. In the present study, we tested the hypothesis of gap junctions putatively being involved in neuromuscular interaction in mouse colon by using different classes of gap junction blockers. 3. Electrical field stimulation of the myenteric plexus elicited tetrodotoxin-sensitive and hexamethonium-independent fast and slow inhibitory junction potentials (fIJP and sIJP, respectively) in circular smooth muscle cells, as evaluated by intracellular recording techniques in impaled smooth muscle cells. Heptanol produced a time-dependent hyperpolarization of the membrane potential (MP) and abolished fIJP and sIJP. Octanol had no effect on the MP and abolished fIJP and sIJP. Carbenoxolone produced a time-dependent depolarization of the MP without any effect on fIJP or sIJP. The connexin 43 mimetic gap junction blocker GAP-27 had no effect on MP, fIJP or sIJP. 4. Based on the presently available gap junction blockers we found no evidence that gap junctions are involved in neuromuscular transmission in mouse colon, as suggested by morphological studies.

Background: This study was conducted to assess the efficacy of a novel 40-mg extended-release formulation of cisapride in reducing gastro-oesophageal reflux., Methods: According to a double-blind, randomized, placebo-controlled design, 19 patients with pathological gastro-oesophageal reflux were treated with extended (40 mg o.d.) or immediate (10 mg q.d.s.) release formulations for two periods of 4 days each (pH-monitoring on day four). Patients received identical treatments in both periods to allow limits of agreement defining equivalent potency of both formulations to be derived from intra-individual variability of treatment effects., Results: The extended-release formulation decreased total and upright reflux times by 5.5 +/- 1.3% and 8.1 +/- 2.1% (P < 0.001), respectively. It did not change the percentage supine reflux time but diminished the mean duration of reflux episodes by 1.0 +/- 0.4 min (P=0.005). The total number of reflux episodes remained unaltered with both formulations. Immediately-released cisapride decreased total, upright, and supine acid exposures by 5.8 +/- 1.3%, 6.8 +/- 1.6% (P < 0.002) and 3.6 +/- 1.8%, respectively, and mean duration of episodes by 0.9 +/- 0.2 min (P