Ghrelin enhances glucose-induced insulin secretion in scheduled meal-fed sheep

Abstract

The purpose of this study was to investigate the effects of physiologic levels of ghrelin on insulin secretion and insulin sensitivity (glucose disposal) in scheduled fedsheep, using the hyperglycemic clamp and hyperinsulinemic euglycemic clamp respectively. Twelve castrated Suffolk rams (69·8 0·6 kg) were conditioned to be fed alfalfa hay cubes (2% of body weight) once a day. Three hours after the feeding, synthetic ovine ghrelin was intravenously administered to the animals at a rate of 0·025 and 0·05 µg/kg body weight (BW) per min for 3 h. Concomitantly, the hyperglycemic clamp or the hyperinsulinemic euglycemic clamp was carried out. In the hyperglycemic clamp, a target glucose concentration was clamped at 100 mg/100 ml above the initial level. In the hyperinsulinemic euglycemic clamp, insulin was intravenously administered to the animals for 3 h at a rate of 2 mU/kg BW per min. Basal glucose concentrations (44 1 mg/dl) were maintained by variably infusing 100 mg/dl glucose solution. In both clamps, plasma ghrelin concentrations were dose-dependently elevated and maintained at a constant level within the physiologic range. Ghrelin infusions induced a significant (ANOVA; P<0·01) increase in plasma GH concentrations. In the hyperglycemic clamp, plasma insulin levels were increased by glucose infusion and were significantly (P<0·05) greater in ghrelin-infused animals. In the hyperinsulinemic euglycemic clamp, glucose infusion rate, an index of insulin sensitivity, was not affected by ghrelin infusion. In conclusion, the present study has demonstrated for the first time that ghrelin enhances glucose-induced insulin secretion in the ruminant animal.

Influence of nutrient restriction and melatonin supplementation of pregnant ewes on maternal and fetal pancreatic digestive enzymes and insulin-containing clusters

“…This was not surprising as insulin is released in response to nutrient intake (Takahashi et al, 2006). Because these animals were not subjected to nutrient restriction they would have been secreting insulin at a higher rate to accommodate the rise in blood glucose and to promote protein synthesis.…”

Combined effect of salinomycin and feeding on whole body glucose kinetics in sheep fed a high-concentrate diet

“…In mice, ghrelin, which is released mainly from the oxyntic gland of the stomach with a transient surge just before feeding and stimulates GH secretion in rodents and ruminants [37], attenuates the capacity of insulin to suppress endogenous glucose production but reinforces that which stimulates glucose disposal, when it is infused for 3 h [38]. However, the steady-state glucose infusion rate was unaffected by ghrelin infusion in a hyperinsulinemic euglycemic clamp experiment in sheep [39]. It may be necessary to investigate whether a transient surge just before feeding in ghrelin produces a change in insulin sensitivity for glucose utilization rate in ruminants, in order to elucidate a mechanism for producing the feeding-induced increase in the rate.…”

Ghrelin differentially modulates glucose-induced insulin secretion according to feeding status in sheep

“…We observed that plasma levels of ghrelin were inversely related with those of insulin around feeding in sheep (unpublished data). Furthermore, we have demonstrated that ghrelin infusion stimulates glucose-induced insulin secretion in meal-fed sheep (Takahashi et al 2006). These observations led us to hypothesize that ghrelin regulates insulin secretion dependent on energy balance.…”

“…Insulin Insulin assay was done as described previously (Takahashi et al 2006). The insulin concentration was measured by competitive solid-phase immunoassay using Europium (Eu)-labeled synthetic bovine insulin and polystyrene microtiter strips (Nalge Nunc Int.)…”