Effects of Ghrelin on the Insulin and Glycemic Responses to Glucose, Arginine, or Free Fatty Acids Load in Humans

Abstract

Ghrelin possesses central and peripheral endocrine actions including influence on the endocrine pancreatic function. To clarify this latter ghrelin action, in seven normal young subjects [age (mean +/- SEM), 28.3 +/- 3.1 yr; body mass index, 21.9 +/- 0.9 kg/m(2)), we studied insulin and glucose levels after acute ghrelin administration (1.0 microg/kg i.v.) alone or combined with glucose [oral glucose tolerance test (OGTT), 100 g orally], arginine (ARG, 0.5 g/kg i.v.) or free fatty acid (FFA, Intralipid 10%, 250 ml). Ghrelin inhibited (P < 0.05) insulin and increased (P < 0.05) glucose levels. OGTT increased (P < 0.01) glucose and insulin levels. FFA increased (P < 0.05) glucose but did not modify insulin levels. ARG increased (P < 0.05) both insulin and glucose levels. Ghrelin did not modify both glucose and insulin responses to OGTT as well as the FFA-induced increase in glucose levels; however, ghrelin administration was followed by transient insulin decrease also during FFA. Ghrelin blunted (P < 0.05) the insulin response to ARG and enhanced (P < 0.05) the ARG-induced increase in glucose levels. In all, ghrelin induces transient decrease of spontaneous insulin secretion and selectively blunts the insulin response to ARG but not to oral glucose load. On the other hand, ghrelin raises basal glucose levels and enhances the hyperglycemic effect of ARG but not that of OGTT. These findings support the hypothesis that ghrelin exerts modulatory action of insulin secretion and glucose metabolism in humans.

Ghrelin, des-acyl ghrelin and obestatin: Three pieces of the same puzzle

“…On the basis of a C-terminal Gly-Lys motif, amidation of obestatin was assumed and verified as a prerequisite for biological activity [162]. Furthermore, the mass spectrometric data indicated that this peptide may be processed to a 13 amino acid peptide, obestatin (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). Further information is required to establish exactly how obestatin (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23) is formed, although, a recent study indicates that this isoform is indeed biologically active [62].…”

“…Recently, it was demonstrated that ghrelin can inhibit the activity of the glucosensing neurons (glucose-inhibited and glucose-excited neurons) in the dorsal vagal complex of rats [118,152]. Depending upon the experimental condition, ghrelin has been reported to be able to either inhibit or stimulate insulin secretion in animals and humans [14]. Nevertheless, most available data suggest a negative association between systemic ghrelin and insulin levels, with ghrelin inhibiting insulin secretion both in vitro and in most human or animal studies [14].…”

Ghrelin prevents development of diabetes at adult age in streptozotocin-treated newborn rats

“…Ghrelin may have direct biological action within the pancreas, potentially functioning during pancreatic development. Although these results remain controversial, in vivo peripheral administration of ghrelin modulated plasma insulin and glucose levels [4][5][6][7]. The growth hormone secretagogue receptor (GHS-R), for which ghrelin can serve as a ligand, is expressed in the pancreas [8,9].…”

Obesity vaccines

“…Ghrelin was also shown to mediate diabetic hyperphagia 42 and to regulate glucose homeostasis by direct action in the pancreas, being able to supress insulin secretion in vitro and increase glucose in vivo, 43,44 while insulin reduces ghrelin levels suggesting the existence of an inverse relationship between the two hormones. 45 In addition, bariatric surgery has been demonstrated to interfere with appetite regulating pathways, inducing changes in gastro-intestinal hormones levels that could contribute to weight loss, in particular by suppressing the rise in ghrelin levels that is normally observed after caloric deprivation.…”