Abstract
The gut hormones ghrelin, glucagon-like peptide 1 (GLP-1), and glucose-dependent insulinotropic peptide (GIP) have been intensively studied for their role in metabolism. It is, however, not well known whether the hormones interplay and regulate the secretion of each other. In this study, we studied the effect of ghrelin on GLP-1, GIP, and insulin secretion during an oral glucose tolerance test (OGTT) in mice. Intravenous administration of ghrelin caused increased GLP-1 secretion during the OGTT. On the other hand, ghrelin had no effect on circulating levels of glucose, insulin, and GIP. Furthermore, ghrelin treatment reduced proglucagon mRNA expression in GLUTag cells. The effect of ghrelin on GLP-1 secretion and proglucagon transcription was reinforced by the presence of GHS-R1a in human and mouse ileal L-cells, as well as in GLUTag cells. In summary, ghrelin is a regulator of GLP-1 secretion and transcription, and interfering with GHS-R1a signaling may be a way forward to enhance endogenous GLP-1 secretion in subjects with type 2 diabetes.
Highlights
The gastrointestinal tract harbors an array of hormones and regulatory peptides, involved in control of processes ranging from food intake to glucose homeostasis [1]
Our results suggest that intravenous administration of ghrelin increases glucagon-like peptide 1 (GLP-1) secretion during an oral glucose tolerance test (OGTT) and that ghrelin affects proglucagon transcription in vitro in GLUTag cells
Ghrelin had no effect on basal GLP-1 levels, but glucosestimulated GLP-1 secretion was found to be transiently increased in mice that had received intravenous administration of ghrelin (Figure 1A)
Summary
The gastrointestinal tract harbors an array of hormones and regulatory peptides, involved in control of processes ranging from food intake to glucose homeostasis [1]. GLP-1 is known to increase insulin secretion [2] and beta cell proliferation [3] and to inhibit intestinal motility [4], gastric emptying [5], and food intake [6]. Central and peripheral administration of ghrelin in rodents and humans has been shown to increase food intake [16,17,18] and to inhibit insulin secretion [19]. Ghrelin has been shown to inhibit insulin secretion in isolated mouse islets [20, 21] and in clonal beta cells [22, 23].
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