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.

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BackgroundIn addition to motor impairments, personal changes and cognitive deficits, the inherited neurodegenerative disorder Huntington’s disease (HD) is complicated by peripheral pathology. The mutated huntingtin gene is ubiquitously expressed, and symptoms such as weight loss, skeletal muscle wasting, altered body composition and altered metabolism are present in HD. Muscle wasting is a well-recognised phenomenon in HD, which progresses with the disease and severely affects the prognosis and quality of life. The R6/2 mouse model of HD has previously been shown to exhibit progressive body weight loss, diabetes, skeletal muscle atrophy and altered body composition.Ghrelin, a neuropeptide produced in the stomach has been shown to have multi-tissue targets, and it has been suggested that the use of GHS-R1 agonists (Ghrelin and analogues) may be beneficial for many clinical problems such as muscle wasting, cancer cachexia, cognitive decline, diabetes and metabolic problems. AimIn this study we evaluate the effect of ghrelin on cachexia symptoms developed in the R6/2 mouse model of HD. MethodsWe treated mice with ghrelin and evaluated effects in circulation using antibody based assays and in target tissues using real-time PCR and western blot.ResultsWe can show that ghrelin administration postpones R6/2 mouse weight loss and normalises skeletal muscle catabolic gene expression profile. ConclusionFurther studies investigating GHS-R1 agonists for potential disease modifying effects in HD are warranted.This study was funded by an EHDN seed fund.