Date of Award

5-2015

Document Type

Thesis

Degree Name

Master of Science in Medical Sciences (MSMS)

Department

Medical Education

First Advisor

Emest Adeghate

Second Advisor

Abdu Adem

Third Advisor

Frank C. Howarth

Abstract

Ghrelin, a 28-amino acid peptide, is identified as the endogenous ligand of the orphan growth hormone secretagogue-receptor type la. Ghrelin presents a unique modification at Ser3 position essential for its activity. It was first discovered in the stomach of rat in 1999. Aside from ghrelin’s role as a potent growth hormone secretagogue and food intake modulator, ghrelin is thought to play a role in insulin and glucagon secretion and in glucose homeostasis. A lot of contradictory data have been reported in the literature regarding ghrelins co-localization with other hormones in the islets of Langerhans, its role in insulin secretion and attenuation of type 2 diabetes mellitus. In this study, we investigated the effect of chronic ghrelin treatment on glucose, body weight and insulin level in normal, STZ-induced diabetic and ghrelin-treated male Wistar rats. We also examined the distribution pattern and co-localization of ghrelin in the pancreatic islet of Langerhans with both pancreatic hormones; insulin and glucagon. In addition, we examined how ghrelin treatment influences liver function in normal and STZ-diabetic Wistar rats. Control groups received intraperitoneal injection of normal saline while treated groups received intraperitoneal injections of 5μg/kg ghrelin on daily basis for duration of four weeks. Our results show that administration of ghrelin increases the serum insulin level in both normal and diabetic rats. We also demonstrated that ghrelin co-localizes with insulin as well as glucagon in the pancreatic islet cells and that the pattern of ghrelin distribution is shown to alter after the onset of diabetes. Moreover, ghrelin treatment increased insulin secretion as a result of increasing insulin-secreting β cells. In conclusion ghrelin co-localizes with both insulin and glucagon in pancreatic islet cells and plays a regulatory role in insulin secretion.

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