Abstract

Ghrelin, a 28-amino acid peptide, is a strong growth hormone secretagogue and a regulator of food intake. In addition, ghrelin is thought to play a role in insulin secretion and in glucose homeostasis. A lot of contradictory data have been reported in the literature regarding the co-localization of ghrelin with other hormones in the islet of Langerhans, its role in insulin secretion and attenuation of type 2 diabetes mellitus. In this study, we investigate the effect of chronic ghrelin treatment on glucose, body weight and insulin level in normal and streptozotocin-induced diabetic male Wistar rats. We have also examined the distribution pattern and co-localization of ghrelin with insulin in pancreatic islet cells using immunohistochemistry and immune-electron microscopy and the ability of ghrelin to stimulate insulin release from the CRL11065 beta cell line. Control, non-diabetic groups received intraperitoneal injection of normal saline, while treated groups received intraperitoneal injection of 5 µg/kg body weight of ghrelin (amino acid chain 24–51) on a daily basis for a duration of four weeks. Our results show that the administration of ghrelin increases the number of insulin-secreting beta cells and serum insulin level in both normal and diabetic rats. We also demonstrated that ghrelin co-localizes with insulin in pancreatic islet cells and that the pattern of ghrelin distribution is altered after the onset of diabetes. Moreover, ghrelin at a dose of 10−6 M and 10−12 M increased insulin release from the CRL11065 beta cell line. In summary, ghrelin co-localizes with insulin in the secretory granules of pancreatic beta cells and enhances insulin production.

Highlights

  • Ghrelin, a 28-amino acid peptide, was discovered in 1999 from a few milligram of stomach extract [1,2]

  • Ghrelin treatment did not significantly reduce fasting blood glucose (FBG) level in diabetic rats compared to untreated diabetic controls

  • In the pre-diabetic treated group, treating rats with ghrelin prior to the chemical induction of diabetes via STZ resulted in body weight increase, while the FBG was maintained within the normal range (Figure 1b)

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Summary

Introduction

A 28-amino acid peptide, was discovered in 1999 from a few milligram of stomach extract [1,2]. Ghrelin binds to ghrelin receptor or growth hormone secretagogue receptor (GHSR) which belongs to the G-Protein-coupled receptor family [6]. The GHSR gene generates GHS-R1a and GHS-R1b isoforms that differ in their carboxyl-terminal. Isoform 1a is known to be the active form where ghrelin binds and yields different signal transduction in different cells to exert its effect [7,8,9]. GHS-R was found to be expressed in the thyroid gland, spleen, myocardium and adrenal gland, stomach, small and large intestines, liver, lung, adipose tissue and pancreas, indicating the numerous roles of ghrelin [13,14]

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