Determining the insulin secretion potential for certain specific G-protein coupled receptors in MIN6 pancreatic beta cells

Hasan Gençoğlu,Peter M Jones,Kazim Şahi̇n

doi:10.3906/sag-1712-147

Abstract

Background/aimThe polypeptide hormone insulin is essential for the maintenance of whole-body fuel homeostasis, and defects in insulin secretion and/or action are associated with the development of type 1 and type 2 diabetes. The aim of this study was to assess the role of some G-protein coupled receptors (GPCRs), GPR54, GPR56, and GPR75, and cannabinoid receptors CB1R and CB2R, in the regulation of pancreatic β-cell function.Materials and methods Insulin secretion from mouse insulinoma β-cell line (MIN6) monolayers was assessed via insulin radioimmunoassay (RIA). Reverse transcription-polymerase chain reaction (RT-PCR) was used to assess the expression of some specific GPCRs and the other receptors by MIN6 pancreatic β-cells. Results The agonists were not found to be toxic for the MIN6 pancreatic β-cells within the range of the doses used in this study, whereas insulin secretion altered depending on the ligands and receptors. In addition, arachidonyl-2’-chloroethylamide (ACEA), carbachol, chemokine (C-C motif) ligand-5 (CCL5), and exendin as well as phorbol myristate acetate (PMA) ligands showed significant increases in the insulin secretion of MIN6 pancreatic β-cells.Conclusion Understanding the normal β-cell function and identifying the defects in β-cell function that lead to the development of diabetes will generate new therapeutic targets.

Highlights

Type 2 diabetes (T2DM) is characterized by a combination of peripheral insulin resistance and inadequate pancreatic β-cell insulin secretion
The agonists were not found to be toxic for the MIN6 pancreatic β-cells within the range of the doses used in this study, whereas insulin secretion altered depending on the ligands and receptors
Among the factors that reach the β-cell via the circulation, the incretin hormone glucagon-like peptide-1 (GLP-1) is of clinical relevance because it is a powerful enhancer of glucose-induced insulin secretion and has recently been introduced as a new therapy for T2DM [10]

Summary

Introduction

Type 2 diabetes (T2DM) is characterized by a combination of peripheral insulin resistance and inadequate pancreatic β-cell insulin secretion. MIN6 cells synthesize and secrete insulin, and they can be used either as adherent monolayers [8] or as three-dimensional isletlike structures (pseudoislets) [9]. Insulin secretion from pancreatic β-cells is regulated by both metabolic pathways (glucose, amino acids, nonesterified fatty acids) and nonnutrient extracellular signals (hormones, incretins, nonesterified fatty acids, neurotransmitters, and various small molecules) acting predominantly via G-protein coupled receptors (GPCRs) [8]. Among the factors that reach the β-cell via the circulation, the incretin hormone glucagon-like peptide-1 (GLP-1) is of clinical relevance because it is a powerful enhancer of glucose-induced insulin secretion and has recently been introduced as a new therapy for T2DM [10]

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