Inhibitory effect of UDP-glucose on cAMP generation and insulin secretion.

Type-2 diabetes (T2D) is a global disease caused by the inability of pancreatic β-cells to secrete adequate insulin. However, the molecular mechanisms underlying the failure of β-cells to respond to glucose in T2D remains unknown. Here, we investigated the relative contribution of UDP-glucose (UDP-G), a P2Y14-specific agonist, in the regulation of insulin release using human isolated pancreatic islets and INS-1 cells.

CXCL14 Inhibits Insulin Secretion Independently of CXCR4 or CXCR7 Receptor Activation or cAMP Inhibition.

Background/aims: CXCL14, a secreted chemokine peptide that promotes obesity-induced insulin resistance, is expressed by islets, but its effects on islet function are unknown. The aim of this study was to determine the role of CXCL14 in β-cells and investigate how it transduces these effects.

Methods: Cxcl14 and Cxc-receptor mRNA expression was quantified by qPCR and CXCL14 expression in the pancreas was determined by immunohistochemistry.

Mesenchymal stromal cell secretory factors induce sustained improvements in islet function pre- and post-transplantation.

Background Aims: Mesenchymal stromal cells (MSCs) enhance islet function both in vitro and in vivo, at least in part by secreting ligands that activate islet G-protein coupled receptors (GPCRs). We assessed whether pre-treatment with a defined "cocktail" of MSC-secreted GPCR ligands enhances islet functional survival in vitro and improves the outcomes of islet transplantation in an experimental model of diabetes.

Methods: Isolated islets were cultured for 48 h with ANXA1, SDF-1 or C3a, alone or in combination.

Activation of imidazoline receptor I, and improved pancreatic β-cell function in human islets.

Aim: The impact of BL11282, an imidazoline receptor (NISCH) agonist, on potentiation of glucose-stimulated insulin secretion (GSIS) from isolated human non-diabetic (ND) and type 2 diabetic (T2D) islets was investigated.

Methods: Analysis of mRNA was performed by RNA-sequencing and qPCR. Insulin and cAMP by RIA and ELISA respectively.

Defining G protein-coupled receptor peptide ligand expressomes and signalomes in human and mouse islets.

Introduction: Islets synthesise and secrete numerous peptides, some of which are known to be important regulators of islet function and glucose homeostasis. In this study, we quantified mRNAs encoding all peptide ligands of islet G protein-coupled receptors (GPCRs) in isolated human and mouse islets and carried out in vitro islet hormone secretion studies to provide functional confirmation for the species-specific role of peptide YY (PYY) in mouse islets.

Materials And Methods: GPCR peptide ligand mRNAs in human and mouse islets were quantified by quantitative real-time PCR relative to the reference genes ACTB, GAPDH, PPIA, TBP and TFRC.