Endocrine Abstracts

GPR56 is an adhesion G-protein coupled receptor (GPCR), which we have shown to be the most abundant GPCR in mouse and human islets. The extracellular N-terminal domain of adhesion GPCRs contains a tethered agonist, buried within the GPCR autoproteolysis-inducing domain. Synthetic peptides mimicking tethered agonist sequences can activate a variety of adhesion GPCRs including GPR56. Here we investigated the effect of a GPR56 tethered agonist peptide, P7, on β-cell function...

Introduction: Adipose tissue-derived peptides, known as adipokines, act as key regulators of metabolic homeostasis, but little information is available on adipokine-mediated cross-talk with β-cells via islet GPCR interactions, nor whether this is altered in obesity. The expression profile of islet GPCR peptide ligand mRNAs in visceral adipose tissue from lean and diet-induced obese mice was therefore defined and the functional effects of Ccl4 on β-cells were characte...

Introduction: Insulin-sensitive tissues such as liver and skeletal muscle modify their gene expression under conditions of obesity-induced insulin resistance, and some of these gene products may be released to maintain glucose homeostasis. This study aimed to identify mRNAs encoding liver and skeletal muscle peptides that have the potential to regulate β-cell function by binding to islet GPCRs, and to quantify changes in expression of these liver and muscle mRNAs in obese...

Adhesion GPCRs (aGPCRs) have been implicated in developmental processes and deletion of some aGPCRs in neonatal mice results in decreased β-cell differentiation capacity, leading to glucose intolerance in adult life. Here, we investigated the expression of aGPCR mRNAs in mouse islets and determined the expression and function of GPR56, the most abundant aGPCR in islets, in developing mouse pancreas. Quantitative PCR indicated that mouse islets expressed mRNAs encoding 26 ...

In the pancreas, PYY is expressed in a subpopulation of non-beta cells in the islets of Langerhans. The role of PYY-expressing cells in the adult pancreas is unknown. We generated a mouse model in which administration of diphtheria toxin (DT) produced specific ablation of PYY-expressing cells in the colon, pancreas and brainstem. Interestingly, DT administration to adult mice resulted in severe hyperglycaemia associated with significant loss of pancreatic insulin and disrupted...

Intracellular nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme in the NAD salvage pathway. Abnormally elevated NAMPT can promote autoimmune and inflammatory processes. Many of these processes are key to type 1 diabetes (T1D) pathogenesis. Whilst NAMPT has been examined in other inflammatory diseases, the role of NAMPT in T1D remains unclear. To investigate the role of NAMPT in T1D, we used small molecule NAMPT modulators to determine the role of abnor...