Searchable abstracts of presentations at key conferences in endocrinology

ea0059p109 | Diabetes & cardiovascular | SFEBES2018

Activation of the adhesion GPCR GPR56 by a synthetic tethered agonist improvesislet β-cell function

Olaniru Oladapo Edward , Atanes Patricio , Persaud Shanta

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...

ea0077p177 | Metabolism, Obesity and Diabetes | SFEBES2021

Obesity-induced upregulation of chemokine Ccl4 in mouse visceral adipose tissue: effects on β-cell function

Ashik Tanyel , Atanes Patricio , Lee Vivian , Persaud Shanta

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...

ea0065p166 | Metabolism and Obesity | SFEBES2019

Obesity-induced changes in hepatocyte and skeletal myocyte expression of mRNAs encoding islet GPCR peptide ligands

Atanes Patricio , Smith Lorna , Bowe James , Persaud Shanta

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...

ea0065p234 | Metabolism and Obesity | SFEBES2019

Adhesion G-protein coupled receptors as novel players in islet development

Olaniru Oladapo Edward , Atanes Patricio , Toczyska Klaudia , Piao Xianhua , Persaud Shanta

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 ...

ea0028p178 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2012

Ablation of Peptide YY cells in adult mice reveals a role in beta-cell maintenance

Sam Amir , King Aileen , Hostomska Klara , Persaud Shanta , Liu Bo , Ghatei Mohammad , Bloom Stephen , Bewick Gavin

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...

ea0065p218 | Metabolism and Obesity | SFEBES2019

Inhibition of nicotinamide phosphoribosyltransferase (NAMPT) prevents cytokine-mediated beta cell dysfunction

Egbase Daniel , Sayers Sophie , Evans Elizabeth , Butterworth Sam , Greally Joshua , Bewick Gavin , Tsakmaki Anastasia , Persaud Shanta , Caton Paul

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...