Dataset Information

The human and mouse islet peptidome: effects of obesity and type 2 diabetes

ABSTRACT: To characterise the impact of metabolic disease on the peptidome of human and mouse pancreatic islets and the contribution of intra-islet glucagon-like peptide 1 (GLP-1) receptor signalling.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Pancreatic Islet, Pancreatic Delta Cell, Islet Of Langerhans, Pancreatic Islet Beta Cell, Pancreatic Alpha Cell

DISEASE(S): Type 2 Diabetes Mellitus

SUBMITTER: Richard Kay

LAB HEAD: Professor Fiona Gribble

PROVIDER: PXD026095 | Pride | 2021-08-24

REPOSITORIES: Pride

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Publications

The Human and Mouse Islet Peptidome: Effects of Obesity and Type 2 Diabetes, and Assessment of Intraislet Production of Glucagon-like Peptide-1.

Galvin Sam G SG Kay Richard G RG Foreman Rachel R Larraufie Pierre P Meek Claire L CL Biggs Emma E Ravn Peter P Jermutus Lutz L Reimann Frank F Gribble Fiona M FM

Journal of proteome research 20210823 9

To characterize the impact of metabolic disease on the peptidome of human and mouse pancreatic islets, LC-MS was used to analyze extracts of human and mouse islets, purified mouse alpha, beta, and delta cells, supernatants from mouse islet incubations, and plasma from patients with type 2 diabetes. Islets were obtained from healthy and type 2 diabetic human donors, and mice on chow or high fat diet. All major islet hormones were detected in lysed islets as well as numerous peptides from vesicula ...[more]

PMID: 34423991

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Project description:Expression of CD40 in non-hematopoietic cells has been linked to inflammation. We presented evidence that CD40, a T-cell costimulatory molecule, is expressed in human Î²-cells and the engagement of CD40 in insulinoma cells activated the NFKB and ERK1/2 pathways. CD40 activation in human islets cells induced secretion of IL-8, MCP-1 and MIP-1 Î², which is abrogated by inhibitors of NFkB and ERK1/2 inhibitors. In this study, we have studied gene expression mediated by CD40-CD40L interaction in islet cells. This approach identified 90 genes and transcripts exhibiting at least a 1.7 fold increase in their expression intensity after treatment with soluble CD40L. A significant number of genes were related to inflammation and oxidative stress. We have a strong overexpression of CXCL1 (GroÎ±), CXCL2 (Mif2) and CXCL3; chemokines belonging to CXC family structurally related to Il-8. 11 genes were selected from this group and further quantified by Real Time PCR, including CXCL1. Activation of islet cells with CD40L induced the secretion of CXCL1 in a NFKB dependent manner. Engagement of CD40 in islet cells did not induce apoptosis, neither Î²-cell death and did not enhanced TNF-Î± mediated cell death as observed in insulinoma cells. CD40 activation in insulinoma cells, results in ERK1/2 dependent phsophorylation of synapsin I, a protein associated with the exocytosis machinery in neurons and Î²-cells. However, treatment of islets with soluble CD40L did not affect glucose induced insulin secretion. It has been reported that ductal cells always present in human islet preparations express CD40 constitutively (ref). We found that CD40-CD40L interaction in ductal cells, unlike in Î²-cells, induces secretion of diabetogenic cytokines IFNÎ³ and TNF-Î±. Furthermore, incubation of islets containing ductal cells with CD40L decreased Î²-cells viability as assessed by measurement of their mitochondrial membrane potential Experiment Overall Design: We isolated islet cells from three patients. Part of islet cells from each patient has been treated with CD40L. We compared gene expression in treated cells vs untreated for each patient using dye-swap.

Dataset Information

The human and mouse islet peptidome: effects of obesity and type 2 diabetes

Publications

The Human and Mouse Islet Peptidome: Effects of Obesity and Type 2 Diabetes, and Assessment of Intraislet Production of Glucagon-like Peptide-1.

Similar Datasets

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