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Expression of Gastrin Family Peptides in Pancreatic Islets and Their Role in β-Cell Function and Survival

Khan, D, Vasu, Srividya, Moffett, Charlotte, Irwin, Nigel and Flatt, Peter (2018) Expression of Gastrin Family Peptides in Pancreatic Islets and Their Role in β-Cell Function and Survival. Pancreas, 47 (2). pp. 190-199. [Journal article]

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DOI: 10.1097/MPA.0000000000000983

Abstract

OBJECTIVES: Modulation of cholecystokinin (CCK) receptors has been shown to influence pancreatic endocrine function.METHODS: We assessed the impact of the CCKA and CCKB receptor modulators, (pGlu-Gln)-CCK-8 and gastrin-17, respectively, on β-cell secretory function, proliferation and apoptosis and glucose tolerance, and investigating alterations of CCK and gastrin islet expression in diabetes.RESULTS: Initially, the presence of CCK and gastrin, and expression of their receptors were evidenced in β-cell lines and mouse islets. (pGlu-Gln)-CCK-8 and gastrin-17 stimulated insulin secretion from BRIN-BD11 and 1.1B4 β-cells, associated with no effect on membrane potential or [Ca]i. Only (pGlu-Gln)-CCK-8 possessed insulin secretory actions in isolated islets. In agreement, (pGlu-Gln)-CCK-8 improved glucose disposal and glucose-induced insulin release in mice. In addition, (pGlu-Gln)-CCK-8 evoked clear satiety effects. Interestingly, islet colocalization of CCK with glucagon was elevated in streptozotocin- and hydrocortisone-induced diabetic mice, whereas gastrin coexpression in α cells was reduced. In contrast, gastrin colocalization within β-cells was higher in diabetic mice, while CCK coexpression with insulin was decreased in insulin-deficient mice. (pGlu-Gln)-CCK-8 and gastrin-17 also augmented human and rodent β-cell proliferation and offered protection against streptozotocin-induced β-cell cytotoxicity.CONCLUSIONS: We highlight the direct involvement of CCKA and CCKB receptors in pancreatic β-cell function and survival.

Item Type:Journal article
Keywords:Beta-cell; alpha cells; islets; cholecystokinin; gastrin; diabetes
Faculties and Schools:Faculty of Life and Health Sciences > School of Pharmacy and Pharmaceutical Science
Faculty of Life and Health Sciences > School of Biomedical Sciences
Faculty of Life and Health Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Pharmacy & Pharmaceutical Sciences
Biomedical Sciences Research Institute > Diabetes
ID Code:39363
Deposited By: Dr Nigel Irwin
Deposited On:23 Jan 2018 09:44
Last Modified:12 Jan 2019 23:23

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