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

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6 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)190-199
JournalPancreas
Volume47
Issue number2
Early online date12 Jan 2018
DOIs
Publication statusE-pub ahead of print - 12 Jan 2018

Keywords

  • Beta-cell
  • alpha cells
  • islets
  • cholecystokinin
  • gastrin
  • diabetes

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