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

Research output: Contribution to journalArticle

4 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.
LanguageEnglish
Pages190-199
JournalPancreas
Volume47
Issue number2
Early online date12 Jan 2018
DOIs
Publication statusE-pub ahead of print - 12 Jan 2018

Fingerprint

Gastrins
Islets of Langerhans
Cell Survival
Cholecystokinin
Peptides
Insulin
Streptozocin
Glucose
Cholecystokinin Receptors
Insulin-Secreting Cells
Glucagon
Membrane Potentials
Hydrocortisone
cholecystokinin 8
Rodentia
Cell Proliferation
Apoptosis
Cell Line
gastrin 17

Keywords

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

Cite this

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title = "Expression of Gastrin Family Peptides in Pancreatic Islets and Their Role in β-Cell Function and Survival",
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.",
keywords = "Beta-cell, alpha cells, islets, cholecystokinin, gastrin, diabetes",
author = "D Khan and Srividya Vasu and Charlotte Moffett and Nigel Irwin and Peter Flatt",
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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; Flatt, Peter.

In: Pancreas, Vol. 47, No. 2, 12.01.2018, p. 190-199.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Expression of Gastrin Family Peptides in Pancreatic Islets and Their Role in β-Cell Function and Survival

AU - Khan, D

AU - Vasu, Srividya

AU - Moffett, Charlotte

AU - Irwin, Nigel

AU - Flatt, Peter

PY - 2018/1/12

Y1 - 2018/1/12

N2 - 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.

AB - 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.

KW - Beta-cell

KW - alpha cells

KW - islets

KW - cholecystokinin

KW - gastrin

KW - diabetes

U2 - 10.1097/MPA.0000000000000983

DO - 10.1097/MPA.0000000000000983

M3 - Article

VL - 47

SP - 190

EP - 199

JO - Pancreas

T2 - Pancreas

JF - Pancreas

SN - 0885-3177

IS - 2

ER -