Functional GIP receptors play a major role in islet compensatory response to high fat feeding in mice

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Abstract

BACKGROUND: Consumption of high fat diet and insulin resistance induce significant changes in pancreatic islet morphology and function essential for maintenance of normal glucose homeostasis. We have used incretin receptor null mice to evaluate the role of gastric inhibitory polypeptide (GIP) in this adaptive response.METHODS: C57BL/6 and GIPRKO mice were fed high fat diet for 45weeks from weaning. Changes of pancreatic islet morphology were assessed by immunohistochemistry. Body fat, glucose, insulin, glucagon, glucagon-like peptide 1 (GLP-1) and GIP were assessed by routine assays.RESULTS: Compared with normal diet controls, high fat fed C57BL/6 mice exhibited increased body fat, hyperinsulinaemia and insulin resistance, associated with decreased pancreatic glucagon, unchanged pancreatic GLP-1 and marked increases of insulin, islet number, islet size and both beta- and alpha-cell areas. Beta cell proliferation and apoptosis were increased under high fat feeding, but the overall effect favoured enhanced beta cell mass. A broadly similar pattern of change was observed in high fat fed GIPRKO mice but islet compensation was severely impaired in every respect. The inability to enhance beta cell proliferation was associated with the depletion of pancreatic GLP-1 and lack of hyperinsulinaemic response, resulting in non-fasting hyperglycaemia. GIP and GLP-1 were expressed in islets of all groups of mice but high fat fed GIPRKO mice displayed decreased numbers of GLP-1 containing alpha cells plus non-functional enhancement of pancreatic GIP content.GENERAL SIGNIFICANCE: These data suggest that GIP released from islet alpha-cells and intestinal K-cells plays an important role in islet adaptations to high fat feeding.
LanguageEnglish
Pages1206-1214
JournalBiochim Biophys Acta
Volume1850
Issue number6
DOIs
Publication statusPublished - 14 Feb 2015

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Gastric Inhibitory Polypeptide
Glucagon-Like Peptide 1
Fats
High Fat Diet
Islets of Langerhans
Glucagon
Insulin Resistance
Adipose Tissue
Cell Proliferation
Insulin
Incretins
Pancreatic Polypeptide
Glucose
Hyperinsulinism
Weaning
Inbred C57BL Mouse
Hyperglycemia
Homeostasis
Immunohistochemistry
Maintenance

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title = "Functional GIP receptors play a major role in islet compensatory response to high fat feeding in mice",
abstract = "BACKGROUND: Consumption of high fat diet and insulin resistance induce significant changes in pancreatic islet morphology and function essential for maintenance of normal glucose homeostasis. We have used incretin receptor null mice to evaluate the role of gastric inhibitory polypeptide (GIP) in this adaptive response.METHODS: C57BL/6 and GIPRKO mice were fed high fat diet for 45weeks from weaning. Changes of pancreatic islet morphology were assessed by immunohistochemistry. Body fat, glucose, insulin, glucagon, glucagon-like peptide 1 (GLP-1) and GIP were assessed by routine assays.RESULTS: Compared with normal diet controls, high fat fed C57BL/6 mice exhibited increased body fat, hyperinsulinaemia and insulin resistance, associated with decreased pancreatic glucagon, unchanged pancreatic GLP-1 and marked increases of insulin, islet number, islet size and both beta- and alpha-cell areas. Beta cell proliferation and apoptosis were increased under high fat feeding, but the overall effect favoured enhanced beta cell mass. A broadly similar pattern of change was observed in high fat fed GIPRKO mice but islet compensation was severely impaired in every respect. The inability to enhance beta cell proliferation was associated with the depletion of pancreatic GLP-1 and lack of hyperinsulinaemic response, resulting in non-fasting hyperglycaemia. GIP and GLP-1 were expressed in islets of all groups of mice but high fat fed GIPRKO mice displayed decreased numbers of GLP-1 containing alpha cells plus non-functional enhancement of pancreatic GIP content.GENERAL SIGNIFICANCE: These data suggest that GIP released from islet alpha-cells and intestinal K-cells plays an important role in islet adaptations to high fat feeding.",
author = "Charlotte Moffett and Srividya Vasu and Peter Flatt",
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Functional GIP receptors play a major role in islet compensatory response to high fat feeding in mice. / Moffett, Charlotte; Vasu, Srividya; Flatt, Peter.

Vol. 1850, No. 6, 14.02.2015, p. 1206-1214.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Functional GIP receptors play a major role in islet compensatory response to high fat feeding in mice

AU - Moffett, Charlotte

AU - Vasu, Srividya

AU - Flatt, Peter

PY - 2015/2/14

Y1 - 2015/2/14

N2 - BACKGROUND: Consumption of high fat diet and insulin resistance induce significant changes in pancreatic islet morphology and function essential for maintenance of normal glucose homeostasis. We have used incretin receptor null mice to evaluate the role of gastric inhibitory polypeptide (GIP) in this adaptive response.METHODS: C57BL/6 and GIPRKO mice were fed high fat diet for 45weeks from weaning. Changes of pancreatic islet morphology were assessed by immunohistochemistry. Body fat, glucose, insulin, glucagon, glucagon-like peptide 1 (GLP-1) and GIP were assessed by routine assays.RESULTS: Compared with normal diet controls, high fat fed C57BL/6 mice exhibited increased body fat, hyperinsulinaemia and insulin resistance, associated with decreased pancreatic glucagon, unchanged pancreatic GLP-1 and marked increases of insulin, islet number, islet size and both beta- and alpha-cell areas. Beta cell proliferation and apoptosis were increased under high fat feeding, but the overall effect favoured enhanced beta cell mass. A broadly similar pattern of change was observed in high fat fed GIPRKO mice but islet compensation was severely impaired in every respect. The inability to enhance beta cell proliferation was associated with the depletion of pancreatic GLP-1 and lack of hyperinsulinaemic response, resulting in non-fasting hyperglycaemia. GIP and GLP-1 were expressed in islets of all groups of mice but high fat fed GIPRKO mice displayed decreased numbers of GLP-1 containing alpha cells plus non-functional enhancement of pancreatic GIP content.GENERAL SIGNIFICANCE: These data suggest that GIP released from islet alpha-cells and intestinal K-cells plays an important role in islet adaptations to high fat feeding.

AB - BACKGROUND: Consumption of high fat diet and insulin resistance induce significant changes in pancreatic islet morphology and function essential for maintenance of normal glucose homeostasis. We have used incretin receptor null mice to evaluate the role of gastric inhibitory polypeptide (GIP) in this adaptive response.METHODS: C57BL/6 and GIPRKO mice were fed high fat diet for 45weeks from weaning. Changes of pancreatic islet morphology were assessed by immunohistochemistry. Body fat, glucose, insulin, glucagon, glucagon-like peptide 1 (GLP-1) and GIP were assessed by routine assays.RESULTS: Compared with normal diet controls, high fat fed C57BL/6 mice exhibited increased body fat, hyperinsulinaemia and insulin resistance, associated with decreased pancreatic glucagon, unchanged pancreatic GLP-1 and marked increases of insulin, islet number, islet size and both beta- and alpha-cell areas. Beta cell proliferation and apoptosis were increased under high fat feeding, but the overall effect favoured enhanced beta cell mass. A broadly similar pattern of change was observed in high fat fed GIPRKO mice but islet compensation was severely impaired in every respect. The inability to enhance beta cell proliferation was associated with the depletion of pancreatic GLP-1 and lack of hyperinsulinaemic response, resulting in non-fasting hyperglycaemia. GIP and GLP-1 were expressed in islets of all groups of mice but high fat fed GIPRKO mice displayed decreased numbers of GLP-1 containing alpha cells plus non-functional enhancement of pancreatic GIP content.GENERAL SIGNIFICANCE: These data suggest that GIP released from islet alpha-cells and intestinal K-cells plays an important role in islet adaptations to high fat feeding.

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