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 45 weeks 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.
  
  
  CONCLUSIONS
  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.
authors: SAAD Centre for Pharmacy and Diabetes, University of Ulster, Cromore Road, Coleraine BT52 1SA, Northern Ireland, UK. Electronic address: s.vasu@ulster.ac.uk.
authors: R Charlotte
authors: RC
authors: Moffett
authors: SAAD Centre for Pharmacy and Diabetes, University of Ulster, Cromore Road, Coleraine BT52 1SA, Northern Ireland, UK.
authors: Srividya
authors: S
authors: Vasu
authors: SAAD Centre for Pharmacy and Diabetes, University of Ulster, Cromore Road, Coleraine BT52 1SA, Northern Ireland, UK.
authors: Peter R
authors: PR
authors: Flatt
mesh_terms: D000222:Adaptation, Physiological; D050154:Adiposity; D000818:Animals; D017209:Apoptosis; D001786:Blood Glucose / Q000378:metabolism; D049109:Cell Proliferation; D059305:Diet, High-Fat; D005749:Gastric Inhibitory Polypeptide / Q000097:blood*; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007413:Intestinal Mucosa / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011964:Receptors, Gastrointestinal Hormone / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D007328:Insulin; D011964:Receptors, Gastrointestinal Hormone; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; C041086:gastric inhibitory polypeptide receptor
keywords: Alpha-cell; Gastric inhibitory polypeptide; Immunohistochemistry; K-cell