title: Impaired insulin secretion and enhanced insulin sensitivity in cholecystokinin-deficient mice.
abstract: OBJECTIVE
  Cholecystokinin (CCK) is released in response to lipid intake and stimulates insulin secretion. We hypothesized that CCK deficiency would alter the regulation of insulin secretion and glucose homeostasis.
  
  
  METHODS
  We used quantitative magnetic resonance imaging to determine body composition and studied plasma glucose and insulin secretion of CCK gene knockout (CCK-KO) mice and their wild-type controls using intraperitoneal glucose and arginine infusions. The area of anti-insulin staining in pancreatic islets was measured by immunohistochemistry. Insulin sensitivity was assessed with euglycemic-hyperinsulemic clamps.
  
  
  RESULTS
  CCK-KO mice fed a low-fat diet had a reduced acute insulin response to glucose but a normal response to arginine and normal glucose tolerance, associated with a trend toward greater insulin sensitivity. However, when fed a high-fat diet (HFD) for 10 weeks, CCK-KO mice developed glucose intolerance despite increased insulin sensitivity that was associated with low insulin secretion in response to both glucose and arginine. The deficiency of insulin secretion in CCK-KO mice was not associated with changes in β-cell or islet size.
  
  
  CONCLUSIONS
  CCK is involved in regulating insulin secretion and glucose tolerance in mice eating an HFD. The impaired insulin response to intraperitoneal stimuli that do not typically elicit CCK release suggests that this hormone has chronic effects on β-cell adaptation to diet in addition to acute incretin actions.
authors: Cincinnati Obesity Research Center, Metabolic Diseases Institute, University of Cincinnati, Cincinnati, Ohio, USA.
authors: Chun-Min
authors: CM
authors: Lo
authors: Silvana
authors: S
authors: Obici
authors: H Henry
authors: HH
authors: Dong
authors: Michael
authors: M
authors: Haas
authors: Dawnwen
authors: D
authors: Lou
authors: Dae Hyun
authors: DH
authors: Kim
authors: Min
authors: M
authors: Liu
authors: David
authors: D
authors: D'Alessio
authors: Stephen C
authors: SC
authors: Woods
authors: Patrick
authors: P
authors: Tso
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