Impaired insulin secretion and enhanced insulin sensitivity in cholecystokinin-deficient mice.

Published

Journal Article

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. RESEARCH DESIGN AND 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.

Full Text

Duke Authors

Cited Authors

  • Lo, C-M; Obici, S; Dong, HH; Haas, M; Lou, D; Kim, DH; Liu, M; D'Alessio, D; Woods, SC; Tso, P

Published Date

  • July 2011

Published In

Volume / Issue

  • 60 / 7

Start / End Page

  • 2000 - 2007

PubMed ID

  • 21602512

Pubmed Central ID

  • 21602512

Electronic International Standard Serial Number (EISSN)

  • 1939-327X

International Standard Serial Number (ISSN)

  • 0012-1797

Digital Object Identifier (DOI)

  • 10.2337/db10-0789

Language

  • eng