Effects of lactogen resistance and GH deficiency on mouse metabolism: pancreatic hormones, adipocytokines, and expression of adiponectin and insulin receptors.
Journal Article (Journal Article)
We recently described a novel mouse model that combines resistance to lactogenic hormones with GH deficiency (GHD). The GHD/lactogen-resistant males develop obesity and insulin resistance with age. We hypothesized that altered production of pancreatic hormones and dysregulation of adipocytokine secretion and action contribute to the pathogenesis of their insulin resistance. Double-mutant males (age 12-16 months) had fasting hyperinsulinemia, hyperamylinemia, hyperleptinemia, and a decreased ratio of adiponectin to leptin. Adiponectin receptor 1 and 2 (AdipoR1 and R2) mRNA levels in liver and skeletal muscle were normal but hepatic insulin receptor mRNA was increased. Relative to double-mutant males, GHD males had lower levels of insulin, amylin, and leptin, higher levels of adiponectin, and higher expression of hepatic AdipoR1 and insulin receptor mRNAs. Lactogen-resistant mice had reduced hepatic adipoR2 mRNA. In response to stress the plasma concentrations of MCP-1 and IL-6 increased in double-mutant males but not GHD or lactogen-resistant males. Our findings suggest that the insulin resistance of GHD/lactogen-resistant males is accompanied by dysregulation of pancreatic hormone and adipocytokine secretion and receptor expression. Phenotypic differences between double-mutant and GHD males suggest that lactogens and GH exert differential but overlapping effects on fat deposition and adipocytokine secretion and action.
Full Text
Duke Authors
Cited Authors
- Arumugam, R; Fleenor, D; Freemark, M
Published Date
- October 2007
Published In
Volume / Issue
- 32 / 2
Start / End Page
- 182 - 191
PubMed ID
- 17975745
International Standard Serial Number (ISSN)
- 1355-008X
Digital Object Identifier (DOI)
- 10.1007/s12020-007-9017-y
Language
- eng
Conference Location
- United States