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- Title
Role of CEACAM2 in Insulin Action.
- Authors
Schroeder-Gloeckler, Jill; Deangelis, Anthony; Tong Dai; Heinrich, Garrett; Al-Share, Qusai; Sang Jun Lee; Dai Young Jung; Zhiyou Zhang; Eun-Gyoung Hong; Kim, Jason; Najjar, Sonia
- Abstract
The insulin receptor substrate CEACAM1 plays a role in insulin clearance in liver. A related gene, CEACAM2, is mostly expressed in β-cells, hypothalamus and kidney. To investigate its function, we generated Ceacam2 knockout mice (Cc2[sup -/-]) and examined their metabolic profile. Female mice lacking Cc2 exhibit higher body weight and visceral obesity in addition to total fat and lean mass (measured using ¹H-MRS) starting at 2 months of age, at which point they also develop hyperinsulinemia as compared to their wild type (Cc2[sup +/+]) littermates. In contrast to Cc1[sup -/-] mice, insulin clearance is not reduced in Cc2[sup -/-] null mice at 2, 4 and 6 months of age, consistent with the relative low abundance of CEACAM2 in liver and normal levels of CEACAM1 in Cc2[sup -/-] mice. These findings suggest that hyperinsulinemia results primarily from altered insulin secretion. Cc2[sup -/-]mice display impaired first-phase insulin secretion in response to a glucose challenge, with increased second phase. They also show reduced glucose tolerance and fasting hyperglycemia, consistent with peripheral insulin resistance. This conclusion was supported by in vivo hyperinsulinemic (2.5 mU/kg/min)-euglycemic clamps that revealed reduced glucose infusion and turnover rates in addition to lower glycogen synthesis. Clamp studies and insulin receptor phosphorylation indicated normal hepatic insulin action and normal glucose uptake in skeletal muscle. With plasma triglyceride levels being reduced, we propose that the observed phenotype is due to reduced glucose uptake in fat tissue, arising from increased triglyceride flux and lipogenesis in this tissue. The data indicate a novel mechanism by which CEACAM proteins regulate metabolism.
- Subjects
INSULIN receptors; LIVER; PANCREATIC beta cells; HYPOTHALAMUS; KIDNEYS; GLUCOSE; HYPERGLYCEMIA; ADIPOSE tissues
- Publication
Diabetes, 2007, Vol 56, pA343
- ISSN
0012-1797
- Publication type
Article