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Differential Role of CEACAM Proteins in Regulating Insulin Metabolism
| Title: | Differential Role of CEACAM Proteins in Regulating Insulin Metabolism |
| Author: | Dai, Tong |
| Description: | The CEACAM1, a substrate of insulin receptor kinase in hepatocytes, promotes receptor-mediated insulin endocytosis and degradation, as demonstrated in L-SACC1 transgenic mice in which impaired insulin clearance causes hyperinsulinemia and hepatic insulin resistance. By decreasing visceral adiposity and circulating FFAs levels, carnitine normalized insulin levels and glucose tolerance in female L-SACC1 mice. Because carnitine does not affect receptor-mediated insulin internalization directly, the data suggest that altered fat metabolism plays an important role in the pathogenesis of impaired insulin clearance and insulin resistance in L-SACC1 mice. Deletion of Ceacam1 led to decreased insulin clearance, consistent with the predominant expression of CEACAM1 in liver, the major site of insulin clearance. In contrast, deletion of its homolog, Ceacam2, led to hyperinsulinemia without altering insulin clearance, in keeping with the low expression of CEACAM2 in liver. Both in vivo first-phase insulin secretion in response to exogenous glucose and glucose-stimulated insulin secretion from isolated islets were impaired in Ceacam2 null mice, whereas these parameters were unchanged in Ceacam1 null mice. Thus, CEACAM1 modulates hepatic insulin clearance and lipid metabolism, whereas CEACAM2 regulates glucose-induced insulin secretion. This study demonstrates non-redundant functions of these two closely related CEACAM proteins in maintaining insulin sensitivity. |
| Permanent Link: |
http://rave.ohiolink.edu/etdc/view?acc_num=mco1139336269
http://hdl.handle.net/2374.OX/18139 |
| Date: | 2005 |
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