Regulation of insulin action by CEACAM1

Trends Endocrinol Metab. 2002 Aug;13(6):240-5. doi: 10.1016/s1043-2760(02)00608-2.


Activation of the tyrosine kinase of the insulin receptor by insulin binding initiates a cascade of signaling pathways that mediates the metabolic and growth-promoting effects of insulin. Insulin action is regulated by the amount of circulating insulin, which is, in turn, partially regulated by insulin clearance in liver. Receptor-mediated insulin endocytosis followed by degradation mediates insulin clearance. Earlier studies in transfected cells suggested that the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), a substrate of the insulin receptor in liver, upregulates receptor-mediated insulin endocytosis and degradation in a phosphorylation-dependent manner. To test this hypothesis, a transgenic mouse, L-SACC1, overexpressing a dominant-negative phosphorylation-defective S503A CEACAM1 mutant in liver was established. The transgenic mouse demonstrated that CEACAM1 increases insulin clearance to maintain insulin sensitivity. Because insulin resistance is the hallmark of type 2 diabetes, understanding the mechanism of CEACAM1 regulation of insulin clearance and action might lead to novel therapeutic strategies against this disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Antigens, CD / chemistry
  • Antigens, CD / genetics
  • Antigens, CD / physiology*
  • Antigens, Differentiation / chemistry
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / physiology*
  • Carcinoembryonic Antigen
  • Cell Adhesion Molecules
  • Gene Expression
  • Homeostasis
  • Insulin / metabolism
  • Insulin / pharmacology*
  • Liver / metabolism
  • Mice
  • Mice, Transgenic
  • Mutation
  • Phosphorylation
  • Receptor, Insulin / metabolism


  • Antigens, CD
  • Antigens, Differentiation
  • CD66 antigens
  • Carcinoembryonic Antigen
  • Ceacam1 protein, mouse
  • Cell Adhesion Molecules
  • Insulin
  • Receptor, Insulin