Mechanism of glucose intolerance in mice with dominant negative mutation of CEACAM1.

American Journal of Physiology. Endocrinology and Metabolism
So-Young ParkJason K Kim

Abstract

Mice with liver-specific overexpression of dominant negative phosphorylation-defective S503A-CEACAM1 mutant (L-SACC1) developed chronic hyperinsulinemia resulting from blunted hepatic clearance of insulin, visceral obesity, and glucose intolerance. To determine the underlying mechanism of altered glucose homeostasis, a 2-h hyperinsulinemic euglycemic clamp was performed, and tissue-specific glucose and lipid metabolism was assessed in awake L-SACC1 and wild-type mice. Inactivation of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) caused insulin resistance in liver that was mostly due to increased expression of fatty acid synthase and lipid metabolism, resulting in elevated intrahepatic levels of triglyceride and long-chain acyl-CoAs. Whole body insulin resistance in the L-SACC1 mice was further attributed to defects in insulin-stimulated glucose uptake in skeletal muscle and adipose tissue. Insulin resistance in peripheral tissues was associated with significantly elevated intramuscular fat contents that may be secondary to increased whole body adiposity (assessed by (1)H-MRS) in the L-SACC1 mice. Overall, these results demonstrate that L-SACC1 is a mouse model in which chronic hyperinsulinemia acts as a ca...Continue Reading

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Citations

Jan 26, 2012·American Journal of Physiology. Endocrinology and Metabolism·Zhiyou ZhangJason K Kim
Feb 17, 2010·Endocrine Reviews·Mary-Elizabeth Patti, Silvia Corvera
Aug 28, 2012·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·William K WedinAntonio J Convit
Nov 22, 2013·Seminars in Immunopathology·Sonia M Najjar, Lucia Russo
Oct 29, 2011·Phytotherapy Research : PTR·Seo Hee LeeHyun Chul Lee
Sep 2, 2009·Diabetes·David H WassermanOwen P McGuinness
Oct 26, 2016·Journal of Lipid Research·Lucia RussoSonia M Najjar
Apr 11, 2019·Physiology·Sonia M Najjar, Germán Perdomo
Jul 11, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jianfeng XuJane J Kim
Nov 16, 2007·American Journal of Physiology. Endocrinology and Metabolism·Sihoon LeeMichael J Quon
Apr 12, 2017·Frontiers in Endocrinology·Garrett HeinrichSonia M Najjar
May 5, 2016·American Journal of Physiology. Endocrinology and Metabolism·Josef A VogtChristian Denzer
Jul 19, 2020·International Journal of Environmental Research and Public Health·Mohamed A ElrayessAbdelhamid Kerkadi

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