A Role for CEACAM2 protein in Insulin Secretion, Clearance and Action

A Role for CEACAM2 protein in Insulin Secretion, Clearance and Action

Bibliographic Details
Main Author: Ghanem, Simona S.
Language:English
Published: University of Toledo Health Science Campus / OhioLINK 2017
Subjects:
Biomedical Research
Molecular Biology
Physiology
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=mco1491497714470047
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-mco14914977144700472021-08-03T07:01:21Z A Role for CEACAM2 protein in Insulin Secretion, Clearance and Action Ghanem, Simona S. Biomedical Research Molecular Biology Physiology The carcinoembryonic antigen related cell adhesion molecule (CEACAM) family is agroup of proteins reported to have potent roles in insulin signaling, lipogenesis,immunity, and tumor suppression. To investigate the role of CEACAM2, we have used amurine model with global Ceacam2 gene deletion. The male Ceacam2 knockout miceshowed an increase in insulin release suggesting that CEACAM2 plays an important rolein regulating insulin secretion. Due to the low expression of Ceacam2 in beta pancreaticcells, CEACAM2 effect on insulin secretion was caused by an extra-pancreaticmechanism. Consistent to the expression of CEACAM2 in the distal intestinal villi, nullCEACAM2 male mice showed a higher excursion of GLP-1 in response to oraladministration of glucose, showing that the CEACAM2 effect on insulin secretion ismediated partly via a GLP-1 dependent mechanism. In accordance with the importance ofinsulin clearance in the kidney to maintain normal plasma insulin levels and CEACAM2expression in proximal tubule cells, mutant male mice revealed an impairment in renalinsulin clearance reflecting its function in regulating insulin extraction in the kidney.These data also imply that CEACAM2 is an insulin receptor substrate that undergoesphosphorylation at its intra cellular phosphorylation sites during insulin stimulation tomediate receptor-mediated endocytosis in proximal tubule cells. Despite the hyperphagiaof all age groups, Ceacam2 knockout male mice are insulin sensitive till the age of 9months. We also show that insulin resistance, obesity and hyperinsulinemia did not startuntil 9 months of age likely due to reduced energy expenditure and increased free fattyacids. In addition, CEACAM1 levels are reduced during that age group explaining theinsulin resistance and reflecting the low insulin clearance (low C/I molar ratio). Thisillustrates that insulin resistance in these mutant mice is age dependent. These reportsexpand our understanding of the role of CEACAM2 protein in the regulation of insulinsecretion and insulin action. 2017-10-18 English text University of Toledo Health Science Campus / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=mco1491497714470047 http://rave.ohiolink.edu/etdc/view?acc_num=mco1491497714470047 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Biomedical Research
Molecular Biology
Physiology
spellingShingle Biomedical Research
Molecular Biology
Physiology
Ghanem, Simona S.
A Role for CEACAM2 protein in Insulin Secretion, Clearance and Action
author Ghanem, Simona S.
author_facet Ghanem, Simona S.
author_sort Ghanem, Simona S.
title A Role for CEACAM2 protein in Insulin Secretion, Clearance and Action
title_short A Role for CEACAM2 protein in Insulin Secretion, Clearance and Action
title_full A Role for CEACAM2 protein in Insulin Secretion, Clearance and Action
title_fullStr A Role for CEACAM2 protein in Insulin Secretion, Clearance and Action
title_full_unstemmed A Role for CEACAM2 protein in Insulin Secretion, Clearance and Action
title_sort role for ceacam2 protein in insulin secretion, clearance and action
publisher University of Toledo Health Science Campus / OhioLINK
publishDate 2017
url http://rave.ohiolink.edu/etdc/view?acc_num=mco1491497714470047
work_keys_str_mv AT ghanemsimonas aroleforceacam2proteinininsulinsecretionclearanceandaction
AT ghanemsimonas roleforceacam2proteinininsulinsecretionclearanceandaction
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