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Influence of annexin A7 on insulin sensitivity of cellular glucose uptake

  • Integrative physiology
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Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

Insulin sensitivity is decreased by prostaglandin E2 (PGE2), a major product of cyclooxygenase (COX). As shown in erythrocytes, PGE2 formation is inhibited by annexin A7. The present study defined the role of annexin A7 in glucose metabolism. Gene-targeted mice lacking annexin A7 (annexin7 −/−) were compared to wild-type mice (annexin7 +/+). The serum 6-Keto-prostaglandin-F1α (6-Keto-PGF1α) concentration was measured by ELISA and hepatic COX activity determined by an enzyme assay. Expression of COX-1, COX-2, prostaglandin E synthase, GLUT-4, and insulin receptor was determined by Western blotting. Glucose and insulin serum concentrations were analyzed following an intraperitoneal glucose load and glucose serum levels after intraperitoneal injection of insulin. Experiments were done without and with pretreatment of the mice with COX-inhibitor aspirin. The serum 6-Keto-PGF1α level and hepatic COX activity were significantly higher in annexin7 −/− than in annexin7 +/+ mice. Hepatic COX-1 expression was higher in annexin7 −/− mice. Glucose tolerance was decreased in annexin7 −/− mice. Intraperitoneal insulin injection decreased the serum glucose level in both genotypes, an effect significantly less pronounced in annexin7 −/− mice. Glucose-induced insulin secretion was higher in annexin7 −/− mice. GLUT-4 expression in skeletal muscle from annexin7 −/− mice was reduced. Aspirin pretreatment lowered the increase in insulin concentration following glucose injection in both genotypes and virtually abrogated the differences in serum insulin between the genotypes. Aspirin pretreatment improved glucose tolerance in annexin7 −/− mice. In conclusion, annexin A7 influences insulin sensitivity of cellular glucose uptake and thus glucose tolerance. These effects depend on COX activity.

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Acknowledgments

This work was supported by grants from the DFG (Fo 695/1-1 and SFB 773). The authors gratefully acknowledge the meticulous preparation of the manuscript by Lejla Subasic and Sari Rübe and the biometric support for the animal experiments by Martin Eichner.

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Authors and Affiliations

  1. Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany

    Dong Luo, Abul Fajol, Anja T. Umbach, Florian Lang & Michael Föller

  2. Center for Biochemistry, Institute of Biochemistry I, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 52, 50931, Köln, Germany

    Angelika A. Noegel

  3. Department of Pharmaceutical Chemistry, University of Tübingen, Auf der Morgenstelle 8, 72076, Tübingen, Germany

    Stefan Laufer

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  1. Dong Luo
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  2. Abul Fajol
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Correspondence to Michael Föller.

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Dong Luo and Abul Fajol contributed equally.

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Luo, D., Fajol, A., Umbach, A.T. et al. Influence of annexin A7 on insulin sensitivity of cellular glucose uptake. Pflugers Arch - Eur J Physiol 467, 641–649 (2015). https://doi.org/10.1007/s00424-014-1541-z

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  • DOI: https://doi.org/10.1007/s00424-014-1541-z

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