PMID: 22580530May 15, 2012Paper

Exendin-4 reduces glycemia by increasing liver glucokinase activity: an insulin independent effect

Pharmacological Reports : PR
Nirav DhaneshaMukul Jain

Abstract

Exendin-4 is a stable peptide agonist of GLP-1 receptor that exhibits insulinotropic actions. Some in vivo studies indicated insulin-independent glucoregulatory actions of exendin-4. That finding prompted us to evaluate effects of exendin-4 on liver glucose metabolism. Acute and chronic treatment of exendin-4 resulted in increased hepatic glucokinase activity in db/db mice but not in lean C57 mice. The stimulatory effect of exendin-4 on glucokinase activity was abrogated by exendin 9-39, a GLP-1 antagonist. Exposure of hepatocytes isolated from db/db mice to exendin-4 elicited a rapid increase in cAMP, which was synergized by IBMX, an inhibitor of cAMP degradation. The GLP-1 antagonist, exendin 9-39, has abolished the cAMP generating effects of exendin-4 as well. Furthermore, chronic treatment of exendin-4 in streptozotocin-treated C57 mice resulted in restoration of hepatic glycogen, an indicator of improved glucose metabolism, without apparent changes in serum insulin levels. In conclusion, exendin-4 increased glucokinase enzyme protein and activity in liver via a mechanism parallel to and independent of insulin. Exendin-4-induced increase in hepatic glucokinase activity is more pronounced in the presence of hepatic insulin r...Continue Reading

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Citations

Oct 27, 2015·Diabetes, Obesity & Metabolism·Mark M SmitsDaniël H van Raalte
Nov 3, 2015·Peptides·Flavio FranciniJuan José Gagliardino
Dec 3, 2015·Canadian Journal of Physiology and Pharmacology·Vishal PatelMukul R Jain
Feb 24, 2012·Journal of Diabetes·Nirav DhaneshaMukul Jain
Mar 18, 2013·Journal of Diabetes Investigation·Yutaka Seino, Daisuke Yabe
May 26, 2016·American Journal of Physiology. Endocrinology and Metabolism·Manjula VinodGerhard M Kostner
Jan 13, 2018·Pathobiology of Aging & Age Related Diseases·Akram AhangarpourMohammad Badavi
Jan 22, 2015·The World Journal of Men's Health·Akram AhangarpourHamid Heidari
May 16, 2013·American Journal of Physiology. Endocrinology and Metabolism·Dale S EdgertonAlan D Cherrington
Mar 16, 2019·Journal of Cellular Biochemistry·Maria J PenaNuno Borges

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