Insulin Induces Calcium Signals in the Nucleus of Rat Hepatocytes

Overview

Journal Hepatology

Specialty Gastroenterology

Date 2008 Sep 18

PMID 18798337

Citations 34

Authors

Michele A Rodrigues

Dawidson A Gomes

Viviane A Andrade

M Fatima Leite

Michael H Nathanson

Affiliations

Soon will be listed here.

Abstract

Insulin is an hepatic mitogen that promotes liver regeneration. Actions of insulin are mediated by the insulin receptor, which is a receptor tyrosine kinase. It is currently thought that signaling via the insulin receptor occurs at the plasma membrane, where it binds to insulin. Here we report that insulin induces calcium oscillations in isolated rat hepatocytes, and that these calcium signals depend upon activation of phospholipase C and the inositol 1,4,5-trisphosphate receptor, but not upon extracellular calcium. Furthermore, insulin-induced calcium signals occur in the nucleus, and are temporally associated with selective depletion of nuclear phosphatidylinositol bisphosphate and translocation of the insulin receptor to the nucleus. These findings suggest that the insulin receptor translocates to the nucleus to initiate nuclear, inositol 1,4,5-trisphosphate-mediated calcium signals in rat hepatocytes. This novel signaling mechanism may be responsible for insulin's effects on liver growth and regeneration.

Citing Articles

Decoding how receptor tyrosine kinases (RTKs) mediate nuclear calcium signaling.

Armijos M, Bassani T, Fernandez C, Rodrigues M, Gomes D Adv Biol Regul. 2024; 92:101033.

PMID: 38739986 PMC: 11156257. DOI: 10.1016/j.jbior.2024.101033.

CD38/ADP-ribose/TRPM2-mediated nuclear Ca signaling is essential for hepatic gluconeogenesis in fasting and diabetes.

Rah S, Joe Y, Park J, Ryter S, Park C, Chung H Exp Mol Med. 2023; 55(7):1492-1505.

PMID: 37394593 PMC: 10393965. DOI: 10.1038/s12276-023-01034-9.

The basis of nuclear phospholipase C in cell proliferation.

Gomes D, de Miranda M, Faria J, Rodrigues M Adv Biol Regul. 2021; 82:100834.

PMID: 34710785 PMC: 8671340. DOI: 10.1016/j.jbior.2021.100834.

The role of nuclear Ca2+ in maintaining neuronal homeostasis and brain health.

Mozolewski P, Jeziorek M, Schuster C, Bading H, Frost B, Dobrowolski R J Cell Sci. 2021; 134(8).

PMID: 33912918 PMC: 8084578. DOI: 10.1242/jcs.254904.

Molecular Mechanism for Protection Against Liver Failure in Human Yellow Fever Infection.

de Oliveira Lemos F, Franca A, Lima Filho A, Florentino R, Santos M, Missiaggia D Hepatol Commun. 2020; 4(5):657-669.

PMID: 32363317 PMC: 7193135. DOI: 10.1002/hep4.1504.

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