Antiaging gene Klotho enhances glucose-induced insulin secretion by up-regulating plasma membrane levels of TRPV2 in MIN6 β-cells

Yi Lin, Zhongjie Sun

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Klotho is a recently discovered antiaging gene. Klotho is expressed in mouse pancreatic islets and in insulinoma β-cells (MIN6 β-cells). The purpose of this study was to investigate whether Klotho plays a role in the regulation of insulin secretion in MIN6 β-cells by overexpression and silencing of Klotho. It is interesting that overexpression of Klotho increased glucose-induced insulin secretion in MIN6 β-cells. Overexpression of mouse Klotho protein also significantly increased plasma membrane levels of transient receptor potential V2 (TRPV2), calcium entry, and the glucose-induced increase in intracellular calcium. On the other hand, knockdown of Klotho by siRNA significantly decreased plasmamembranelevels ofTRPV2andattenuated glucose-induced calcium entry and insulin secretion. Tranilast, a selective inhibitor of TRPV2, abolished the promoting effects of overexpression of Klotho on glucose-induced calcium entry and insulin secretion in MIN6 cells. Thus, TRPV2 lies in the downstream of Klotho in the regulation of glucose-induced insulin secretion. This study demonstrated, for the first time, that Klotho may enhance glucose-induced insulin secretion by up-regulating plasma membrane levels of TRPV2 and thus glucose-induced calcium responses. These findings reveal a previously unidentified role of Klotho in the regulation of glucose-induced insulin secretion in MIN6 β-cells.

Original languageEnglish (US)
Pages (from-to)3029-3039
Number of pages11
JournalEndocrinology
Volume153
Issue number7
DOIs
StatePublished - Jul 1 2012

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Vasopressin Receptors
Cell Membrane
Insulin
Glucose
Genes
Calcium
Insulinoma
Islets of Langerhans
Small Interfering RNA

All Science Journal Classification (ASJC) codes

  • Endocrinology

Cite this

Antiaging gene Klotho enhances glucose-induced insulin secretion by up-regulating plasma membrane levels of TRPV2 in MIN6 β-cells. / Lin, Yi; Sun, Zhongjie.

In: Endocrinology, Vol. 153, No. 7, 01.07.2012, p. 3029-3039.

Research output: Contribution to journalArticle

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