title: Antiaging gene Klotho enhances glucose-induced insulin secretion by up-regulating plasma membrane levels of TRPV2 in MIN6 β-cells.
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 plasma membrane levels of TRPV2 and attenuated 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.
authors.affiliation: Department of Physiology, College of Medicine, University of Oklahoma Health Sciences Center, 940 S. L. Young Boulevard, Oklahoma City, Oklahoma 73126-0901, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lin
authors.forename: Zhongjie
authors.initials: Z
authors.lastname: Sun
mesh_terms: D000375:Aging; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D005966:Glucuronidase / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology*; D007515:Islets of Langerhans / Q000166:cytology; D000090265:Klotho Proteins; D051379:Mice; D034741:RNA, Small Interfering / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D015220:Calcium Channels; D007328:Insulin; D034741:RNA, Small Interfering; D050916:TRPV Cation Channels; C485717:Trpv2 protein, mouse; D005966:Glucuronidase; D000090265:Klotho Proteins; D005947:Glucose; D002118:Calcium