Insulin downregulates the expression of the Ca2+-activated nonselective cation channel TRPM5 in pancreatic islets from leptin-deficient mouse models.
We recently proposed that the transient receptor potential melastatin 5 (TRPM5) cation channel contributes to glucose-induced electrical activity of the β cell and positively influences glucose-induced insulin release and glucose homeostasis. In this study, we investigated Trpm5 expression and function in pancreatic islets from mouse models of type II diabetes. Gene expression analysis revealed a strong reduction of Trpm5 mRNA levels in pancreatic islets of db/db and ob/ob mice. The glucose-induced Ca(2+) oscillation pattern in db/db and ob/ob islets mimicked those of Trpm5 (-/-) islets. Leptin treatment of ob/ob mice not only reversed the diabetic phenotype seen in these mice but also upregulated Trpm5 expression. Leptin treatment had no additional effect on Trpm5 expression levels when plasma insulin levels were comparable to those of the vehicle-injected control group. In murine β cell line, MIN6, insulin downregulated TRPM5 expression in a dose-dependent manner, unlike glucose or leptin. In conclusion, our data show that increased plasma insulin levels downregulate TRPM5 expression in pancreatic islets from leptin-deficient mouse models of type 2 diabetes.
Laboratory of Ion Channel Research, KU Leuven, Herestraat 49, bus 802, Leuven, 3000, Belgium.
Barbara
B
Colsoul
Griet
G
Jacobs
Koenraad
K
Philippaert
Grzegorz
G
Owsianik
Andrei
A
Segal
Bernd
B
Nilius
Thomas
T
Voets
Frans
F
Schuit
Rudi
R
Vennekens
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D015536:Down-Regulation; D017353:Gene Deletion; D007328:Insulin / Q000097:blood*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D020738:Leptin / Q000097:blood*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054411:Receptors, Leptin / Q000235:genetics; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*
D007328:Insulin; D020738:Leptin; D012333:RNA, Messenger; D054411:Receptors, Leptin; D050053:TRPM Cation Channels; C498617:Trpm5 protein, mouse