Dopamine 1 Receptor Regulates the Expression of the Insulin Receptor and Insulin Signaling Pathway in Human Renal Proximal Tubule Cells

Dopamine 1 receptor (D 1 R) is dysfunctional in hypertension and diabetes, and fenoldopam (D 1 ‐like receptor agonist) improves the decreased insulin sensitivity in diabetic rats. We hypothesized that the D 1 R interacts with the insulin receptor and regulates its function and signaling pathway in human renal proximal tubule cells (hPTCs). In vehicle‐ and insulin (100nM)‐treated hPTCs (n=3), the D 1 R co‐localizes with the insulin receptor beta subunit (IRβ) (laser scanning confocal microscopy) and the co‐localization increases at 5, 15, and 30 min in the perinuclear area. D 1 R and IRβ also co‐localize in the brush border of proximal tubules of the human kidney. D 1 R and IRβ co‐immunoprecipitate in the basal state and after insulin treatment (100nM, 30 min, n=3), indicating that the two receptors physically interact. hPTCs stably expressing D 1 R‐shRNA had a 60% (39.5±1.1, n=3) decrease in D 1 R protein expression compared with empty vector (EV)‐transfected hPTCs (100±10.6). The decrease in D 1 R expression was associated with a ~40% decrease (57±3.16, n=3) in IRβ expression and a ~69% (31.6±2.6, n=3) decrease in phosphorylated Akt (pAkt) compared with EV‐transfected hPTCs (100±2.04). Our data indicate that the D 1 R regulates the expression of the insulin receptor and D 1 R down‐regulation impairs the insulin signaling pathway (insulin‐IR‐PI 3 K‐Akt).