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Insulin receptor localization and regulation in rat kidney
Author(s) -
Tiwari Swasti,
Wade James B.,
Ecelbarger Carolyn A.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1169
Subject(s) - medicine , endocrinology , hyperinsulinemia , insulin , distal convoluted tubule , kidney , rosiglitazone , insulin receptor , chemistry , renal medulla , biology , reabsorption , insulin resistance
Insulin is anti‐natriuretic. However, few studies have examined renal insulin receptor (IR) expression and regulation at the protein level. We examined insulin as a modifier of its own receptor in two rat models of hyperinsulinemia: 1) 18 male SD rats were assigned (270g, n = 6/group) to receive either vehicle plus water to drink, insulin‐infusion (20 U/kg·bw/day) plus 20% dextrose to drink, or vehicle plus 20% dextrose; 2) male obese (endogenously hyperinsulinemic) and lean Zucker rats (n = 12/body type) were assigned to receive either control diet or this diet with rosiglitazone, an insulin sensitizer (RGZ, 3 mg/kg·bw/day) for 12 weeks. RGZ reduced plasma insulin in obese rats. Immunofluorescence using a β‐subunit antibody revealed that the IR was expressed in proximal tubule, thick ascending limb, distal tubule and collecting duct. In the distal tubule, IR colocalized with the thiazide‐sensitive Na‐Cl cotransporter and aquaporin 2, indicating its presence in both distal convoluted tubule cells and in principal cells of collecting duct. Immunoblotting showed a significant increase (138% of control) in IR band density (97 kDa) in the whole kidney of insulin‐infused rats relative to vehicle. Regional analysis demonstrated this increase was primarily in cortex (CTX), as there was a trend for a decrease in the outer (OM) and inner medulla (IM). In contrast, the obese Zucker rats had significantly decreased abundance of IR in the CTX and IM, relative to lean rats, with a selective, significant increase in OM abundance. RGZ treatment did not affect the abundance of IR in either lean or obese rats. In conclusion, the IR is expressed along the length of the renal tubule and is variably regulated during hyperinsulinemia which may impact on renal sodium reabsorption. Funded by NIH.