title: Stimulatory effect of insulin on renal proximal tubule sodium transport is preserved in type 2 diabetes with nephropathy.
abstract: Our previous study indicates that hyperinsulinemia in metabolic syndrome in the absence of nephropathy may promote hypertension by stimulating renal proximal tubule (PT) sodium transport via insulin receptor substrate (IRS) 2/phosphoinositide 3-kinase pathway. In the present study we showed that the stimulatory effect of insulin on the Na(+)-HCO3(-) cotransporter NBCe1 in isolated PTs was completely preserved in type 2 diabetic rats with overt nephropathy. Furthermore, the IRS2 expression and insulin-induced Akt phosphorylation in kidney cortex were preserved in these rats. By contrast, the IRS1 expression in kidney cortex was markedly reduced, which might be relevant to enhanced renal gluconeogenesis consistently reported in diabetes. The stimulatory effect of insulin on NBCe1 was preserved also in a human type 2 diabetic patient with advanced nephropathy. These results revealed that insulin can stimulate PT sodium transport even in type 2 diabetes with overt nephropathy. In addition to hypoglycemia, insulin-induced renal sodium retention might also play a role in increased cardiovascular risk associated with intensive glycemic control in type 2 diabetic patients with nephropathy.
authors: Department of Internal Medicine, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors: Motonobu
authors: M
authors: Nakamura
authors: Department of Internal Medicine, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors: Nobuhiko
authors: N
authors: Satoh
authors: Department of Internal Medicine, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors: Masashi
authors: M
authors: Suzuki
authors: Department of Urology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors: Haruki
authors: H
authors: Kume
authors: Department of Urology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors: Yukio
authors: Y
authors: Homma
authors: Department of Internal Medicine, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors: George
authors: G
authors: Seki
authors: Department of Internal Medicine, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Electronic address: shorita-tky@umin.ac.jp.
authors: Shoko
authors: S
authors: Horita
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007328:Insulin / Q000008:administration & dosage*; D015640:Ion Channel Gating / Q000187:drug effects*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D012964:Sodium / Q000378:metabolism*; D027982:Sodium-Bicarbonate Symporters / Q000378:metabolism*
chemical_list: D007328:Insulin; C498898:SLC4A4 protein, human; D027982:Sodium-Bicarbonate Symporters; D012964:Sodium
keywords: Diabetic nephropathy; IRS2; Insulin; NBCe1; Renal proximal tubules; Type 2 diabetes