Insulin receptors along the rat nephron: [125I] Insulin binding in microdissected glomeruli and tubules

Abstract

Binding of [125I] Tyr A14 human insulin ([125I] insulin) was measured at 4 degrees C in glomeruli and pieces of tubule microdissected from collagenase-treated rat kidneys. For glomeruli and all segments tested, total and non specific binding increased linearly with glomeruli number or tubular length. When determined with 4.0 nM labelled hormone, the distribution of specific binding sites (expressed as 10(-18) mol [125I] insulin bound per glomerulus or mm tubule length) was as follows: glomerulus, 2.5 +/- 0.3; proximal convoluted tubule (PCT), 12.6 +/- 0.6; pars recta (PR), 4.0 +/- 2.6; thin descending limb (TDL), 0.6 +/- 0.2; thin ascending limb (TAL), 0.6 +/- 0.2; medullary thick ascending limb (MAL), 0.8 +/- 0.1; cortical ascending limb (CAL), 2.1 +/- 0.1; distal convoluted tubule (DCT), 5.6 +/- 1.1; cortical collecting tubule (CCT), 3.2 +/- 0.3 and outer medullary collecting tubule (MCT), 2.3 +/- 0.1. Specific [125I] insulin binding to glomeruli and tubule segments was time and dose-dependent, saturable, reversible after elimination of free labelled ligand, and inhibited by unlabelled human insulin. When analysed in Scatchard and Hill coordinates, the binding data revealed a negative cooperation in the interaction processes between [125I] insulin and glomerular and tubular binding sites, with apparent dissociation constants and Hill coefficients of the following values: glomerulus, 0.6 nM and 0.60; PCT, 10.0 nM and 0.55; MAL, 4.3 nM and 0.80; CAL, 2.0 nM and 0.74; CCT, 7.6 nM and 0.80 and MCT, 1.0 nM and 0.57 respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic syndrome and renal sodium handling in three ethnic groups living in England

“…In humans, insulin has an acute antinatriuretic effect [20], even in obese persons resistant to other metabolic effects of the hormone [21]. Although insulin is thought primarily to affect distal tubular sodium re-absorption [21,22,23,24], there is evidence of a direct insulin action on proximal tubular sodium re-absorption [25,26]; moreover, insulin receptors have been found in the proximal tubule of different species [27,28,29]. Finally, insulin increases the expression and the activity of sodium-hydrogen exchange isoform 3, which mediates more than 60% of the sodium re-absorption at the proximal tubule [30].…”

Regulation of blood pressure, the epithelial sodium channel (ENaC), and other key renal sodium transporters by chronic insulin infusion in rats

“…In situ binding studies using 125 I-labeled insulin have revealed that insulin receptors are localized along the entire length of the renal tubule, with the density the greatest in the thick ascending limb and distal convoluted tubule (12,43). In addition, investigators, utilizing renal micropuncture, have reported that insulin is sodium retentive in the thick ascending limb (30) and/or distal tubule (including thick ascending limb through the collecting duct) (14).…”

C-Peptide stimulates Na+,K+-ATPase activity via PKC alpha in rat medullary thick ascending limb

“…Na + ,K + -ATPase activity in MTAL results mostly from a continuous stimulation through the cAMP-PKA-dependent pathway and regulatory inhibition [13]. In rat MTAL, insulin displays a small stimulatory effect on Na + reabsorption [14] probably due to poor expression of insulin receptors [15]. In addition, insulin does not stimulate Na + ,K + -ATPase activity in the thick ascending limb [16].…”