Insulin binding sites in various segments of the rabbit nephron

Journal Article · Fri Jul 01 00:00:00 EDT 1983 · J. Clin. Invest.; (United States)

DOI:https://doi.org/10.1172/JCI110979· OSTI ID:5544893

Nakamura, R; Emmanouel, D S; Katz, A I

Insulin binds specifically to basolateral renal cortical membranes and modifies tubular electrolyte transport, but the target sites of this hormone in the nephron have not been identified. Using a microassay that permits measurement of hormone binding in discrete tubule segments we have determined the binding sites of /sup 125/I-insulin along the rabbit nephron. Assays were performed under conditions that minimize insulin degradation, and specific binding was measured as the difference between /sup 125/I-insulin bound in the presence or absence of excess (10(-5) M) unlabeled hormone. Insulin monoiodinated in position A14 was used in all assays. Specific insulin binding (attomol . cm-1 +/- SE) was highest in the distal convoluted tubule (180.5 +/- 15.0) and medullary thick ascending limb of Henle's loop (132.9 +/- 14.6), followed by the proximal convoluted and straight tubule. When expressed per milligram protein, insulin binding capacity was highest along the entire thick ascending limb (medullary and cortical portions) and the distal convoluted tubule, i.e., the ''diluting segment'' (congruent to 10(-13) mol . mg protein-1), and was lower (congruent to 4 X 10(-14) mol . mg protein-1), and remarkably similar, in all other nephron segments. Binding specificity was verified in competition studies with unlabeled insulin, insulin analogues (proinsulin and desoctapeptide insulin), and unrelated hormones (glucagon, 1-34 parathyroid hormone, prolactin, follicle-stimulating hormone). In addition, serum containing antiinsulin receptor antibody from two patients with type B insulin resistance syndrome markedly inhibited insulin binding to isolated tubules. Whether calculated per unit tubule length or protein content, insulin binding is highest in the thick ascending limb and the distal convoluted tubule, the same nephron sites where a regulatory role in sodium transport has been postulated for this hormone.

• Research Organization: Department of Medicine, University of Chicago, Pritzker School of Medicine, Illinois
• OSTI ID: 5544893
• Journal Information: J. Clin. Invest.; (United States), Journal Name: J. Clin. Invest.; (United States) Vol. 72:1; ISSN JCINA
• Country of Publication: United States
• Language: English

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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BETA DECAY RADIOISOTOPES
BODY
CHEMICAL PREPARATION
CHEMISTRY
DAYS LIVING RADIOISOTOPES
ELECTROLYTES
ELECTRON CAPTURE RADIOISOTOPES
HORMONES
INSULIN
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KIDNEYS
LABELLED COMPOUNDS
LABELLING
MAMMALS
NUCLEI
ODD-EVEN NUCLEI
ORGANS
PEPTIDE HORMONES
RABBITS
RADIOCHEMISTRY
RADIOISOTOPES
RECEPTORS
SYNTHESIS
TRACER TECHNIQUES
TUBULES
VERTEBRATES