Correction of enhanced Na(+)-H+ exchange of rat small intestinal brush-border membranes in streptozotocin-induced diabetes by insulin or 1,25-dihydroxycholecalciferol

Journal Article · Wed May 01 04:00:00 EDT 1991 · Journal of Clinical Investigation; (USA)

DOI:https://doi.org/10.1172/JCI115194· OSTI ID:5734773

Dudeja, P K; Wali, R K; Klitzke, A; Sitrin, M D; Brasitus, T A ^[1]

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1. Univ. of Chicago, IL (USA)

Diabetes was induced in rats by administration of a single i.p. injection of streptozotocin (50 mg/kg body wt). After 7 d, diabetic rats were further treated with insulin or 1,25-dihydroxycholecalciferol (1,25(OH)2D3) for an additional 5-7 d. Control, diabetic, diabetic + insulin, and diabetic + 1,25(OH)2D3 rats were then killed, their proximal small intestines were removed, and villus-tip epithelial cells were isolated and used to prepare brush-border membrane vesicles. Preparations from each of these groups were then analyzed and compared with respect to their amiloride-sensitive, electroneutral Na(+)-H+ exchange activity, using {sup 22}Na uptake as well as acridine orange techniques. The results of these experiments demonstrated that (a) H+ gradient-dependent {sup 22}Na uptake as well as Na+ gradient-dependent transmembrane H+ fluxes were significantly increased in diabetic vesicles compared to their control counterparts, (b) kinetic studies demonstrated that this enhanced {sup 22}Na uptake in diabetes was a result of increased maximal velocity (Vmax) of this exchanger with no change in apparent affinity (Km) for Na+, (c) serum levels of 1,25(OH)2D3 were significantly lower in diabetic animals compared with their control counterparts; and (d) insulin or 1,25(OH)2D3 treatment restored the Vmax alterations to control values, without any significant changes in Km, concomitant with significantly increasing the serum levels of 1,25(OH)2D3 in diabetic animals. These results indicate that Na(+)-H+ activity is significantly increased in proximal small intestinal luminal membranes of streptozotocin-induced diabetic rats. Moreover, alterations in the serum levels of 1,25(OH)2D3 may, at least in part, explain this enhanced antiporter activity and its correction by insulin.

• OSTI ID: 5734773
• Journal Information: Journal of Clinical Investigation; (USA), Journal Name: Journal of Clinical Investigation; (USA) Vol. 87:5; ISSN 0021-9738; ISSN JCINA
• Country of Publication: United States
• Language: English

Related Subjects

550901* -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALI METAL COMPOUNDS
ALKALI METAL ISOTOPES
ANIMALS
BARYONS
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BODY
CELL CONSTITUENTS
CELL MEMBRANES
DIABETES MELLITUS
DIGESTIVE SYSTEM
DISEASES
ELEMENTARY PARTICLES
ENDOCRINE DISEASES
FERMIONS
GASTROINTESTINAL TRACT
HADRONS
HORMONES
INSULIN
INTESTINES
ION EXCHANGE
ISOMERIC TRANSITION ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MAMMALS
MEMBRANE TRANSPORT
MEMBRANES
METABOLIC DISEASES
NANOSEC LIVING RADIOISOTOPES
NUCLEI
NUCLEONS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PATHOGENESIS
PEPTIDE HORMONES
PROTEINS
PROTONS
RADIOISOTOPES
RATS
RODENTS
SMALL INTESTINE
SODIUM 22
SODIUM COMPOUNDS
SODIUM ISOTOPES
TRACER TECHNIQUES
VERTEBRATES
YEARS LIVING RADIOISOTOPES