Chelation of intracellular calcium blocks insulin action in the adipocyte.

Abstract:

:The hypothesis that intracellular Ca2+ is an essential component of the intracellular mechanism of insulin action in the adipocyte was evaluated. Cells were loaded with the Ca2+ chelator quin-2, by preincubating them with quin-2 AM, the tetrakis(acetoxymethyl) ester of quin-2. Quin-2 loading inhibited insulin-stimulated glucose transport (IC50, 26 microM quin-2 AM) without affecting basal activity. The ability of insulin to stimulate glucose uptake in quin-2-loaded cells could be partially restored by preincubating cells with buffer supplemented with 1.2 mM CaCl2 and the Ca2+ ionophore A23187. These conditions had no effect on basal activity and omission of CaCl2 from the buffer prevented the restoration of insulin-stimulated glucose uptake by A23187. Quin-2 loading also inhibited insulin-stimulated glucose oxidation (IC50, 11 microM quin-2 AM) and the ability of insulin to inhibit cAMP-stimulated lipolysis (IC50, 78 microM quin-2 AM), without affecting their basal activities. Incubation of cells with 100 microM quin-2 or quin-2 AM had no effect on intracellular ATP concentration or the specific binding of 125I-labeled insulin to adipocytes. These findings suggest that intracellular Ca2+ is an essential component in the coupling of the insulin-activated receptor complex to cellular physiological/metabolic machinery. Furthermore, differing quin-2 AM dose-response profiles suggest the presence of dual Ca2+-dependent pathways in the adipocyte. One involves insulin stimulation of glucose transport and oxidation, whereas the other involves the antilipolytic action of insulin.

authors

Pershadsingh HA,Shade DL,Delfert DM,McDonald JM

doi

10.1073/pnas.84.4.1025

subject

Has Abstract

pub_date

1987-02-01 00:00:00

pages

1025-9

issue

4

eissn

0027-8424

issn

1091-6490

journal_volume

84

pub_type

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