Chelation of intracellular calcium blocks insulin action in the adipocyte

Journal Article · Sat Jan 31 23:00:00 EST 1987 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.84.4.1025· OSTI ID:5768220

Pershadsingh, H A; Shade, D L; Delfert, D M; McDonald, J M

The hypothesis that intracellular Ca/sup 2 +/ is an essential component of the intracellular mechanism of insulin action in the adipocyte was evaluated. Cells were loaded with the Ca/sup 2 +/ 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 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 CaCl/sub 2/ and the Ca/sup 2 +/ ionophore A23187. These conditions had no effect on basal activity and omission of CaCl/sub 2/ from the buffer prevented the restoration of insulin-stimulated glucose uptake by A23187. Quin-2 loading also inhibited insulin-stimulated glucose oxidation and the ability of insulin to inhibit cAMP-stimulated lipolysis without affecting their basal activities. Incubation of cells with 100 ..mu..M quin-2 or quin-2 AM had no effect on intracellular ATP concentration or the specific binding of /sup 125/I=labeled insulin to adipocytes. These findings suggest that intracellular Ca/sup 2 +/ 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 Ca/sup 2 +/-dependent pathways in the adipocyte. One involves insulin stimulation of glucose transport and oxidation, whereas the other involves the antilipolytic action of insulin.

• Research Organization: Washington Univ. School of Medicine, St. Louis, MO
• OSTI ID: 5768220
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:4; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADIPOSE TISSUE
ALDEHYDES
ALKALINE EARTH METAL COMPOUNDS
ANIMAL CELLS
ANIMAL TISSUES
BETA DECAY RADIOISOTOPES
BODY
CALCIUM COMPOUNDS
CARBOHYDRATES
CARBON 14 COMPOUNDS
CATIONS
CHARGED PARTICLES
CHELATING AGENTS
CONFIGURATION INTERACTION
CONNECTIVE TISSUE
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
FAT CELLS
GLUCOSE
HEXOSES
HORMONES
INSULIN
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
IONS
ISOTOPES
LABELLED COMPOUNDS
MEMBRANE TRANSPORT
MONOSACCHARIDES
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PEPTIDE HORMONES
RADIOISOTOPES
SACCHARIDES
SOMATIC CELLS
TISSUES
TRITIUM COMPOUNDS