Cytosolic free calcium in adipocytes. Distinct mechanisms of regulation and effects on insulin action.
It has been proposed that an elevation in cytosolic free Ca2+ may play a role in either mediating or antagonizing the ability of insulin to stimulate glucose uptake in adipocytes. This question has been addressed in the present studies using isolated fura-2-loaded rat adipocytes stimulated with a variety of agonists. The effects of insulin, oxytocin, norepinephrine, ATP, and ionomycin on cytosolic free Ca2+ levels were assessed and compared with their effects on transport-limited glucose oxidation. Oxytocin and ionomycin at concentrations which caused 3-5-fold increases in cytosolic Ca2+, by releasing Ca2+ from internal stores, had no effect on insulin-stimulated glucose oxidation. ATP and norepinephrine which caused more modest increases in Ca2+, by mechanisms at least partially dependent on external stores, inhibited insulin-stimulated glucose oxidation. Insulin had no effect on basal Ca2+ levels nor did it modulate the Ca2+ elevation caused by other agonists. These data suggest that insulin-stimulated glucose transport is not associated with an increase in cytosolic Ca2+. In addition, although there appears to be a correlation between inhibition of insulin-stimulated glucose transport and the effect of certain agonists to promote Ca2+ influx, there is not a general obligatory relationship between an elevation in cytosolic Ca2+ and antagonism of this insulin action.
Kelly
K L
KL
Division of Diabetes and Metabolism, Boston University School of Medicine, Massachusetts 02118-2393.
Deeney
J T
JT
Corkey
B E
BE
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010121:Oxytocin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D010121:Oxytocin; D000255:Adenosine Triphosphate; D005947:Glucose; D002118:Calcium; D009638:Norepinephrine