Regulation of insulin-stimulated glucose transport in the isolated rat adipocyte. cAMP-independent effects of lipolytic and antilipolytic agents

M. Kuroda, R. C. Honnor, S. W. Cushman, C. Londos, I. A. Simpson

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This paper examines the modulation of insulin-stimulated glucose transport activity in rat adipose cells by ligands for receptors (R) that mediate stimulation (R(s); lipolytic) or inhibition (R(i); antilipolytic) of adenylate cyclase. The changes in glucose transport activity and cAMP, as assessed by 3-O-methylglucose uptake and (-/+) cAMP-dependent protein kinase (A-kinase) activity ratios, respectively, were monitored under conditions that maintain steady-state A-kinase activity ratios. Removal of endogenous adenosine with adenosine deaminase decreased insulin-stimulated glucose transport activity by ~ 30%, which was prevented or restored with R(i) agonists such as phenylisopropyladenosine, nicotinic acid, and prostaglandin E1. These changes in transport activity were not accompanied by changes in A-kinase activity ratios, indicating that R(i)-mediated effects on transport are independent of cAMP changes. Addition of an R(s) ligand, isoproterenol, in the presence of adenosine increased kinase activity but did not change glucose transport activity. Conversely, upon removal of adenosine, addition of R(s) ligands such as isoproterenol, adrenocorticotropic hormone, or glucagon strongly inhibited transport (~ 50%) and stimulated kinase activity. However, subsequent addition of phenylisopropyladenosine nearly restored transport activity without alteration of A-kinase activity. These data and additional kinetic experiments suggest that R(s)-mediated glucose transport modulations are also independent of cAMP. The interchangeability of ligands for both R(s) and R(i) receptors in modulating transport activity suggests that these cAMP-independent effects are mediated by the stimulatory (N(s)) and inhibitory (N(i)) guanyl nucleotide-binding regulatory proteins of adenylate cyclase. All R(s)- and R(i)-induced changes in transport activity occurred without a change in glucose transporter distribution, as assessed by D-glucose-inhibitable cytochalasin B binding, suggesting that R(s) and R(i) ligands modulate the intrinsic activity of the glucose transporter present in the plasma membrane.

Original languageEnglish (US)
Pages (from-to)245-253
Number of pages9
JournalJournal of Biological Chemistry
Issue number1
StatePublished - 1987

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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