Role of cAMP in mediating effects of fasting on dephosphorylation of insulin receptor

N. Begum, A. L. Graham, K. E. Sussman, B. Draznin

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11 Scopus citations


We studied the effect of fasting on phosphotyrosine phosphatase (PTPase) activities in particulate (PF) and cytosolic (CF) fractions of rat adipocytes and liver. PTPase activity was assessed using [32P]tyrosine insulin receptor (IR). In adipocytes, 48 h fasting significantly inhibited PTPase activity. Dephosphorylation of IR by PF and CF PTPases was reduced by 80 and 65%, respectively. Similar reductions of lesser magnitude were observed in fasted rat livers. The effect of fasting was completely reversed by either refeeding or by incubating 'fasted' adipocytes for 2 h in tissue culture medium containing 5 mM glucose. Neither 20 mM glucose nor the presence of insulin influenced phosphatase activity. Because fasting is accompanied by elevated protein kinase C (PKC) and adenosine 3',5'-cyclic monophosphate (cAMP) levels, we examined their influence on adipocyte PTPases. Neither activation (1 μM 12-O-tetradecanoylphorbol-13-acetate) nor inhibition (20 μM sphingosine) of PKC affected PTPase activity. In contrast, cAMP (2 mM) significantly inhibited PTPase activity (80% inhibition at 2 h), and its effect was prevented by a cAMP antagonist RpcAMP. Fasting- and cAMP-induced inhibition of PTPase activity was restored by incubating PF with trypsin (4 μg/ml for 5 min), which separated the putative inhibitors from the phosphatases. We conclude that fasting-induced inhibition of PTPases is mediated by elevated cAMP levels, most likely by activating phosphatase inhibitors.

Original languageEnglish (US)
Pages (from-to)E142-E149
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number2 25-2
StatePublished - 1992
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physiology (medical)
  • Physiology
  • Endocrinology, Diabetes and Metabolism


  • phosphoprotein phosphatases


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