title: Role of cAMP in mediating effects of fasting on dephosphorylation of insulin receptor.
abstract: 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 microM 12-O-tetradecanoylphorbol-13-acetate) nor inhibition (20 microM 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 micrograms/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.
authors.affiliation: Department of Medicine, Veterans Administration Medical Center, Denver, Colorado.
authors.forename: N
authors.initials: N
authors.lastname: Begum
authors.forename: A L
authors.initials: AL
authors.lastname: Graham
authors.forename: K E
authors.initials: KE
authors.lastname: Sussman
authors.forename: B
authors.initials: B
authors.lastname: Draznin
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000201:enzymology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D005215:Fasting; D005947:Glucose / Q000494:pharmacology; D008297:Male; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D003994:Bucladesine; D000242:Cyclic AMP; D011972:Receptor, Insulin; D017027:Protein Tyrosine Phosphatases; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate