Insulin regulation of pyruvate kinase activity in cultured rat hepatocytes, in the presence of vasopressin, ionophore A23187 or 4 beta-phorbol 12 beta-myristate 13 alpha-acetate.
The short-term interactions of insulin and vasopressin on pyruvate kinase (PK) activity were studied in primary cultures of rat hepatocytes. (1) Vasopressin inhibited PK activity by approx. 30% within 15 s, but activity returned to control values by 5 min. The transient inhibition by vasopressin was mimicked by either 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) or ionophore A23187. (2) Insulin alone transiently inhibited PK activity at 1 min, but stimulated PK activity at 5 and 15 min. (3) Insulin completely antagonized the early inhibition by vasopressin, PMA or A23187 of PK activity at 15 s. (4) Insulin inhibited PK activity in the presence of vasopressin, PMA or A23187 at 5 min. (5) 8-Bromo cyclic AMP inhibited PK activity within 15 s, and this inhibition was maintained for at least 5 min. Insulin did not antagonized the inhibition by the cyclic AMP analogue. These results show that insulin under appropriate conditions can act as an inhibitor or activator of PK.
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D011770:Pyruvate Kinase / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014667:Vasopressins / Q000494:pharmacology*
D007328:Insulin; D014667:Vasopressins; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000001:Calcimycin; D011770:Pyruvate Kinase; D013755:Tetradecanoylphorbol Acetate