The action of adenosine 3',5'-monophosphate (c-AMP) and N6, O2'-dibutyryl adenosine 3',5'-monophosphate (dc- AMP) was studied in isolated rat adipocytes using parameters of glucose oxidation and lipolysis. Whereas c-AMP stimulated the conversion of glucose-U-C-14 or glucose-1-C-14 to C-14-O2, dc-AMP inhibited C-14-O2 production below the baseline in each case. Both N6-monobutyryl adenosine 3',5'-monophosphate (N6 mbc-AMP) and O2'-monobutyryl-adenosine 3',5'-monophosphate (O2'-mbc-AMP) stimulated C-14-O2 production from glucose-U-C-14. Only N6-mbc-AMP, however, was significantly lipolytic. When glucose-6-C-14 was utilized as the substrate, both c-AMP and dc-AMP stimulated its conversion to C-14-O2.
Dibutyryl cyclic AMP antagonized the action of insulin and proinsulin on glucose-U-C-14 oxidation in the isolated fat cell by an apparent competitive mechanism. Paradoxically, insulin potentiated C-14-O2 production from glucose-6-C-14. in the presence of 1.0 mM dc-AMP. C-AMP exhibited no such response.
It is concluded that under the experimental conditions described, (1) c-AMP and dc-AMP exhibit divergent effects with regard to glucose oxidation; (2) by the use of glucose-U-C-14 and glucose-l-C-14, dc-AMP competitively inhibits the action of insulin or proinsulin on glucose oxidation; (3) insulin synergistically stimulates C-14-O2 production from glucose-6-C-14, in the presence of dc-AMP; and (4) both N6- and O2'-butyrate moieties are necessary for the inhibitory effect on glucose oxidation observed with dc-AMP.
