Incubation of intact hepatocytes with either of the synthetic diacyl glyccrols I-oleoyl-2-acetyl glycerol (OAG) or dihexanoyl glycerol (DHG) caused the transient uncoupling of the ability of glucagon to stimulate adenylate cyclase in membranes prepared from those cells. No change occurred in either the activity of the catalytic unit of adenylate cyclase or the coupling of G, to adenylate cyclase. Diacyl glycerol action appeared to mimic glucagon-mediated desensitization of adenylate cyclase, suggesting that protein kinase C activation may provide the molecular trigger for glucagon desensitization.
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