“…Increases in cAMP, such as occur during times of metabolic stress when circulating glucagon levels are high, protect cultured hepatocytes from apoptosis due to several stimuli including bile acids, Fas, and TNF-␣ (12,21,36,61). In vivo, oral administration of phosphodiesterase inhibitors (18,32) or  2 -adrenergic agonists (1), agents that increase hepatic cAMP levels, or parenteral administration of glucagon (24) or cell-permeable cAMP analogs (28,57) protect against toxic and ischemic hepatic injury in laboratory animals. Furthermore, it is known that the diseased liver develops dysregulations in cAMP signaling that contribute to increased hepatobiliary damage (15,19,20,27,35).…”