Glucagon has recently been shown to have a direct lipolytic action on liver (Bewsher and Ashmore 1966). Increased hepatic lipolysis, plus enhanced availability of plasma fatty acids, causes an elevation of acetyl CoA and fatty acyl CoA levels (Williamson, Herczeg, Coles and Danish 1966). Such elevated levels of acetyl CoA presumably account for the increased rate of ketogenesis observed with glucagon.

Acute effects of insulin deficiency, induced by administration of guinea pig anti-insulin serum (AIS) to rats, are similar to effects produced by glucagon: elevation of plasma glucose, free fatty acid, and ketone levels, plus an increased rate of gluconeogenesis (Wagle and Ashmore, 1963; Wagle and Ashmore, 1964; Tarrant, Mahler, and Ashmore, 1964). These findings have led to the suggestion that the early metabolic changes in experimental insulin deficiency may be induced by hormones with actions normally counterbalanced by insulin (Wright, 1965). Such hormones are glucagon, epinephrine, ACTH and corticosteroids (Mahler, Stafford, Tarrant and Ashmore, 1964; Jungas and Ball, 1963).

Data presented in this paper supports the concept that the lipolytic, ketogenic, and gluconeogenic effects of glucagon are revealed in the insulin-deficient rat. It is suggested that stimulation of gluconeogenesis, both with glucagon and with AIS, is secondary to enhanced lipolysis and is mediated through facilitation of pyruvic carboxylase by elevated hepatic levels of acetyl CoA.