CHRONIC AND TRANSITIONAL REGULATION OF GLUCONEOGENESIS AND GLYCONEOGENESIS BY INSULIN AND GLUCAGON IN NEONATAL CALF HEPATOCYTES

Milk-fed calves were used as a source of hepatocytes to establish monl ayers to test the effects of chronic (41 h) incubation with no hormone , 100 nM insulin, or 100 nM glucagon on gluconeogenesis (glucose retai ned as glycogen plus glucose released into the medium) from 2.5 nM [2- C-14]propionate and 2.0 mM [U-(14C)]lactate ( 1.0 nM lactate plus 1.0 mM pyruvate) during a subsequent 3-h (acute) incubation. Media for acu te incubations contained no hormone, 0 or 10 nM insulin, or 0, 1, 10, or 100 mM glucagon. Chronic glucagon increased gluconeogenesis from pr opionate and glyconeogenesis from propionate and lactate compared with chronic exposure to medium with no hormone, A chronic glucagon x acut e hormone interaction was manifested as an augmented response to acute glucagon on gluconeogenesis from propionate; a similar potentiation w as not evident for gluconeogenesis from lactate. The concentration of glucagon required to acutely stimulate gluconeogenesis was increased b y prior incubation with glucagon. Acute glucagon decreased the flux of glucose retained as glycogen regardless of chronic hormone treatment, Chronic incubation with insulin diminished the stimulatory effects of glucagon on gluconeogenesis from lactate. Chronic incubation with ins ulin did not alter the sensitivity or responsiveness at acute glucagon of gluconeogenesis from propionate. The data demonstrate persisting c hanges that favor increased basal gluconeogenesis from propionate with chronically elevated glucagon coupled to an increased capacity to res pond acutely to glucagon and opposing chronic actions of insulin on la ctate metabolism. These data suggest that insulin and glucagon target separate pathways that are unique to metabolism of propionate and lact ate.