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 monlayers to test the effects of chronic (41 h) incubation with no hormone, 100 nM insulin, or 100 nM glucagon on gluconeogenesis (glucose retained as glycogen plus glucose released into the medium) from 2.5 mM [2-(14)C]propionate and 2.0 mM [U-14C]lactate (1.0 mM lactate plus 1.0 mM pyruvate) during a subsequent 3-h (acute) incubation. Media for acute incubations contained no hormone, 0 or 10 nM insulin, or 0, 1, 10, or 100 mM glucagon. Chronic glucagon increased gluconeogenesis from propionate and glyconeogenesis from propionate and lactate compared with chronic exposure to medium with no hormone. A chronic glucagon x acute hormone interaction was manifested as an augmented response to acute glucagon on gluconeogenesis from propionate; a similar potentiation was not evident for gluconeogenesis from lactate. The concentration of glucagon required to acutely stimulate gluconeogenesis was increased by 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 insulin did not alter the sensitivity or responsiveness at acute glucagon of gluconeogenesis from propionate. The data demonstrate persisting changes that favor increased basal gluconeogenesis from propionate with chronically elevated glucagon coupled to an increased capacity to respond acutely to glucagon and opposing chronic actions of insulin on lactate metabolism. These data suggest that insulin and glucagon target separate pathways that are unique to metabolism of propionate and lactate.
Donkin
S S
SS
Department of Dairy Science, University of Wisconsin, Madison 53706, USA.
Bertics
S J
SJ
Armentano
L E
LE
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002417:Cattle / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005934:Glucagon / Q000494:pharmacology*; D005943:Gluconeogenesis / Q000187:drug effects* / Q000502:physiology; D006003:Glycogen / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D007773:Lactates / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D011422:Propionates / Q000378:metabolism; D013997:Time Factors
D002250:Carbon Radioisotopes; D007328:Insulin; D007773:Lactates; D011422:Propionates; D006003:Glycogen; D005934:Glucagon