Effect of Exogenous Glucagon and Free Fatty Acids on Gluconeogenesis in Fasting Neonatal Pigs

Summary

Thirty-two pigs (1 d old) were used to determine if exogenous glucagon and(or) free fatty acids (FFA oleic acid) would enhance gluconeogenesis and glucose homeostasis during fasting. Pigs were acquired at birth, fitted with an indwelling arterial cannula (via umbilicus) and fasted 24 h to deplete liver glycogen. A jugular cannula was inserted nonsurgically 8 to 10 h before initiation of a primed-continuous infusion consisting of control (excipient), glucagon (Glu), oleic acid (FFA), or both glucagon and oleic acid (Glu-FFA). Plasma Glu averaged 395 pg/ml preinfusion and was similar across treatments. The concentration increased fivefold (P<.05) by 80 min for Glu and Glu-FFA pigs and remained constant thereafter (160 min: 2,379, 2,258 pg/ml; 240 min: 2,355, 2,274 pg/ml, respectively). Glucagon infusion did not alter plasma glucose after 240 min of infusion (control, 50 vs Glu, 51 mg/dl); however, Glu-FFA effected an increase (60 mg/dl, P<.10). In contrast, pigs infused with FFA alone had a lower glucose concentration (40 mg/dl, P<.10). Rate of glucose synthesis was determined using liver slices, acquired immediately postinfusion, with alanine and lactate as substrate (7.5 mM). The rate of synthesis was not altered by Glu or Glu-FFA infusion (2.91, 2.43 μmol glu cose•g⁻¹•h⁻¹ vs 2.91 for control). In contrast, exogenous FFA reduced synthesis to 1.85 μmol glucose•g⁻¹•h⁻¹ (P<.05) with lactate as substrate. It appears that Glu is not the primary factor limiting gluconeogenesis in fasting newborn pigs. Simultaneous infusion of Glu and FFA may have improved plasma glucose status by altering glucose turnover via Glu-mediated fatty acid oxidation.

Neonatal Pig, Hypoglycemia, Glucagon, Gluconeogenesis, Free Fatty Acids

© American Society of Animal Science 1985