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Effect of Exogenous Glucagon and Free Fatty Acids on Gluconeogenesis in Fasting Neonatal Pigs^1,2,

Cornell University⁴, Ithaca, NY 14853-0281

Abstract

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 glucose·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.

¹ Supported by the Cornell Univ. Agr. Exp. Sta. and National Pork Producers Council. Portions of this paper were presented at the 75th Annu. Meet. of the Amer. Soc. of Anim. Sci. in Pullman, WA, 1983, abstract no. 137.

² The authors gratefully acknowledge the assistance of Dr. D. E. Bauman for suggestions on design and experimental procedure. Likewise, the authors wish to express appreciation to Drs. D. Anderson and Mary Root of the Eli Lilly Co. for supplying glucagon and insulin and to Priscilla Lawrence for typing this manuscript.

³ To whom reprint requests should be directed.

⁴ Dept. of Anim. Sci.