Regulation of free fatty acid metabolism by glucagon
MG Carlson, WL Snead and PJ Campbell
Department of Medicine, Vanderbilt University School of Medicine, Nashville 37232-2230.
Glucagon may regulate FFA metabolism in vivo. To test this hypothesis, six
healthy male volunteers were infused with somatostatin, to inhibit
endogenous hormone secretion, and insulin, glucagon, and GH to replace
endogenous secretion of these hormones. In the hypoglucagonemia
experiments, the glucagon infusion was omitted, and in the
hyperglucagonemic experiments glucagon was infused at 1.3 ng/kg.min, to
produce physiological hyperglucagonemia. In two sets of control
experiments, glucagon was infused at 0.65 ng/kg.min, in order to maintain
peripheral euglucagonemia, and the plasma glucose concentrations were
clamped at the levels observed in either the hypo- or hyperglucagonemic
experiments. Rates of FFA and glycerol (an index of lipolysis) appearance
(Ra) were estimated with the isotope dilution method using [1-14C]palmitate
and [2H5] glycerol. Plasma glucagon concentrations decreased during the
hypoglucagonemic experiments (85 +/- 12 vs. 123 +/- 22 ng/L, P < 0.05)
and increased during the hyperglucagonemic experiments (186 +/- 20 vs. 125
+/- 15 ng/L, P < 0.05), whereas other hormone concentrations remained
the same. Hypoglucagonemia resulted in equivalent suppression of FFA Ra
(3.7 +/- 0.2 vs. 5.9 vs. 0.3 mumol/kg.min, P < 0.01) and glycerol Ra
(1.2 +/- 0.2 vs. 2.2 +/- 0.5 mumol/kg.min, P < 0.05). Similarly,
hyperglucagonemia resulted in equivalent stimulation of FFA Ra (5.2 +/- 0.4
vs. 3.7 +/- 0.3 mumol/kg.min, P < 0.05) and glycerol Ra (1.5 +/- 0.3 vs.
1.1 +/- 0.1 mumol/kg.min, P < 0.05). These results indicate that
glucagon has a physiological role in the regulation of FFA metabolism in
vivo.
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