Insulin dissociates hepatic glucose cycling and glucagon-induced thermogenesis in man

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The quantitative contribution of hepatic glucose cycling to basal and glucagon-stimulated thermogenesis was investigated in seven normal healthy volunteers in whom energy expenditure (EE) was measured simultaneously with indirect calorimetry. Primed-constant infusions of 2-( 2H 1)-glucose and 6-6′-( 2H 2)-glucose were used to calculate hepatic glucose cycling. Gas chromatography/mass spectrometry was used to measure the plasma enrichment of isotopes. In response to hyperglucagonemia, basal EE increased an average of 7.1% ± 2.3% ( P < .05). This thermogenic effect of glucagon was completely blunted when insulin levels were increased sevenfold over the basal concentration. Hepatic glucose cycling comprised 15% ± 4% of basal glucose turnover and increased more than 100% in response to isolated hyperglucagonemia. The increase in liver glucose cycling was observed also when serum insulin concentrations were increased sevenfold above baseline. Thus, we were able to induce dissociation of the activation of hepatic glucose cycling and the thermogenic response induced by hyperglucagonemia. From the quantitative point of view, the thermogenic cost of the cycles was less than 1% in both the basal and stimulated state. Thus, we concluded that hepatic glucose cycles play a quantitatively minor role in EE in man.