Non-insulin-mediated glucose uptake in fed and fasted sheep

Abstract

AbstractIn ruminants and humans, the majority of whole body glucose utilization is not mediated by insulin. However, while in man most non-insulin-mediated glucose utilization (NIMGU) occurs in the brain, in ruminants the locations of NIMGU remain less well defined. As fasting would be expected to limit NIMGU to what would be regarded as an essential minimum, two studies were performed to establish the contribution of NIMGU to total glucose metabolism in fed and fasted sheep. Each study used four adult castrated male sheep. In study 1, a primed continuous infusion of U- [13C] glucose was begun at time 0 and continued for 7 h. After 3 h of isotope infusion (basal period) somatostatin (0•417 µg/kg per min; SS) was administered for 4 h, either alone (SS-only) or together with insulin (1•0 mU/kg per min; SS + insulin) with normal glucose to maintain euglycaemia for 2 h. Normal glucose was then infused for both the SS-only and SS + insulin treatments to induce and maintain hyperglycaemia over the final 2 h of the experiment. In study 2, fed or 72-h fasted sheep were infused with 6-[3H] glucose from time 0 for 8 h, with SS infusion starting at 3 h and continuing for 5 h. After 3 h of SS infusion, glucose was infused to induce and maintain hyperglycaemia. In both studies SS infusion inhibited insulin secretion, however in study 2, SS in fed sheep caused hyperglycaemia; this effect was not significant in the fasted animals. The rate of glucose utilization was reduced by SS-only as it eliminated insulin mediated glucose uptake (IMGU); under such conditions whole body glucose disposal should be NIMGU. In fed sheep, average NIMGU levels represented between proportionately 0•61 and 0•67 of the basal glucose metabolic clearance rate. During the infusion of SS + insulin in fed sheep, NIMGU fell to 0•34 during euglycaemia and 0•33 during hyperglycaemia, as the infused insulin caused IMGU to predominate. In fasted sheep the absolute rates of both IMGU and NIMGU were reduced, though NIMGU as a proportion of total turn-over (IMGU + NIMGU) increased to 0•88 of glucose metabolic clearance. Calculations suggest that, in contrast to man, only a minor proportion of NIMGU is utilized by the brain and central nervous system in fed or fasted sheep. It is suggested that skeletal muscle and the gastro-intestinal tract may make a major contribution to NIMGU, even in fasted sheep.