Hyperinsulinemia compensates for infection-induced impairment in net hepatic glucose uptake during TPN

In animals receiving total parenteral nutrition (TPN), infection impairs ne t hepatic glucose uptake (NHGU) by 40% and induces mild hyperinsulinemia. I n the normal animal, the majority of the glucose taken up by the liver is d iverted to lactate, but in the infected state, lactate release is curtailed . Because of the hyperinsulinemia and reduced NHGU, more glucose is utilize d by peripheral tissues. Our aims were to determine the role of infection-i nduced hyperinsulinemia in 1) limiting the fall in NHGU and hepatic lactate release and 2) increasing the proportion of glucose disposed of by periphe ral tissues. Chronically catheterized dogs received TPN for 5 days via the inferior vena cava. On day 3, a fibrin clot with a nonlethal dose of E. col i was placed into the peritoneal cavity; sham dogs received a sterile clot. On day 5, somatostatin was infused to prevent endogenous pancreatic hormon e secretion, and insulin and glucagon were replaced at rates matching incom ing hormone concentrations observed previously in sham or infected dogs. Th e TPN-derived glucose infusion was adjusted to maintain a constant arterial plasma glucose level of similar to 120 mg/dl. after a basal blood sampling period, the insulin infusion rate was either maintained constant (infected time control, Hi-Ins, n = 6; sham time control, Sham, n 5 6) or decreased (infected 1 reduced insulin, Lo-Ins; n = 6) for 180 min to levels seen in n oninfected dogs (from 23 +/- 2 to 12 +/- 1 mu U/ml). Reduction of insulin t o noninfected levels decreased NHGU by 1.4 +/- 0.5 mg.kg(-1).min(-1) (P < 0 .05) and nonhepatic glucose utilization by 4.8 +/- 0.8 mg.kg(-1).min(-1) (P < 0.01). The fall in NHGU was caused by a decline in HGU (Delta-0.6 +/- 0. 4 mg.kg(-1).min(-1)) and a concomitant increase in hepatic glucose producti on (HGP, Delta 0.8 +/- 0.5 mg.kg(-1).min(-1)); net hepatic lactate release was not altered. Hyperinsulinemia that accompanies infection 1) primarily d iverts glucose carbon to peripheral tissues, 2) limits the fall in NHGU by enhancing HGU and suppressing HGP, and 3) does not enhance hepatic lactate release, thus favoring hepatic glucose storage. Compensatory hyperinsulinem ia plays a critical role in facilitating hepatic and peripheral glucose dis posal during an infection.