Acute changes in pancreatic insulin secretion and hepatic glucose kinetics in endotoxemic miniature pigs.
We have proposed a misinformed B-cell hypothesis to describe the effects of increased glucose flux across the pancreatic B cell early in endotoxemia, whereby those cells might misinterpret the true glycemic state and thus induce increased insulin release. This hypothesis was supported by the observations that [6-3H]glucose-derived rates of glucose disappearance increased before systemic hyperinsulinemia appeared in endotoxemic Yucatan miniature pigs. Reevaluation of this hypothesis later showed that pancreatic insulin secretion increased before any changes in systemic glucose disappearance or insulin concentrations and, because of significant increases in hepatic insulin extraction, may have led to some local effects of insulin on hepatic carbohydrate metabolism. The present study was conducted with more frequent sampling periods early during endotoxemia to further characterize the effects of this initial acute increase in pancreatic insulin secretion on hepatic glucose uptake, concomitant to net hepatic glucose production, as well as to further clarify the temporal relationships between pancreatic insulin release and the onset of hypoglycemia. We found that an increase in pancreatic insulin secretion is, indeed, the first event to occur, 30 minutes after initiation of endotoxin infusion, coincidental to the onset of significant decreases in portal and hepatic venous blood flow. [3(3)H]Glucose-derived rate of glucose disappearance first increased significantly at 60 minutes, and net hepatic glucose output increased significantly after 80 minutes of endotoxin infusion. Net [3(-3)H]glucose uptake by the liver occurred through 50 minutes of endotoxin infusion. After this, there was a significant reversal in transhepatic isotope kinetics, resulting in net release of [3(-3)H]glucose from the liver for the duration of endotoxin infusion (140 minutes).(ABSTRACT TRUNCATED AT 250 WORDS)
Fettman
M J
MJ
Hand
M S
MS
Van Order
P
P
Phillips
R W
RW
D000818:Animals; D004731:Endotoxins / Q000097:blood*; D004926:Escherichia coli; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008102:Liver Circulation; D013552:Swine; D013556:Swine, Miniature / Q000502:physiology*
D004731:Endotoxins; D007328:Insulin; D005947:Glucose