Persistent hyperinsulinemia due to induced euglycemia in awake endotoxic minipigs.
Transient hyperinsulinemia has been incriminated as a contributing factor to endotoxin-induced hypoglycemia. However, a recent study using endotoxic minipigs noted an increase in the rate of glucose utilization prior to when hyperinsulinemia was seen. Based on this, the "misinformed beta-cell" hypothesis was proposed. If endotoxic pancreatic beta-cells experience an early increase in glucose uptake, they could over-estimate the true glycemic state and release insulin, further contributing to the hypoglycemia. Hypoglycemia would offset increased glucose uptake by the beta-cell and insulin secretion would return to basal rates, explaining the transient nature of the insulin response. According to this hypothesis, maintenance of euglycemia should elicit a sustained rather than transient insulin release. The hypothesis was tested with a euglycemic clamp technique in a group of five endotoxic (Difco 055:B5; 15 micrograms/kg/hr) minipigs (EC) compared to three nonclamped endotoxic minipigs (E). Persistent, profound hyperinsulinemia (15 ng/ml) occurred in the EC group, further supporting the hypothesis. The clamp appeared to be beneficial, since arterial pressure and pH were significantly (P less than or equal to 0.05) higher and arterial lactate levels were lower in EC pigs compared to E pigs. A significant discrepancy was noted between the radioisotope ( [6-3H] glucose)-derived rate of glucose appearance and the rate of exogenous glucose infusion (clamp), which may have been due to unaccounted for changes in glucose pool size and/or futile cycling of glucogenic substrates or glucose through glycogen and lipid.
D000136:Acid-Base Equilibrium; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure; D001798:Blood Proteins / Q000378:metabolism; D004731:Endotoxins / Q000097:blood*; D004926:Escherichia coli; D005260:Female; D006946:Hyperinsulinism / Q000097:blood*; D007328:Insulin / Q000097:blood; D007700:Kinetics; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008297:Male; D012772:Shock, Septic / Q000097:blood*; D013552:Swine; D013556:Swine, Miniature
D001786:Blood Glucose; D001798:Blood Proteins; D004731:Endotoxins; D007328:Insulin; D007773:Lactates; D019344:Lactic Acid