AJP - Endocrinology and Metabolism, Vol 252, Issue 2 E209-E217, Copyright © 1987 by American Physiological Society
First-pass hepatic extraction and metabolic effects of insulin and insulin analogues
Z. Chap, T. Ishida, J. Chou, C. J. Hartley, M. L. Entman, D. Brandenburg, R. H. Jones and J. B. Field
First-pass hepatic extraction of insulin and hepatic and peripheral
contributions to hypoglycemia were compared in conscious dogs during portal
infusion of insulin A1, B29 diacetyl insulin, or A1-B29 dodecoyl insulin at
7 and 14 pmol X kg-1 X min-1. The liver removed 43 +/- 2% of insulin, 12
+/- 1% of dodecoyl, and 8 +/- 1% of diacetyl insulin, in a single
transhepatic circulation. The hypoglycemia induced by insulin and diacetyl
insulin and the ensuing glucagon response were greater than that produced
by the dodecoyl analogue. Diacetyl insulin primarily increased glucose
utilization, dodecoyl insulin solely inhibited hepatic production, and
insulin affected both. The lack of hepatic effect of diacetyl insulin
during hypoglycemia can be ascribed to greater counterregulation, because
under euglycemic clamp conditions, this analogue caused suppression of
glucose production. The different patterns of hypoglycemia exhibited can be
explained by the combined effects of altered distribution between the liver
and peripheral tissues caused by differences in hepatic extraction, the
effect of this phenomenon on the counterregulatory response, and the
intrinsic biological potency of the analogues.
