AJP - Endocrinology and Metabolism, Vol 250, Issue 5 530-E537, Copyright © 1986 by American Physiological Society
Insulin metabolism by liver, muscle, and kidneys from spontaneously diabetic rats
R. Rabkin, G. M. Reaven and C. E. Mondon
The in vivo metabolism of insulin is a complex process in which liver,
kidney, and muscle are major participants. In this study we evaluated the
effect of spontaneous hyperglycemic nonketoacidotic diabetes (DH) and
ketoacidotic diabetes (DKA) on insulin clearance and degradation by these
organs. Livers, hindlimbs, and kidneys from nondiabetic controls and DH and
DKA Bio-Breed rats were isolated and perfused with artificial media. Liver
clearance of immunoreactive insulin (ml/min) was significantly higher in DH
rats, 6.0 +/- 0.2, but significantly lower in DKA rats, 3.4 +/- 0.5,
compared with controls, 4.6 +/- 0.2. Acidosis alone induced by ammonium
chloride loading, did not impair liver insulin clearance (4.8 +/- 0.4
ml/min). Muscle responded differently to the diabetic state in that insulin
clearance was not altered by DH and DKA. Renal (organ) clearance of insulin
was significantly depressed in the DKA state when compared with controls
(0.52 +/- 0.04 and 0.75 +/- 0.07 ml X min-1 X g-1, respectively). This
could largely be explained by a lower glomerular filtration rate.
Fractional urinary insulin clearance was increased twofold above control
values in DH kidneys and fourfold in DKA kidneys, indicating that tubular
luminal absorption of insulin was impaired in both states. By contrast
contraluminal uptake (peritubular clearance) did not differ significantly
from controls. 125I-insulin degrading activity of the 100,000 g supernate
fraction from muscle homogenates was similar in the diabetic and control
groups. However in liver and kidney, degrading activity did not correspond
to whole organ insulin clearance in a consistent manner.(ABSTRACT TRUNCATED
AT 250 WORDS)
