Insulin clearance and microsomal glutathione-insulin transhydrogenase in perfused livers of fed and fasted rats.
Clearance of exogenous insulin measured in perfused livers from rats fed ad lib or fasted X 24 or X 48 h was correlated with changes in activity and distribution of the insulin-degrading enzyme glutathione-insulin transhydrogenase measured in microsome fractions, post-perfusion. For comparison with endogenous insulin removal (Endocr. Res. Commun. 7: 231, 1980), a single-pass perfusion mode was used and clearance of insulin at levels (less than or equal to 15 ng/ml) typically observed in perfused rat liver-pancreases during glucose stimulation was studied. Similar to the endogenous data, exogenous insulin removal followed an ogival pattern during fasting. In the fed state, clearance was relatively low, corresponding to a hepatic extraction of approximately 29%. Insulin extraction increased nearly 2-fold after a 24 h fast to approximately 48% (p less than .01), declining to approximately 30% (p less than .025) when fasting was prolonged (X 48 h). At portal insulin concentrations greater than 8 ng/ml (approximately 200 microUnits/ml), clearance tended to decrease in all 3 nutritional states, with apparent saturation of the insulin capturing mechanism being strongest in the 24 h fasted state. In conjunction with these changes in whole organ insulin removal, GSH-insulin transhydrogenase nonlatency, viz., nonlatent activity in intact microsomes relative to total activity in disrupted microsomes, did not change during the first 24 h of fasting; whereas the proportion of nonlatent activity was significantly decreased (p less than .01) after 48 h. Homogenate activity remained essentially constant during the initial fasting period, and declined by approximately 16% (p less than .01) after 48 h of fasting.(ABSTRACT TRUNCATED AT 250 WORDS)
Striffler
J S
JS
Department of Biological Chemistry School of Medicine, Wright State University, Dayton, Ohio 45425.
D000818:Animals; D005215:Fasting; D005502:Food; D007328:Insulin / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D010088:Oxidoreductases / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism; D011490:Protein Disulfide Reductase (Glutathione) / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D010088:Oxidoreductases; D011490:Protein Disulfide Reductase (Glutathione); D010741:Phospholipases A