Glucagon and insulin binding to liver membranes in a partially nephrectomized uremic rat model

The Journal of Clinical Investigation
V Soman, P Felig

Abstract

To investigate the role of glucagon and insulin receptor binding in the glucagon hypersensitivity and insulin resistance which characterize the glucose intolerance of uremia, liver plasma membranes were prepared from control rats (blood urea nitrogen [BUN] 15+/-1 mg/100 ml, creatinine 0.7+/-0.2 mg/100 ml), and from 70% nephrectomized rats (BUN 30+/-2 mg/100 ml, creatinine 2.2+/-0.2 mg/100 ml), and from 90% nephrectomized rats (BUN 46+/-3 mg/100 ml, creatinine 4.20+/-0.7 mg/100 ml), 4 wk after surgery. As compared to controls, the 90% nephrectomized rats had significantly higher levels of plasma glucose (95+/-4 vs. 125+/-11 mg/100 ml), plasma insulin (28+/-9 vs. 52+/-11 muU/ml), and plasma glucagon (28+/-5 vs. 215+/-18 pg/ml). Similar, but less marked, elevations were observed in the 70% nephrectomized animals. In liver plasma membranes from nephrectomized rats, specific binding of (125)I-glucagon was increased by 80-120%. Furthermore, glucagon (2 muM)-stimulated adenylate cyclase activity in nephrectomized rats was twofold higher than in controls. In contrast, fluoridestimulated adenylate cyclase activity was similar in both groups of rats. In marked contrast to glucagon binding, specific binding of (125)I-insulin to liver memb...Continue Reading

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Citations

Oct 29, 1986·Biochimica Et Biophysica Acta·M BalageG Grizard
Nov 9, 1978·The New England Journal of Medicine·V SomanP Felig
Feb 1, 1981·The Journal of Clinical Investigation·R A DeFronzoJ Wahren
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