Nutrition and somatomedin. X. Comparison of insulin-like activity of somatomedins extracted from liver and serum

Uncontrolled diabetes in rats is associated with reduced levels of both serum somatomedins and hepatic somatomedins. Hepatic somatomedins are recognized after extraction with 5 mol/L acetic acid, have a higher molecular weight (about 30,000) than serum somatomedins (about 8,000), despite acid conditions that dissociate somatomedins from circulating carrier proteins, and stimulate cartilage when given in vivo. To determine if hepatic somatomedins--as potential prohormones--have insulin-like activity comparable with serum somatomedins, their effects on rat epididymal adipose tissue were examined. Somatomedins were prepared from serum and liver extracts by gel filtration on Sephadex G-75, pH 2.4. In initial studies with fat pad segments, extracted hepatic somatomedins increased glucose oxidation only 64 +/- 11% above buffer (mean +/- SEM), while stimulation of 372 +/- 48% was provided by extracted serum somatomedins of comparable cartilage-stimulating potency (P less than 0.01, liver v serum). Further examination was performed with isolated adipocytes in a system sensitive to insulin at a concentration of 10 microU/mL (stimulation 100% above buffer). In dose-response studies measuring glucose oxidation, hepatic somatomedins had insulin-like activity of 16 microU/mL versus 55 microU/mL for serum somatomedins equipotent on cartilage (P less than 0.05); measuring glucose incorporation into total lipids, hepatic somatomedins had undetectable activity while serum somatomedins had activity of 28 microU/mL. It is concluded that hepatic somatomedins with potent cartilage-stimulating activity have greatly reduced insulin-like activity. The apparent dissociation in biologic activity of hepatic somatomedins suggests that while they may be prohormones, they may also represent a class of growth factors separate from the circulating somatomedins.