Increased sensitivity of adipose tissue to insulin after in vivo treatment of yellow Avy/A obese mice with amino-terminal peptides of human growth hormone

Abstract

Treatment of obese yellow Avy/A mice with the human GH (hGH) peptide hGH-(1-43) enhanced the in vitro sensitivity of their adipose tissue to insulin. Insulin-stimulated glucose oxidation, as determined by measurement of 14CO2 production, was enhanced 106% after administration of hGH-(1-43) at a dosage of 1 microgram/day for 3 days. A significant increase in CO2 production was detected with as little as 100 ng peptide/day for 3 days. A single injection of 10 micrograms increased sensitivity to insulin 2-5 times. This enhancing effect of insulin action could not be seen in lean agouti A/a animals nor could it be demonstrated by in vitro addition of hGH-(1-43) to adipose tissue. Synthetic hGH-(1-43) was used for these studies, but initial physiological work was done with peptide isolated from pituitary glands. At equimolar doses, intact hGH, a trypsin digest of either hGH or BSA, carbidomethyl cysteine-hGH-(146-191), and hGH-(32-46) were inactive. Carbidomethyl cysteine-hGH-(1-139) and hGH-(1-15) showed the enhancing property, but were only about 10% as active as hGH-(1-43). HGH-(1-43) did not increase serum insulin concentrations in the obese mice. We conclude that when administered in vivo to obese mice, hGH-(1-43) enhances the sensitivity of adipose tissue to the action of insulin, an indication that the peptide may play a role in carbohydrate metabolism.