Hyperglycemic activity of the 20,000-dalton variant of human growth hormone

The 20,000-dalton structural variant of human growth hormone was inactive as a hyperglycemic agent in dogs when injected 10 h prior to a glucose tolerance test. Limited digestion with subtilisin did not generate hyperglycemic activity. These results are in contrast to those obtained with human growth hormone where subtilisin treatment potentiated the weak hyperglycemic activity of the undigested hormone. The results suggest that the 15 amino acid sequence that is deleted from the variant is either directly responsible for hyperglycemic activity or that a modification in tertiary structure produced by the deletion prevents a necessary proteolytic processing.