Hagedorn and his co-workers1 have prepared from the sperm of a trout (Salmo iridius) the substance protamine, which, properly buffered, combines with insulin to form the compound protamine insulinate or, for want of a less confusing name, "protamine insulin." When this compound, which is sparingly soluble in the tissue fluid, is given hypodermically, it slowly breaks down so that the active insulin is gradually released and absorbed, thereby causing a continuous and prolonged action on the blood sugar.
It has been reported that occasionally the final effectiveness of protamine is delayed beyond the day of its administration as late as four or five days.2 The duration of this prolonged absorption appears to approach nature's method of continuous insulin secretion. The Hagedorn investigators, basing their conclusions on a carefully treated group of diabetic patients, have shown these encouraging results with protamine insulin: a more prolonged insulin action without increasing
SINDONI A. PROTAMINE INSULIN VERSUS ORDINARY INSULIN. JAMA. 1937;108(16):1320–1327. doi:10.1001/jama.1937.02780160012004
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