Studies on the biological activity of porcine proinsulin

Norman R. Lazarus; Juan C. Penhos; Tomio Tanese; Leslie Michaels; Raul Gutman; Lillian Recant

doi:10.1172/JCI106258

^{Diabetes Research Laboratory, Veterans Administration Hospital, Washington, D. C. 20422}

^{Georgetown University, Washington, D. C. 20007}

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^{Diabetes Research Laboratory, Veterans Administration Hospital, Washington, D. C. 20422}

^{Georgetown University, Washington, D. C. 20007}

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^{Diabetes Research Laboratory, Veterans Administration Hospital, Washington, D. C. 20422}

^{Georgetown University, Washington, D. C. 20007}

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^{Diabetes Research Laboratory, Veterans Administration Hospital, Washington, D. C. 20422}

^{Georgetown University, Washington, D. C. 20007}

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^{Diabetes Research Laboratory, Veterans Administration Hospital, Washington, D. C. 20422}

^{Georgetown University, Washington, D. C. 20007}

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^{Diabetes Research Laboratory, Veterans Administration Hospital, Washington, D. C. 20422}

^{Georgetown University, Washington, D. C. 20007}

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Published in Volume 49, Issue 3 on March 1, 1970
J Clin Invest. 1970;49(3):487–496. https://doi.org/10.1172/JCI106258.
© 1970 The American Society for Clinical Investigation

Published March 1, 1970 - Version history

The biological activity of purified porcine proinsulin was investigated in rats. In vivo studies revealed that proinsulin produced a hypoglycemic response similar to insulin but of lesser magnitude. Hypophysectomized and adrenalectomized animals proved to be more sensitive to proinsulin than normal. In vitro studies with rat hemidiaphragm were consistent with the in vivo findings. No competition with insulin action could be demonstrated.

Experiments were carried out to determine whether proinsulin is converted to intermediate forms or insulin as a requisite to its biological activity. Labeled proinsulin injected in vivo or incubated in vitro remained intact by a variety of techniques (Sephadex column chromatography and polyacrylamide-gel electrophoresis).

An inhibitory action of Kunitz pancreatic trypsin inhibitor on proinsulin action in vitro was confirmed. No clarification of this effect could be ascertained.

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