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Hepatic Proliferative Response to Insulin in Severe Alloxan Diabetes¹

Department of Biochemistry, University of Chicago, Chicago, Illinois

Administration of insulin to severely diabetic rats leads to marked proliferation of liver cells. The activity of DNA polymerase and the incorporation of thymidine-³H into hepatic DNA in vivo are increased within 24 hr after insulin injections are started and reach peak levels between 48 and 72 hr. Total liver DNA increases approximately 70% during the period from 36 to 72 hr of insulin treatment. The increase in DNA is accompanied by cell division rather than being due to an increase in ploidy, and is comparable in magnitude to the proliferation of liver cells which follows surgical removal of between 43 and 68% of the liver. Hypophysectomy reduces but does not prevent cell proliferation in response to insulin. The relationship of this response to the regulation of hepatic biosynthetic activities by insulin is discussed.

¹ Supported by Grant AM-04931, USPHS, and by the Lolly Coustan Memorial Fund, Chicago, Illinois.

² Present address: Beth Israel Hospital, Boston Massachusetts.

³ Holder of a Career Development Award of the USPHS.

Received 12/ 3/65.