Circadian Stage-Dependent Effects of Insulin and Glucagon on Incorporation of [3H]Thymidine into Deoxyribonucleic Acid in the Esophagus, Stomach, Duodenum, Jejunum, Ileum, Caecum, Colon, Rectum, and Spleen of the Adult Female Mouse*

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Abstract
Insulin and glucagon were injected ip at four different circadian stages into separate subgroups of female adult BALB/Cann mice that had been standardized to 12 h of light alternating with 12 h of darkness. Comparable control subgroups were injected with saline. Four, 8, 12, and 18 h after each of the four injections, subgroups of seven mice that had been injected 30 min earlier with tritiated thymidine ([3H]TdR) were killed; a total of 336 mice were used. The incorporation of [3H]TdR into DNA of the esophagus, stomach, duodenum, jejunum, caecum, colon, rectum, and spleen was subsequently determined. The results demonstrate for the first time that both hormones affect the incorporation of [3H]TdR into DNA in all of the examined organs but in different ways and at different circadian stages. The effects of these hormones were complex, but several generalizations emerged. 1) Insulin tended to increase the incorporation of [3H]TdR into DNA in the examined organs, whereas glucagon tended to decrease it. 2) Insulin was more effective in stimulating the incorporation of [3H]TdR into DNA when injected either at the end of the dark span or the beginning of the light span, as opposed to the end of the light span or the beginning of the dark span. 3) Insulin had its greatest effect on [3H]TdR incorporation into DNA in the glandular stomach and rectum, whereas glucagon had its greatest effect on the colon and spleen. 4) The effects of both insulin and glucagon were different from those of epidermal growth factor, as revealed in a similar study done by us. Our results suggest that insulin, glucagon, and epidermal growth factor play important roles in the control of growth of various endodermally derived organs.