Date of Award

1986

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Abstract

Lipogenic responsiveness to insulin was investigated at different times of day in freshly isolated hepatocytes and in primary cultured hepatocytes of Syrian hamsters, Mesocricetus auratus held on 14 hour daily photoperiods (lights on: 08.00) by following (('14)C)acetate incorporation into total cell lipid. The influence of prolactin on lipogenesis was tested by adding the hormone in vivo and directly to primary cultured hepatocytes. The findings of these studies are unique in that they demonstrate important roles of temporal interaction between prolactin and insulin in regulation of lipogenesis in cultured hepatocytes. They are summarized as follows: (1) A circadian variation of lipogenesis and lipogenic responsiveness to insulin exists in freshly isolated hepatocytes with maximum lipogenic activity occurring when the cells were isolated from animals during the late dark period of the day (0700). (2) A circadian variation in insulin receptor number exists (3-fold greater at 0700 than at 1600) that coincides directly with the variation in lipogenic response to insulin in freshly isolated hepatocytes. (3) Inhibition of lipogenesis and lipogenic responsiveness to insulin in freshly isolated hepatocytes is induced by bromocriptine (an inhibitor of prolactin secretion) pretreatment in vivo and both activities can be restored by concurrent prolactin injections. (4) A 70% decrease of insulin receptor number at the time of peak lipogenic responsiveness to insulin (0700) in freshly isolated hepatocytes is induced by bromocriptine pretreatment in vivo and restored to control levels by concurrent prolactin injections. (5) A circadian rhythm of lipogenic responsiveness to insulin persists for at least 2 days in primary cultured hepatocytes. (6) A circadian rhythm of lipogenic responsiveness to prolactin exists in primary cultured hepatocytes.

Pages

59

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