Daily Fasting Blood Glucose Rhythm in Male Mice: A Role of the Circadian Clock in the Liver

Dec 15, 2015Endocrinology

Daily Changes in Blood Sugar in Male Mice Linked to the Body Clock in the Liver

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Abstract

Fasting blood glucose (FBG) levels exhibit significant daily rhythms, peaking at the beginning of the dark phase.

FBG rhythms were observed in both normal and diabetic mice, indicating a potential link to the hepatic clock.
Light-phase restricted feeding altered the FBG rhythm phase more significantly in diabetic ob/ob mice compared to normal C57BL/6J mice.
The disruption of the hepatic clock gene Bmal1 resulted in the loss of rhythmicity in FBG and glucose transporter expression.
Octreotide treatment reduced plasma growth hormone levels but did not influence the expression of clock genes or the FBG rise in C57BL/6J mice.

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Fasting blood glucose (FBG) and hepatic glucose production are regulated according to a circadian rhythm. An early morning increase in FBG levels, which is pronounced among diabetic patients, is known as the dawn phenomenon. Although the intracellular circadian clock generates various molecular rhythms, whether the hepatic clock is involved in FBG rhythm remains unclear. To address this issue, we investigated the effects of phase shift and disruption of the hepatic clock on the FBG rhythm. In both C57BL/6J and diabetic ob/ob mice, FBG exhibited significant daily rhythms with a peak at the beginning of the dark phase. Light-phase restricted feeding altered the phase of FBG rhythm mildly in C57BL/6J mice and greatly in ob/ob mice, in concert with the phase shifts of mRNA expression rhythms of the clock and glucose production-related genes in the liver. Moreover, the rhythmicity of FBG and Glut2 expression was not detected in liver-specific Bmal1-deficient mice. Furthermore, treatment with octreotide suppressed the plasma growth hormone concentration but did not affect the hepatic mRNA expression of the clock genes or the rise in FBG during the latter half of the resting phase in C57BL/6J mice. These results suggest that the hepatic circadian clock plays a critical role in regulating the daily FBG rhythm, including the dawn phenomenon.

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Daily Fasting Blood Glucose Rhythm in Male Mice: A Role of the Circadian Clock in the Liver

Abstract

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