Many biological systems are regulated by an intricate set of feedback loops that oscillate with a circadian rhythm of roughly 24 h. This circadian clock mediates an increase in body temperature, heart rate, blood pressure, and cortisol secretion early in the day. Recent studies have shown changes in the amplitude of the circadian clock in the hearts and livers of streptozotocin (STZ)-treated rats. It is therefore important to examine the relationships between circadian clock genes and growth factors and their effects on diabetic phenomena in animal models as well as in human patients. In this study, we sought to determine whether diurnal variation in organ development and the regulation of metabolism, including growth and development during the juvenile period in rats, exists as a mechanism for anticipating and responding to the environment. Also, we examined the relationship between changes in growth factor expression in the liver and clock-controlled protein synthesis and turnover, which are important in cellular growth. Specifically, we assessed the expression patterns of several clock genes, including Per1, Per2, Clock, Bmal1, Cry1 and Cry2 and growth factors such as insulin-like growth factor (IGF)-1 and -2 and transforming growth factor (TGF)-β1 in rats with STZ-induced diabetes. Growth factor and clock gene expression in the liver at 1 week post-induction was clearly increased compared to the level in control rats. In contrast, the expression patterns of the genes were similar to those observed after 5 weeks in the STZ-treated rats. The increase in gene expression is likely a compensatory change in response to the obstruction of insulin function during the initial phase of induction. However, as the period of induction was extended, the expression of the compensatory genes decreased to the control level. This is likely the result of decreased insulin secretion due to the destruction of beta cells in the pancreas by STZ.

ABSTRACT   INTRODUCTION   MATERIALS AND METHODS    Animals and Induction of Diabetes    Experimental Design    RNA Extraction and RT-PCR    Statistical Analysis   RESULTS    Blood Glucose Levels    Growth Factor Gene Expression   DISCUSSION   REFERENCES

• Joo-Heon Kim(Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University)
• Cheol-Soo Shim(Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University)
• Jinyoung Won(Department of Physical Therapy, College of Biomedical Science & Engineering, Inje University)
• Youngji Park(Department of Physical Therapy, College of Biomedical Science & Engineering, Inje University)
• Sookyoung Park(Department of Physical Therapy, College of Biomedical Science & Engineering, Inje University)
• Jae Seon Kang(Department of Pharmacy, Kyungsung University)
• Yonggeun Hong(Department of Physical Therapy, College of Biomedical Science & Engineering, Inje University) Corresponding author