Insulin Resistance and Diabetes Affected the Circadian-clock System

• Main Authors: Huey-Ling Tseng, 曾慧玲
• Other Authors: Kun-Ruey Shieh
• Format: Others
• Language: en_US
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/18979040116552107854

博士 === 慈濟大學 === 醫學科學研究所 === 102 === Circadian rhythm is the intrinsic rhythm which is in coordination with the rotation of the earth. Physiological and behavioral processes of many organisms such as sleep/wake cycles, body temperature, blood pressure, hormone production, feeding, and metabolism etc., have 24-hour rhythm. Circadian rhythm is also generated by a set of circadian-clock genes at the intracellular levels. These genes compose the transcriptional/translational feedback loops to regulate not only circadian rhythmicity but also energy metabolism. Previous studies have shown that obesity and diabetes mellitus (DM) cause the dysregulations of circadian-clock system, and vice versa; however, the rudimentary mechanisms remain unclear. In the present study, type 1 DM was induced by a single intraperitoneal injection of streptozotocin (STZ) in adult male Sprague-Dawley rats. A single injection of STZ into male C57BL/6 mice of two days old induced insulin resistance to type 2 DM. Gene expression levels of the hepatic circadian-clock system were examined by real-time quantitative PCR. We found that 1) the hepatic circadian-clock system was altered in type 1 diabetic rats, and treatment with insulin was able to partially rescue changes in the circadian-clock system; 2) changes of hepatic circadian-clock gene expression marked an early event in the metabolic disruption associated with insulin resistance. Furthermore, treatments for two weeks with the thiazolidinedione, rosiglitazone or pioglitazone, fully rescued the dysfunctions of metabolic parameters and the changes of circadian-clock gene expressions in the early insulin resistance conditions. Chronic administration of rosiglitazone was effective in the type 2 diabetic condition. Together, our results supported an essential role of the hepatic circadian-clock system in the coordinated control and regulation of metabolic pathways.