内分泌学と糖尿病の研究

Distinct Changes in Adipose Tissue and Muscle in Response to Excess Systemic Glucose in Rats

X Julia Xu1, Amanda E Brandon, Ella Stuart, Kaajal Patel1, Reyhan Gedik1, Asish Saha1, Edward W Kraegen and Neil B Ruderman1

Objective: Excess nutrients can cause insulin resistance in skeletal muscle in vivo. However, the response of white adipose tissue is less clear. In a chronic glucose infusion model (1 and 4 days), distinct adaptations in muscle and white adipose tissue have been described. Muscle developed sustained insulin resistance after 1 day of glucose infusion but adipose tissue did not. Exactly what distinguishes adipose tissue from muscle in response to glucose oversupply remains to be determined. The aim of the present study was to investigate the early (3-8 h) metabolic and signaling changes that take place in epididymal fat pads, and to a lesser extent, red quadriceps muscle, using an acute glucose infusion model.
Methods: Hyperglycemia (~11 mM) and hyperinsulinemia were generated by infusing glucose into rats for 3, 5, or 8 h.
Results: We found that similar to red quadriceps muscle, AMPactivated protein kinase (AMPK) activity was diminished in epididymal fat pads of the glucose infused rats. Yet, both glucose uptake and triglyceride synthesis were increased in epididymal fat whereas muscle showed a progressive decrease in glucose utilization and glycogen synthesis after 5 h. Insulin signaling, as determined by Akt phosphorylation (Ser473), remained intact in epididymal fat but not in red quadriceps muscle. Furthermore, unlike muscle, there was no evidence of PKC activation in epididymal fat.
Conclusion: The results confirmed and extend findings that suggest white adipose tissue responds very differently than muscle when exposed to sustained elevated concentration of glucose.