Gender difference in glucose utilization of skeletal muscle during early-phase sepsis

• Main Authors: Yi Wen Lin, 林怡彣
• Other Authors: J. K. Chen
• Format: Others
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/03635835120626691847

碩士 === 長庚大學 === 生物醫學研究所 === 97 === The initial abnormality of glucose metabolic response during sepsis can be affected by the counter-regulatory hormones (i.e., catecholamines and cortisol) increase. Hyperglycemia and insulin resistance in skeletal muscle occurred. Studies have shown that sepsis-induced stress hyperglycemia is an important risk marker of morbidity and mortality. Estradiol (E2) plays a protective role in sepsis and it regulates insulin actions and maintains glucose homeostasis. We had also found that the survival rate of females is better than males during sepsis. Sepsis was induced in Sprague-Dawley rats of both genders by cecal ligation and puncture (CLP). We found that CLP-induced hyperglycemia in all animals at 3 hours later and it was severer in males than females. E2 administration (10mg/kg, i.p.) reduced the level of blood glucose. In order to investigate the mechanisms of hyperglycemia and potential effects of E2, we than explored the gender difference and E2 effect on glucose uptake and glycogen storage in skeletal muscle during early-phase sepsis. We measured the blood concentrations of epinephrine and cortisol, and found that the two counter- regulatory hormones were sharply increased by CLP but E2 did not reverse it. We next assessed insulin-stimulated glucose uptake in skeletal muscle during early sepsis, and the results showed that insulin sensitivity (EC50) of [3H]-2-deoxyglucose (2-DG) uptake was reduced in both extensor digitorum longus (EDL) muscle and soleus (SOL) muscle from male rats and was significantly worse than female rats. Glycogen content was diminished in skeletal muscle of male rats only at 3 hour post-CLP. E2 administration to male rats could improve these CLP-induced defects except epinephrine and cortisol. In view of these findings, we infer that early sepsis-induced insulin resistance in male rats is more serious than female rats, and result in aberrant glucose uptake in skeletal muscle, expediting muscle glycogen break down. Taken together, these changes caused higher blood glucose level in males than females, and similar pattern was also observed for mortality. E2 treatment also appeared to ameliorate the disturbance of glucose metabolism and to reduce the mortality of sepsis.