Chitosan reduces gluconeogenesis and increases glucose uptake in skeletal muscle in streptozotocin-induced diabetic rats.
Chitosan is a natural and versatile biomaterial with a blood-glucose-lowering effect in diabetic animals, but the mechanism of action is still unknown. This study was designed to investigate the possible mechanisms involved in the hypoglycemic activity of chitosan in rats with streptozotocin (STZ)-induced diabetes. Male Sprague-Dawley (SD) rats were divided into non-diabetic with cellulose (control), diabetic with cellulose (DM), and diabetic with low- (DM + LCS) and high- (DM + HCS) molecular-weight chitosan groups. After a 4 week feeding study, plasma glucose and fructosamine levels were increased while plasma leptin was decreased in the DM group when compared to the control group. These alternations caused by diabetes could be effectively reversed by both chitosan treatments. The increased gluconeogenesis-related signals including phosphoenolpyruvate carboxykinase (PEPCK) expression and phosphorylations of p38 and AMP-activated kinase (AMPK) in the livers of diabetic rats were attenuated by chitosans. Moreover, chitosan significantly increased muscle glucose uptake-related signals including Akt phosphorylation and glucose transporter-4 (GLUT4) translocation from the cytosol to membrane in the soleus muscles of diabetic rats. These results indicate that chitosan may possess a potential for alleviating type-1 diabetic hyperglycemia through the decrease in liver gluconeogenesis and increase in skeletal muscle glucose uptake and use.
Liu
Shing-Hwa
SH
Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China.
Chang
Yu-Han
YH
Chiang
Meng-Tsan
MT
D000818:Animals; D048271:Chitosan / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000378:metabolism*; D005943:Gluconeogenesis / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
D051275:Glucose Transporter Type 4; C495694:Slc2a4 protein, rat; D013311:Streptozocin; D048271:Chitosan; D051057:Proto-Oncogene Proteins c-akt; D019764:Phosphoenolpyruvate Carboxykinase (ATP); D005947:Glucose