Chitosan Oligosaccharide Alleviates Abnormal Glucose Metabolism without Inhibition of Hepatic Lipid Accumulation in a High-Fat Diet/Streptozotocin-Induced Diabetic Rat Model

This study investigated the effects of chitosan oligosaccharide (COS) on glucose metabolism and hepatic steatosis in a high-fat (HF) diet/streptozotocin-induced diabetic rat model. Male Wistar rats were divided into: (1) normal control (NC group), (2) HF diet (HF group), (3) streptozotocin (STZ)-induced diabetes with HF diet (DF group), and DF group supplemented with (4) 0.5% COS (D0.5F group), (5) 1% COS (D1F group), and (6) 5% COS (D5F group) for 4 weeks. COS supplementation significantly decreased the plasma glucose, BUN, creatinine, uric acid, triglyceride (TG), and total cholesterol (TC) levels, and hepatic glucose-6-phosphatase activity, and significantly increased hepatic hexokinase activity and glycogen content in diabetic rats; but the increased hepatic TG and TC levels could not be significantly decreased by COS supplementation. Supplementation of COS increased superoxide dismutase activity and decreased lipid peroxidation products in the diabetic rat livers. COS supplementation significantly increased phosphorylated AMP-activated protein kinase (AMPK) protein expression, and attenuated protein expression of hepatic phosphoenolpyruvate carboxykinase (PEPCK) and phosphorylated p38 and renal sodium-glucose cotransporter-2 (SGLT2) in diabetic rats. These results suggest that COS may possess a potential for alleviating abnormal glucose metabolism in diabetic rats through the inhibition of hepatic gluconeogenesis and lipid peroxidation and renal SGLT2 expression.