Neohesperidin Dihydrochalcone Improves Hyperglycemia and Insulin Resistance in Diabetic Zebrafish

Neohesperidin dihydrochalcone (NHDC), a bicyclic flavonoid compound, has many important physiological functions. However, the underlying hypoglycemic mechanism of NHDC is not clear. We investigated the mechanism underlying the antihyperglycemic effects of NHDC by cloning diabetic zebrafish. NHDC (0.5 mg/mL) substantially alleviated hyperglycemia and hyperinsulinemia in diabetic zebrafish, reduced fasting blood glucose, glycated serum protein, serum glucose, triacylglycerol, cholesterol, and insulin levels and HOMA-IR, TNF-α, IL-6, G6P, and PEPCK activities, and increased GCK activity. Histological examination of hepatic tissues showed that NHDC substantially reduced diabetes-exacerbated lipid accumulation in liver tissues. Transcriptomic and polymerase chain reaction analyses indicated that NHDC improves insulin resistance possibly by activating the insulin pathway (PI3K/AKT) and regulating glucolipid metabolism and inflammatory responses. This study demonstrated the anti-insulin resistance properties of NHDC and its effect on hyperglycemia and hypolipidemia, providing new insights into the antidiabetic effects of NHDC and its use as a dietary supplement for diabetic therapy.