Neohesperidin Dihydrochalcone Improves Hyperglycemia and Insulin Resistance in Diabetic Zebrafish

Neohesperidin dihydrochalcone (NHDC), a bicyclic flavonoidcompound,has many important physiological functions. However, the underlyinghypoglycemic mechanism of NHDC is not clear. We investigated the mechanismunderlying the antihyperglycemic effects of NHDC by cloning diabeticzebrafish. NHDC (0.5 mg/mL) substantially alleviated hyperglycemiaand hyperinsulinemia in diabetic zebrafish, reduced fasting bloodglucose, glycated serum protein, serum glucose, triacylglycerol, cholesterol,and insulin levels and HOMA-IR, TNF-& alpha;, IL-6, G6P, and PEPCKactivities, and increased GCK activity. Histological examination ofhepatic tissues showed that NHDC substantially reduced diabetes-exacerbatedlipid accumulation in liver tissues. Transcriptomic and polymerasechain reaction analyses indicated that NHDC improves insulin resistancepossibly by activating the insulin pathway (PI3K/AKT) and regulatingglucolipid metabolism and inflammatory responses. This study demonstratedthe anti-insulin resistance properties of NHDC and its effect on hyperglycemiaand hypolipidemia, providing new insights into the antidiabetic effectsof NHDC and its use as a dietary supplement for diabetic therapy.