APMCG-1 improves cardiomyocytes in larvae
To validate whether APMCG-1 normalizes cardiomyocytes and skeletal myoblasts capacities, we analyzed the functional and energy metabolism in of type 2 diabetic zebrafish model. The heart rate of zebrafish refers to the heart beats per minute, and the change in heart rate is an important index for the evaluation of cardiac function. Compared with that of the untreated group, the heart rate of zebrafish in the model group decreased, and the mortality increased. Compared with the model group, different concentrations of APMCG-1 increased the heart rate and decreased mortality (Fig. 4A, 4B). After five days of continuous high-cholesterol feeding, accumulation of lipid deposition was observed at the bifurcation of blood vessels, which indicated that high blood lipid levels can promote and cause the occurrence of atherosclerosis and lead to the localization of atherosclerosis (Fig. 4C). The blood flow rate of larvae in the model group was significantly decreased, and the decreased blood flow rate was significantly recovered after 50 μg/mL APMCG-1 treatment (Fig. 4D). Therefore, 50 μg/mL APMCG-1 was selected for follow-up experiments.
Insulin resistance is an independent risk factor for diabetes. Compared with the model group, the increased concentrations of APMCG-1 decreased the levels of FBG, T-CHO, and TG dose-dependently in the treated group. This finding illustrates that APMCG-1 regulated blood glucose and lipid levels in type 2 diabetic zebrafish. CK-MB is a subtype of CK that is found only in the heart and cTnI is a specific marker of myocardial necrosis. Thus, CK-MB and cTnI are associated with myocardial injury. We observed that APMCG-1 markedly decreased the levels of CK-MB and cTnI compared with those in the model zebrafish, which revealed that APMCG-1 can reduce cardiac injury (Fig. 4E). Compared with the model group, APMCG-1 significantly increased the levels of SOD, GSH-PX and CAT, and decreased the level of MDA, TNF-ɑ and IL-6 in the treatment group (Fig. 4F). Collectively, the data suggested that APMCG-1 predominately promotes glucose uptake and metabolism in cardiomyocytes and skeletal myoblasts.