Isosativan from Nigerian Propolis Modulates AMP-activated Protein Kinase, Glucose-6-Phosphatase and Lipoprotein Lipase levels in Rats with Insulin Resistance

Objective: This study investigated the effects of isosativan, a bioactive compound isolated from Nigerian propolis, on the activities of key metabolic regulators, including AMP-activated protein kinase (AMPK), glucose-6-phosphatase (G6Pase), and lipoprotein lipase (LPL), in an animal model of insulin resistance.Material and Methods: Male Wistar rats were fed a high-fat diet and fructose solution for 8 weeks to establish an animal model of insulin resistance. Eighteen of the animals were sorted into 3 groups: the insulin-resistant group, the isosativan group, and the metformin group, while a fourth group of 6 healthy rats served as the control group. The isosativan treatment group received daily oral administration of isosativan for 4 weeks, while the metformin group served as a positive control. Plasma glucose, insulin, and lipid profiles were measured, and the activities of AMPK, glucose-6-phosphatase in the liver, and lipoprotein lipase in the adipose tissue were assessed.Results: Compared to the control group, the insulin-resistant group showed significantly increased fasting plasma glucose and homeostatic model assessment of insulin resistance (HOMA-IR) levels. The high-fat diet and fructose consumption also disturbed the lipid profile. Treatment with isosativan improved insulin resistance and modulated the altered activities of AMPK, glucose-6-phosphatase, and lipoprotein lipase in insulin-resistant rats, indicating its potential and probable mechanism of improving glucose and lipid homeostasis.Conclusion: Isosativan, a compound isolated from Nigerian propolis, demonstrated the ability to modulate key metabolic regulators involved in insulin resistance, suggesting its therapeutic potential for managing metabolic disorders.