Comparative studies of (-)-epicatechin and insulin confirm the similarity between these two compounds. They both exert protective effects on human erythrocyte osmotic fragility, stimulate oxygen uptake in fat cells and tissue slices of various organs, increase the glycogen content in rat diaphragms while simultaneously increasing the glucose uptake, and inhibit theophylline induced lipolysis in isolated fat pads.

Despite their similar properties, both insulin and (-) epicatechin act by a different mechanism of action due to separate binding sites.

Correlations between (-)-epicatechin stimulated cAMP content in the islets of Langerhans and insulin release as well as the conversion of proinsulin to insulin and cathepsin activity have been observed. These effects were studied in mature and immature rats. It was found that exposure of the islets  in vitro to (-)-epicatechin increased the cAMP content of the islets even with non-stimulatory concentrations of glucose. The increase in cAMP activity is attributed to epicatechin and glucose that raise intracellular Ca concentration in the islets.

(-)-Epicatechin has also been shown to have an effect on the conversion of proinsulin to insulin. Several researchers have attributed the conversion to cathepsin B (an enzyme that digests proteins) although it is not known how this compound is involved. Ahmad and coworkers confirmed their findings. They observed a corresponding increase in the cathepsin B activity in islets with the conversion of proinsulin to insulin even at suboptimal glucose concentrations.

In addition, it was determined that aging affects the response to (-)-epicatechin. Immature rats responded better to epicatechin with respect to insulin release and cAMP content of islets compared to their mature counterparts. With maturation there is a sharp decline in the islets response to (-)-epicatechin although the size of the islets and number of b-cells increase with age.

Although basal insulin release at 2mM glucose did not significantly alter with age, (-)-epicatechin-stimulated insulin release at 2 mM glucose decreased significantly with age. Perhaps, aging may cause configurational changes in the beta-cell membrane and the arrangements of the membrane compartments that affect the binding of insulin secretagogues to the membrane.

Marsupsin and pterostilbene, like oral hypoglycemic agents (e.g. metformin), may have insulin-like effects on several tissues by suppressing hepatic gluconeogenesis, stimulating glycolysis, inhibiting glucose absorption from the intestine, or acting by other mechanisms.