Background: Insulin increases glucose uptake in muscles and fat and inhibits hepatic glucose production,
thus serving as the primary regulator of the blood glucose level. In type 2 diabetes, insufficient insulin release
and suppressed insulin action [named insulin resistance] lead to increased glucose production in liver and
decreased glucose uptake by muscles and fat tissues, resulting in elevated blood glucose concentration which is
dangerous to human health. Therefore, the anti-diabetic therapies are aimed at inhibiting excess blood glucose.
Methods: A comparative analysis of two distinct glucose-lowering modes was used to develop a new feedback
model for the purpose of identification of pharmacological targets in diabetes treatment.
Results: The current brief opinion proposes an original feedback control of glucose-lowering regulation and its
models which allow comparing two distinct strategies of glucose level correction, i.e., one of them allows reducing
the increased threshold of insulin resistance, whereas the other allows overcoming this threshold/barrier using
exogenous insulin treatment. Also, this analytic research presents selected examples comparing the influence of
the two analyzed strategies on the normalization of glucose metabolism, their therapeutic potential and side effects
associated with additional weight gain. These models show the pathological mechanism by which exogenous
insulin provokes formation of a «vicious cycle» by its side effects associated with additional weight gain.
Conclusion: The presented model and findings can contribute to the development of new anti-diabetic targets and
drugs with minimal side effects.