In the light of the emerging new data, the view of the hypothalamic-pituitary-adrenal-target organs system undergoes significant changes, and along with the negative feedback mechanism, there are suggestions of the existence of other regulatory mechanisms for synthesis, activation, and deactivation of glucocorticosteroids (GCS). However, there is currently a relatively small amount of data on the relationship between systemic and local cortisol production in tissues. The inconsistent increase in the number of patients with diabetes mellitus (predominantly type 2) and obesity poses new challenges in developing effective medicines and their delivery forms, Methods of timely detection and prevention of the development of the disease. Understanding these processes will create the necessary scientific basis for the search and development of new targets for the pharmacotherapy of diseases associated with a violation of synthesis, activation and action of GCS.