Restoration of hypothalamic signaling systems as a cause of improved metabolic parameters in rats with neonatal diabetes model during treatment with bromocriptine mesylate

Abstract

One approach to correction of diabetes mellitus 2 type (DM2) and its complications is the use of bromocriptine mesylate (BCM), a selective agonist of the dopamine receptor type 2 (DA2R). However, the effectiveness and mechanisms of the action of BCM in the treatment of severe forms of DM2 forms currently not understood. The purpose of this study was to investigate the influence of 4-week treatment of male rats with neonatal DM2 model using BCM (300 mg/kg daily) on their metabolic parameters and on the activity of the adenylyl cyclase signaling system (ACSS) in the hypothalamus. Exposure to BCM restored glucose tolerance and glucose utilization by exogenous insulin, normalized lipid metabolism, and lowered triglycerides and atherogenic cholesterol levels, which are elevated in DM2. In the hypothalamus of diabetic rats treated with BCM, the regulation of ACSS by agonists of melanocortin receptors type 4 (MC4R), DA2R, and serotonin 1B-subtype receptors and expression of the Mc4r gene encoding MC4R were restored. Furthermore, BCM treatment did not influence the insulin levels in the blood and its production by pancreatic β-cells. The data indicate that the use of BCM to correct severe forms of experimental DM2 holds promise and show that the therapeutic potential of this drug is based on its ability to restore signaling systems of the hypothalamus that are sensitive to monoamines and peptides of the melanocortin family, which are responsible for the control of energy metabolism and insulin sensitivity.