Совместное применение метформина и интраназального инсулина нормализует чувствительность к глюкозе и гормональный статус у крыс с диабетом 2 типа

Abstract

Metformin is the first-line drug of choice in the treatment of type 2 diabetes mellitus (T2DM). It acts on peripheral tissues as well as different regions of the brain and restores metabolic and hormonal parameters. Insulin administered intranasally (II) enters the brain and normalises the insulin signaling in the central nervous system, including the hypothalamus, which is weakened in T2DM. This improves the central regulation of metabolism, food intake and functions of the endocrine system. We suggested that the combined use of metformin and II should enhance their restorative effect on the metabolic and hormonal parameters in T2DM. The study was conducted on male rats with T2DM2 induced by a high-calorie diet and a low-dose streptozotocin. The male rats with T2DM were administered metformin (4 weeks, 100 mg/kg/day) and II (4 weeks, 0.5 IU/rat/day), separately and together. The aim of the study was to analyse the effect of the treatment on glucose sensitivity and the levels of insulin, leptin, glucagon-like peptide-1 (GLP-1), thyroid hormones and testosterone. Metformin monotherapy improved glucose homeostasis and normalised basal and glucose-stimulated levels of insulin, leptin and GLP-1. Co-administration of metformin with II enhanced the restorative effects of metformin on tissue insulin sensitivity and leptin levels. Metformin and II normalised the levels of thyroid hormones and testosterone, and their combined use caused the activation of the thyroid system, as indicated by an increase in the levels of thyroid hormones. The data obtained indicate the prospects for the combined use of metformin and II for improving metabolic and hormonal parameters. It may also be used to improve the thyroid and androgenic status in patients with T2DM.