Restoration of ß-Adrenergic Signaling and Activity of Akt-Kinase and AMP-Activated Protein Kinase with Metformin in the Myocardium of Diabetic Rats.

We studied the effect of metformin (100 and 200 mg/kg/day, 4 weeks) on the adenylyl cyclasestimulating effects of ß-agonists and relaxin in the myocardial membranes and on activities of Akt-kinase, an effector component of insulin signaling, and AMP-activated protein kinase (AMPK), a cellular energy sensor, in the myocardium of rats with type 2 diabetes mellitus induced by high-fat diet and streptozotocin. Metformin normalized the ratio of adenylyl cyclase effects of ß1/2- and ß3-agonists in the myocardial membranes, that is reduced in DM2, and restored phosphorylation of Akt-kinase by Ser473 and AMPK by Thr172 in the myocardium of diabetic rats. The effect of metformin in a dose of 200 mg/kg/day was more pronounced. Thus, the cardioprotective effect of metformin is due to its ability to restore the adrenergic and insulin regulation in cardiomyocytes and their energy status.

Effects of Bariatric Surgeries on the Size of Myocardial Infarction and Ghrelin Level in Rats with Experimental Decompensated Type 2 Diabetes Mellitus.

The effects of bariatric surgeries (sleeve gastrectomy and ileal transposition) on the dynamics of changes in ghrelin level were studied in rats with severe decompensated type 2 diabetes mellitus under conditions of glucose challenge as well as on the size of myocardial infarction in these animals. Diabetes was modelled by high fat diet and a single administration of streptozotocin (25 mg/kg, intraperitoneally). Both bariatric surgeries significantly decreased glucose-induced ghrelin level in the blood of rats with type 2 diabetes mellitus, which attested to an increase in the tissue sensitivity to ghrelin. Sleeve gastrectomy resulted in a decrease in the size of myocardial infarction in diabetic rats, which was calculated as the ratio of the necrosis zone to the zone of the risk of myocardial infarction. Ileal transposition had no effect on this parameter. Our data can be used as the basis for optimization of treatment approaches when using bariatric surgery in the treatment of patients with severe forms of type 2 diabetes mellitus with a high risk of cardiovascular diseases.

Multimodal Optical Diagnostics of Glycated Biological Tissues.

Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia accompanied by the disruption of carbohydrate, lipid, and proteins metabolism and development of long-term microvascular, macrovascular, and neuropathic changes. This review presents the results of spectroscopic studies on the glycation of tissues and cell proteins in organisms with naturally developing and model diabetes and in vitro glycated samples in a wide range of electromagnetic waves, from visible light to terahertz radiation. Experiments on the refractometric measurements of glycated and oxygenated hemoglobin in broad wavelength and temperature ranges using digital holographic microscopy and diffraction tomography are discussed, as well as possible application of these methods in the diabetes diagnostics. It is shown that the development and implementation of multimodal approaches based on a combination of phase diagnostics with other methods is another promising direction in the diabetes diagnostics. The possibilities of using optical clearing agents for monitoring the diffusion of substances in the glycated tissues and blood flow dynamics in the pancreas of animals with induced diabetes have also been analyzed.

[The effect of different types of bariatric surgery on the metabolic and hormonal parameters in rats with decompensed form of type 2 diabetes mellitus.]

Currently, one of the approaches to correct metabolic disorders in the type 2 diabetes mellitus (DM2) with obesity are bariatric surgery (BS), including sleeve gastrectomy (SG), gastric bypass (GB) and ileal transposition (IT). However, their effectiveness and impact on the hypothalamic signaling and hormonal status in severe forms of DM2 without obesity remain little studied. The aim of the work was to study the effect of IT, SG and GB on the insulin, leptin, ghrelin and glucagon-like peptide-1 (GLP-1) levels in the blood and on the expression of the genes encoding the main components of the hypothalamic signaling systems in rats with decompensated form of DM2, which was induced by a high-fat diet (3 months) and a single low dose of streptozotocin (25 mg/kg, 2 months after the start of the diet). In diabetic rats, a significantly expressed hyperglycemia, an impaired glucose tolerance, a decrease in glucose-stimulated GLP-1 level, a slight decrease in the insulin and leptin levels and an slight increase in ghrelin level were detected. In the hypothalamus, the expression of the genes encoding GLP-1 receptor, orexigenic agouti-related peptide (AgRP), as well as phosphotyrosine phosphatase 1B and SOCS3, the negative regulators of the leptin and insulin pathways was increased. In diabetic rats, the IT reduced the glucose levels 120 minutes after glucose load, increased the basal and glucose-stimulated GLP-1 levels, normalized the gene expression for phosphotyrosine phosphatase 1B, SOCS3, AgRP and GLP-1 receptor, which indicates the restoration of the hypothalamic signaling responsible for the control of energy metabolism and insulin sensitivity. In the case of SG and GB, an improvement in the glucose tolerance was found, and in the case of SG, an increase in the basal and glucose-stimulated GLP-1 levels was shown. However, no significant effect on the expression of the hypothalamic genes in SG and GB was found. Thus, IT is the most effective of all studied BS in the treatment of severe forms of DM2 without obesity.