The Pathogenetic Rationale the Ways of Experimental Type 2 Diabetes Mellitus Modeling

Abstract

Relevance. When modeling experimental type 2 diabetes mellitus (T2DM), various schools and research groups receive significant variability in tissue changes, which is difficult to compare and extrapolate as a specific pathogenic or pharmacological effect. The lack of standard operating procedures agreed upon in the scientific community greatly complicates the interpretation of the result. Therefore, the creation of a uniquely pathogenetic animal model of CD2 in animals is an urgent task.
 Objective. Determination of the complex of exogenous effects for the most efficient reproduction of the experimental model of T2DM in rats and the pathogenetic justification of the changes in the body to study the central mechanisms of homeostasis regulation and their pharmacological correction.
 Materials and methods. T2DM was model in rats by feeding a high-fat diet (HFD) with additional streptozotocin induction. The model was evaluated by anthropometric measurements, studies of biochemical parameters, an insulin tolerance test, analysis of the spectrum of fatty acids in the composition of tissues. Statistical data processing was performed with using the IBM SPSS Statistics 23.
 Results. The obtained data were compared with our studies of the lipid metabolism of patients with varying degrees of diabetic retinopathy on the background of T2DM and analysis of the information content of biochemical markers to assess lipid metabolic disturbances on the background of hyperglycemia in patients. It was found that the simulation in rats of experimental T2DM by a food load of HFD (45%) + fructose 20% for 3 months followed by a single induction of streptozotocin (25 mg/kg) causes changes in lipid and carbohydrate metabolism in animals similar changes which are in the human with a diagnosed long-term diabetes and the development of microvascular complications.
 Conclusion. We determined the optimal combination of effects and developed a consistent experimental load scheme that allows us to obtain a symptom model of type 2 diabetes in an animal experiment. Using the diagnostic algorithm, which includes physiological and laboratory methods, the degree of damage to organs and systems was determined, a comparison was made with the level of metabolic disorders in patients with T2DM and people without diabetes. The given model is a pathogenetically grounded approach for further study of the central mechanisms of homeostasis regulation and their pharmacological correction

Effect of Propionic Acid on Diabetes-Induced Impairment of Unfolded Protein Response Signaling and Astrocyte/Microglia Crosstalk in Rat Ventromedial Nucleus of the Hypothalamus

“…The general scheme of animal experimental design is shown in Figure 1 . Experimental T2DM in rats was developed according to the standard protocol that was described previously [ 24 , 25 ]. Particularly, animals were fed a homogenous HFD mixture: thoroughly grounded standard rodent feed (34%) and premelted fat from lard (45%), medical bile acids (1%, for natural emulsification of fat in the intestine of rats and improvement of its absorption by enterocytes), and dry fructose (20%).…”

“…T2DM was developed after 3 months of high-fat diet (HFD) with the following single injection of STZ (25 mg/kg of b.w.) according to the protocol [ 25 ].…”

“…T2DM was developed after 3 months of high-fat diet (HFD) with the following single injection of STZ (25 mg/kg of b.w.) according to the protocol [25]. 4 Neural Plasticity (0.03 g) were lysed for 20 min in RIPA (1 : 9) in the presence of protease inhibitor cocktails (Sigma, USA) and then centrifuged for 20 min (14000 × g) at +4 2.8.…”

Regulation of the apoptosis/autophagy switch by propionic acid in ventromedial hypothalamus of rats with type 2 diabetes mellitus

“…The general experimental design is shown in Figure 1 a. To induce T2DM, rats were fed a homogenous HFD mixture: standard rodent feed (34%), pre-melted fat from lard (45%), medical bile acids (1%, for natural emulsification of fat in the intestine of rats and improvement of its enteral absorption), and dry fructose (20%) [ 35 ]. Additionally, STZ administration was performed at a dose 25 mg/kg of b.w.…”

The Metabolic Effect of Cellular Protein Kinases Blockade on the Experimental Diabetes

“…Тваринам 3-ї групи (n = 35) моделювали ЦД2 застосуванням висококалорійної жирової дієти, збагаченої легкозасвоюваними вуглеводами (фруктоза) [17,18]. Суміш для годування виготовляли змішуванням подрібненого комбікорму (55,6%), перетопленого свинячого сала (33,3%) і фруктози (11,1%; "ADM® Crystalline Fructose C", Болгарія).…”