Experimental Models Of Diabetes Mellitus Research Articles

Effects of Some Olive Fruits-Derived Products on Oxidative Stress and Cardiovascular Biomarkers on Experimental Diabetes Mellitus.

The aim of this study is to assess the possible effect of olive seed oil (OSO) and destoned and dehydrated olive oil (DDOO), in comparison with extra-virgin olive oil (EVOO), on some cardiovascular biomarkers in an experimental model of diabetes mellitus. Diabetic animals showed evident alterations in biomarkers involved in the evolution of diabetic vasculopathy, marked by increases in biomarkers that favor vascular damage, which was between 1.5 and five times as many as those in non-diabetic animals, and a smaller number of biomarkers that protect against such damage (25-75% less than in healthy controls) was observed. The three oils administered decreased the concentration of biomarkers of vascular damage (35-45% in the serum lipid profile, 15-40% in early biomarkers of vascular inflammation and 20-60% in platelet aggregation and in thromboxane/prostacyclin imbalance). The greatest effect was by the antioxidant, both in the inhibition of lipid peroxidation and in the increase of glutathione. DDOO showed a significantly greater effect on oxidative stress and on thromboxane/prostacyclin imbalance than those shown by OSO and EVOO. This greater effect may possibly be explained by its higher triterpenoid content (913 mg/kg, compared to 113 mg/kg in OSO and 75 mg/kg in EVOO). We conclude, in the light of the results of this study, that these oils meet two basic conditions: they could improve the yield of the olive industry, and they equal, and may even increase, the beneficial effects of EVOO on cardiovascular disease.

Effect of a Triterpenoid-Rich Olive Oil on Chronic Kidney Disease in an Experimental Model of Diabetes Mellitus.

The aim of this study was to assess the effect of triterpenoids on the development of diabetic nephropathy in an experimental model of diabetes mellitus. For this purpose, a destoned and dehydrated olive oil (DDOO) was used, comparing its effects to a destoned olive oil (DOO). DDOO had a higher triterpenoid content than DOO but an equal content of alcoholic polyphenols. Four study groups (n = 10 animals/group) were formed: healthy rats, diabetic control rats (DRs), and DRs treated orally with 0.5 mL/kg/day of DOO or DDOO for two months. DRs showed impaired renal function (proteinuria, increased serum creatinine, decreased renal creatinine clearance) and morphology (glomerular volume and glomerulosclerosis). These alterations correlated with increased systemic and renal tissue oxidative stress and decreased prostacyclin production. DDOO administration significantly reduced all variables of renal damage, as well as systemic and renal oxidative stress, to a greater extent than the effect produced by DOO. In conclusion, triterpenoid-rich olive oil may prevent kidney damage in experimental diabetes mellitus.

PECULIARITIES OF RESPIRATORY CELLULAR IMPLICATIONS IN STREPTOZOTOCIN-INDUCED DIABETES: A FOCUS ON TYPE I ALVEOLOCYTES

Introduction. The escalating global prevalence of diabetes mellitus has ignited concerns, given its multifaceted repercussions that extend beyond conventional metabolic considerations. Recent scientific inquiries have firmly established a profound association between diabetes mellitus and abnormalities within the respiratory system, unveiling a nuanced interplay that transcends mere glycemic control. This study delves into the intricate and far-reaching influence of diabetes on the respiratory system, recognizing it as a vulnerable target organ susceptible to systemic repercussions. Compelling epidemiological evidence underscores a heightened prevalence of respiratory complications among individuals grappling with diabetes. This observation prompts a meticulous exploration of the pathophysiological underpinnings of this intricate relationship, spanning from molecular intricacies to clinical manifestations.
 The aim was to deepen our understanding of the impact of diabetes mellitus on the respiratory system by investigating the pathological alterations in type I alveolocytes within an experimental model of diabetes mellitus.
 Methods. In this experimental model we used 88 male Wistar rats (170-210 g). The rats were divided into three groups: Group 1 (n=10) consisted of intact rats; Group 2 (n=40) served as the control group, and Group 3 (n=38) constituted the experimental group where diabetes was induced by intraperitoneal administration of streptozotocin (Sigma, USA) diluted in 0.1 M citrate buffer with pH 4.5 at a dosage of 60 mg/kg of body weight. The control group received an equivalent volume of 0.1 M citrate buffer solution with a pH of 4.5 via intraperitoneal injection. All procedures were performed under sodium thiopental anesthesia at a dose of 60 mg/kg of body weight. Tissue samples were collected at intervals of 14, 28, 42, and 70 days post streptozotocin injection.
 For electron microscopy analysis, fragments of lung tissue were immersed in a 2.5% glutaraldehyde solution for fixation, followed by fixation in a 1% osmium tetroxide solution. After dehydration, the specimens were embedded in Epon Araldite. Sections, obtained through a "Tesla VS-490" ultramicrotome, underwent examination using a "PEM-125K" electron microscope.
 Results. Throughout the experiment, discernible changes in type I alveolocytes were observed. At 14 days, nuclei exhibited rounding or oval shape with uniform chromatin distribution. Mitochondria displayed small size, and the Golgi apparatus (GA) and granulated endoplasmic reticulum (GER) showed no significant alterations. By 28 days, nuclei adopted an oval shape, chromatin localized peripherally, and mitochondria exhibited diverse morphologies. Increased micropinocytotic vesicles indicated heightened cellular activity. At 42 days, hyperhydration became pronounced, nuclei displayed lower electron density, and cellular components showed advanced changes. By 70 days, dystrophic-destructive changes included low electron density nuclei, disorganized mitochondria, and fragmented GA and GER.
 Conclusion. This comprehensive ultrastructural analysis unveils the progressive impact of diabetes on type I alveolocytes, elucidating unique facets of pulmonary alterations over time. This study contributes to a growing body of knowledge, shedding light on the dynamic nature of pulmonary changes in diabetes mellitus, ultimately urging further exploration for a holistic understanding of its implications on respiratory health.

Photobiomodulation in diabetic rats: effects on morphological, pancreatic parameters and glucose homeostasis.

Photobiomodulation (PBM) has therapeutic effects on wound healing, diabetic microangiopathy and retinopathy. However, little is known about the use of PBM for the treatment of diabetes mellitus (DM). In this context, we aimed to evaluate the effects of PBM on pancreas morphology and insulin and glucose tolerance in an experimental model of DM. Thus, DM was induced by STZ (60 mg/Kg). Subsequently, the rats were treated with PBM (808 nm and 30 J/cm2). After euthanasia, morphometric parameters and immunoreactivity for insulin and 8-OHdG were evaluated in the pancreas. The results showed that treated animals had higher values of body mass and higher values in the number of beta cells in the pancreas. In conclusion, PBM resulted in decreased weight loss in STZ-induced diabetic rats and presented a stimulatory effect on the pancreas of the treated animals, highlighting the promising effects of this therapy in the clinical condition of DM.

Chrysin loaded nanovesicles ameliorated diabetic peripheral neuropathy. Role of NGF/AKT/GSK-3β pathway

Diabetic peripheral neuropathy (DPN) is a common diabetic complication. Chrysin (CHY) has many biological properties but poor oral bioavailability. This study investigates the effect of CHY and CHY-loaded nanovesicles (CHY-NVs) on streptozotocin (STZ)-induced DPN in rats. CHY-NVs were prepared by using film hydration method. The formula with the best entrapment efficiency%, lowest particle size, highest zeta potential, and highest in vitro CHY released profile was selected, characterized by Differential scanning calorimetry, Fourier transformation infrared spectroscopy analysis, and examined by Transmission electron microscope. Acute toxicity test, pharmacokinetic study and experimental model of diabetes mellitus were performed on the selected formulation. Wistar rats were considered diabetic by administration of a single intraperitoneal dose of STZ (50 mg/kg). 48 h after STZ administration, hyperglycemic rats were randomly assigned into four groups, one group of untreated hyperglycemic rats and the other three groups received daily oral doses of unloaded NVs, CHY-NVs (25 mg/kg), and CHY-NVs (50 mg/kg), respectively for 21 days. Moreover, five additional groups of healthy rats received: distilled water (control), free CHY, unloaded NVs, and CHY-NVs respectively for 21 days. CHY and CHY-NVs maintained body weight and reduced STZ-induced behavioral changes in rotarod, hind paw cold allodynia, tail cold allodynia, tail flick, and hot plate tests. CHY and CHY-NVs lowered blood glucose, glycated hemoglobin, elevated serum reduced glutathione (GSH), and reduced plasma malondialdehyde (MDA) levels. CHY-NVs elevated phosphatidylinositol 3-kinase (Pi3k), phosphorylated protein kinase B (p-AKT), and reduced nuclear factor kappa B (NF-κB), interleukin-6 (IL-6) in sciatic nerve homogenate. CHY and CHY-NVs increased nerve growth factor (NGF) and decreased glycogen synthase kinase-3β (GSK-3β) gene expressions in the sciatic nerve. In conclusion, CHY and CHY-NVs ameliorated STZ-induced DPN behavioral and histopathological changes via attenuating hyperglycemia, exerting anti-oxidant, anti-inflammatory effects, activating NGF/p-AKT/GSK-3β pathway, and its anti-apoptotic effect. The best pharmacokinetic profile and therapeutic effect was observed in rats treated with CHY-loaded NVs.

Drug Promising Effect for Diabetic Mice of CARICA PAPAYA Leaves

Diabetics Mellitus is a major problem for city people worldwide. The objective of this study is finding the anti-diabetic and anti-hyper lipidaemic activity by using Carica papaya leaves. This leaves are not generally eaten but this leaves were eaten during dengue fever. The leaves extract is used for the treatment of diabetes and cancer. This leaves were collected from different place of Bangladesh and made methanolic extract then this extract was feed four groups of mice. The results showed that there was a significant (p<0.001 to p<0.05) reduction in blood glucose concentration (mmol/L) by the methanolic extract of C. papaya leaves at dose 100 mg/kg, 200 mg/kg and glibenclamide (used as standard) 5mg/kg body weight. C. papaya leaves extract also regulated the serum lipid profile levels significantly (p<0.001) at same dose in experimental model of diabetes mellitus. The level of serum SGPT, SGOT and CRP were also seen change to the normal level notably (p<0.001) by the oral administration of methanolic extract of C. papaya leaves. In conclusion this research finding indicate that the methanolic extract of Carica papaya leaves contains bioactive substances with hypoglycemic potency.

Beta-Receptor Blockade Reproduces Electrophysiological Effects of Early Diabetes Mellitus in Ventricular Myocardium

Diabetes mellitus (DM) increases the risk of sudden cardiac death, which suggests the involvement of arrhythmogenic mechanisms. Among other changes, DM causes cardiac autonomic neuropathy (CAN), but its role in electrophysiological myocardial remodeling is unclear. The objective of the present study was to test the effects of β-adrenergic blockade regarding ventricular spatiotemporal electrophysiological properties in an experimental DM model. Epicardial mapping (64-lead sock electrode array) was done in 13 control and 11 alloxan-induced DM rabbits. Activation times (AT), end of repolarization times (RT), and activation-repolarization intervals (ARI) were determined as dV/dt min during QRS, dV/dt max during T-wave, and RT-AT difference, respectively. The β-adrenergic blockade was produced by esmolol infusion (0.5 mg/kg, i.v.). It was found that the early-stage DM in rabbits was characterized by relatively mild changes in ventricular myocardium, which did not involve ventricular activation and the average duration of repolarization. The signature of this stage was the local prolongation of repolarization, which pertained to the RV apical region. The blockade of β-adrenergic receptors in healthy animals produced a ventricular spatiotemporal repolarization pattern similar to that observed in diabetic rabbits with the local apical prolongation of repolarization. On the other hand, the blockade of β-adrenergic receptors in diabetics prolonged the relatively short basal repolarization. It can be concluded that β-adrenergic blockade in healthy animals reproduced the early-stage DM effects on the spatiotemporal electrophysiological properties of the ventricular myocardium. This demonstrated the role which CAN could play in the electrical remodeling of ventricular myocardium in early-stage DM.

Effect of Tributyrin Supplementation on Glucose Levels, Liver and Kidney Integrity in an Experimental Model of Diabetes Mellitus

Effect of Tributyrin Supplementation on Glucose Levels, Liver and Kidney Integrity in an Experimental Model of Diabetes Mellitus

Monoamine oxidase contributes to the metabolic memory in diabetic mice

Monoamine oxidase (MAO) with 2 isoforms, A and B, are mitochondrial enzymes that recently emerged as important cardiovascular sources of reactive oxygen species. The aim of the present study was to assess the contribution of monoamine oxidase (MAO) to the “metabolic memory” phenomenon, as mechanism underlying the persistent oxidative damage and endothelial dysfunction in an experimental model of diabetes mellitus in mice. We hypothesized that: (i) MAO is an important contributor to vascular oxidative stress, in context of diabetes, even after glucose normalisation and (ii) selective MAO-A and MAO-B inhibition (clorgyline and selegiline, 1 mg/kg/day, 1 week) will reduce oxidative stress and improve vascular reactivity. Our results showed that: (i) MAOs expression increased in mice aortas (assessed by qRT-PCR and immune fluorescence) after 2 weeks of hyperglycemia together with high ROS generation (assessed by spectophotometry and confocal microscopy – DHE staining) and impaired vascular relaxation, (ii) glucose normalization (glargine, 10 U/kg/day, 1 week) did not significantly reduced ROS generation, and (iii) in vivo administration of MAO inhibitors (in addition to insulin) reduced ROS levels and improved vascular relaxation in diabetic mice. In conclusion, MAOs represent a potential therapeutic target for vascular diabetic complications. MAO inhibitors are viable candidates for drug repurposing as vasculo-protective agents in diabetes. Research supported by the university internal grant code 6POSTDOC/1871/12.02.2020.

Anti-inflammatory, hypoglycemic and hypolipidemic effects of Stevia rebaudiana bertoni leaf extract in an experimental model of diabetes mellitus and obesity in laboratory animals

Introduction. The paper presents the results of experimental studies focused on assessing the anti-inflammatory, hypoglycemic and hypolipidemic effects of Stevia rebaudiana Bertoni leaf extract. The study was conducted on an experimental model of "zinc" diabetes in white male Wistar rats and under conditions of acute hyperlipidemia caused by the Tween-80 detergent. The aim of the study was to evaluate the feasibility of using Stevia rebaudiana Bertoni leaf extracts in the diet as a natural sweetener for the organizing nutrition of overweight and diabetic people, including educational settings for children, on the model of induced diabetes mellitus and acute hyperlipidemia in laboratory animals. Materials and Methods. In order to solve the research problem, the authors utilized the following techniques: assessing the biochemical parameters of blood serum, determining the level of glucose in the blood, lipid formula and delayed-type hypersensitivity reaction. Theoretical methods involved reviewing and analyzing Russian and international academic articles. Results. The findings of this study suggest that it is possible to use Stevia rebaudiana Bertoni leaf extracts as a natural sugar substitute in the diet of people with overweight and diabetes mellitus, as well as for prophylaxis in healthy people, including meals for children in educational settings. Conclusions. The article concludes that an immunomodulatory effect and the absence of side effects of the Stevia rebaudiana Bertoni leaf extract confirm its usage in the daily diet of the population.

Distilled liquid smoke coconut shell attenuates the cytokine profile of macrophages in oral ulcer in experimental model of diabetes mellitus

Pharmacological and Pharmaceutical Profile of Valsartan: A ReviewNadeem Siddiqui, Asif Husain, Lakshita Chaudhry, M Shamsher Alam, Moloy Mitra, Parminder S. Bhasin

GC–MS and HPLC analysis of antiglycogenolytic and glycogenic compounds in kaempferol 3–O–gentiobioside containing Senna alata L leaves in experimental rats

BackgroundMedicinal herbs have received attention as an alternative to prescription medications. Diabetes mellitus is a chronic disease that affects the normal metabolic pathways in several organs. The purpose of this study was to determine the metabolites responsible for the antiglycogenolytic and glycogenic effects of a hydroethanolic extract of Senna alata L in an experimental model of diabetes mellitus; the male albino Wister rat treated with streptozotocin. ResultsThe therapeutic effects of Glibenclamide (0.6 mg/kg body weight) and S. alata L (400 mg/kg body weight) extracts were compared. The oral administration of this extract to diabetic rats resulted in a significant decrease in the levels of glycogenolytic factors that included: glycogen phosphorylase, glucose 6 phosphatase, glycosylated haemoglobin, and lactate dehydrogenase, and a significant increase in the levels of glycogenic factors such as plasma insulin, glycogen synthase, liver glycogen, hexokinase, pyruvate kinase After administration of the plant extract, the observed changes in the activities of these factors were found to be statistically significant and returned to near-normal levels. Additionally, the S. alata extract increased muscle and liver glycogen levels, demonstrating S. alata L's anti-diabetic properties. HPLC analysis identified Kaempferol 3–O–gentiobioside, while GCMS analysis showed the presence of phytol, stigmasterol, sitosterol, dimethyl derivatives, methyl esters, and octanoic acid derivatives. ConclusionThis work provides experimental evidence for the anti-diabetic potential of S. alata extract, which may result from the existence of beneficial bioactive chemicals. The aberrant metabolic enzymes in streptozotocin-induced diabetic rats' livers were restored following regular treatment with S. alata extract. As a result, S. alata leaves can affect blood glucose levels.

ИНСУЛИН + -КЛЕТКИ И ОСНОВНЫЕ ТРАНСКРИПЦИОННЫЕ ФАКТОРЫ (PDX1, MAFA И NGN3) В ПЕЧЕНИ ЖИВОТНЫХ ПРИ ЭКСПЕРИМЕНТАЛЬНОМ МОДЕЛИРОВАНИИ САХАРНОГО ДИАБЕТА 1-ГО И 2-ГО ТИПА

Due to a high occurrence of diabetes mellitus (DM) and its complications, insulin-positive cells detected in different organs are of great interest as they can probably partially compensate for insulin deficiency in diabetes mellitus. The development of pancreatic β-cells is regulated by the consecutive expression of transcription factors, among which Pdx1, MafA and Ngn3 are most extensively explored. Specifically, these factors have been reported to be able to transdifferentiate a broad variety of cell types into insulin-positive cells. The goal of this study was to characterize insulin-positive (insulin+) cells in the liver and to evaluate the expression of transcription factors Pdx1, MafA and Ngn3 involved in their differentiation in an alloxan-induced rat model of type 1 diabetes mellitus (T1D) and streptozotocin-nicotinamide-induced rat model of type 2 diabetes mellitus (T2D). Experiments were carried out on male Wistar rats. In experimental animals, plasma levels of glucose, glycosylated hemoglobin and insulin were determined. The oral glucose tolerance test was performed and the insulin resistance index (HOMA-IR) was calculated. The expression of Pdx1+, MafA+ and Ngn3+ was investigated immunohistochemically. Insulin+, Pdx1+, MafA+ and Ngn3+ cells were detected in the liver both of healthy animals and those with experimental models of T1D and T2D. The largest number of insulin+ cells was found in animals with streptozotocin-nicotinamide-induced T2D, wherein cells were localized throughout the hepatic lobule. In an alloxaninduced model of T1D, these cells were detected mainly at the periphery of the hepatic lobule. The number of Pdx1+, Mafa+ and Ngn3+ hepatic cells was different in intact animals vs. those with experimental DM. A correlation was established between the number of Ngn3+ cells and insulin+ cells in alloxan-induced DM, as well as between the number of MafA+ cells and insulin+ cells in both types of experimental DM. Thus, in rats with both experimental models of DM, the number of insulin+, Pdx1+ and MafA+ cells in the liver increases compared to intact animals. Localization and the number of insulin+ cells varies depending on the experimental model of DM. At the same time, the number of Pdx1+ and MafA+ cells increases in an alloxan-induced model of T1D compared to a streptozotocin-nicotinamide-induced model of T2D. There is a correlation between the number of insulin+ and MafA+ cells both in T1D and T2D models and between the number of insulin+ and Ngn3+ cells in a T1D model only.

Hypoglycemic activity on Putranjiva roxburghii bark. in alloxan induced diabetic rats

Diabetes mellitus is the most common endocrine disorder that impairs glucose homeostasis resulting in severe diabetic angiopathy retinopathy, neuropathy nephropathy, and causing neurological disorders due to anxiety in utilization of glucose. I present diabetes study was induced in albino rat models with the alloxan monohydrate. Putranjiva roxburghii bark. has been claimed to possess antidiabetic properties by some investigators. The present study was undertaken to screen the hypoglycemic activity of ethanol extracts of leaves of Putranjiva roxburghii. The results showed that it has significant anti-hyperglycemic effect in experimental model of diabetes mellitus.

Morphological Characteristics of Intestinal Vessels of Animals with an Experimental Model of Diabetes Mellitus Type 2 Complicated by Microangiopathy

Diabetes mellitus and its complications are considered far from unresolved problems of modern medicine.An important aspect in solving fundamental problems is experimental research aimed at assessing the stateof change of pathogenetic important key positions in the development of such a formidable complicationof diabetes as angiopathy. On the other hand, surgeons’ great interest in bariatric and metabolic surgery,as method of surgical treatment of type 2 diabetes mellitus, requires in-depth studies to assess the stateof angiogenic changes in the organs of the gastrointestinal tract, namely in the intestine. The articledescribes the morphological changes in the vascular capillary bed in the dynamics of the development ofa new experimental model of diabetes mellitus, namely the chemical method of diabetic angiopathy. Thedevelopment of an experimental model of diabetic angiopathy showed the staged nature of the changes inthe form of the initial signs of angiopathy, with perivascular infiltration and edema in the form of congestiveplethora in the flesh until the development of vascular hyalinosis, which indicates the irreversibility of theprocesses of pathological transformation. Thus, the results of morphological studies in the dynamics ofmodeling of diabetic angiopathy indicate the development of diabetes mellitus with its complication in theform of microangiopathy.

591-P: Macrophage IL-1beta–Dependent VEGF-A Expression Is Required for Inflammatory Arteriogenesis and Wound Healing in Type 2 Diabetes

Impaired wound healing in patients with diabetes mellitus (DM) is a major source of morbidity and mortality. Current treatments for diabetic wounds are modestly effective at promoting healing. Recently, we identified an important role for inflammatory macrophage VEGF-A production in consequent angiogenesis/arteriogenesis required for adequate wound healing. We sought to understand the impact of diabetes on inflammatory angiogenesis and consequent healing. We hypothesized that diabetes mellitus (DM) results in reduced inflammatory macrophage VEGF-A expression with consequent impairments in angiogenesis-dependent wound healing. Mice with experimental diabetes demonstrated profound delays both in wound healing using a dermal punch biopsy model and in perfusion recovery using the femoral artery ligation model of hind limb ischemia. VEGF-A expression is highly upregulated in “classic inflammatory” macrophages relative to “alternatively activated” or wound healing macrophages. This is supported by a strong association between IL-1β and VEGF-A expression. In order to understand whether this relationship between IL-1β and VEGF-A was causal, we generated a novel mouse with a LoxP flanked IL-1β allele to create an inducible macrophage deletion of IL-1β. Myeloid IL-β deletion resulted in severely impaired macrophage VEGF-A expression and consequent decreases in angiogenesis and wound healing, consistent with the experimental model of DM. Moreover, macrophages from diabetic mice demonstrated reduced expression of IL-1R signaling complex components along with consequent reductions in VEGF-A expression. Defining inflammatory macrophages as key, early drivers of angiogenesis supports a paradigm shift away from inflammation-suppression for adequate wound healing, allowing for macrophage reprograming strategies that promote appropriate inflammation-dependent healing responses. Disclosure C.S. Mantsounga: None. Funding National Institutes Health (1R01HL139795)

Molecular mechanisms of action and physiological effects of the proinsulin C-peptide (a systematic review)

The C-peptide is a fragment of proinsulin, the cleavage of which forms active insulin. In recent years, new information has appeared on the physiological effects of the C-peptide, indicating its positive effect on many organs and tissues, including the kidneys, nervous system, heart, vascular endothelium and blood microcirculation. Studies on experimental models of diabetes mellitus in animals, as well as clinical trials in patients with diabetes, have shown that the C-peptide has an important regulatory effect on the early stages of functional and structural disorders caused by this disease. The C-peptide exhibits its effects through binding to a specific receptor on the cell membrane and activation of downstream signaling pathways. Intracellular signaling involves G-proteins and Ca2+-dependent pathways, resulting in activation and increased expression of endothelial nitric oxide synthase, Na+/K+-ATPase and important transcription factors involved in apoptosis, anti-inflammatory and other intracellular defense mechanisms. This review gives an idea of the C-peptide as a bioactive endogenous peptide that has its own biological activity and therapeutic potential.

Perspectives of application of intranasally administered insulin for correction of metabolic and hormonal disorders in diabetes mellitus and metabolic syndrome

In recent years, the possibility of using intranasally administered insulin to treat Alzheimers disease and other cognitive disorders has been widely studied. At the same time, the possibility of its use in the treatment of diabetes mellitus is practically not investigated, which is due to the insufficient study of the molecular mechanisms of its action on the hormonal and metabolic status of the organism. The review discusses literature data and the results of our own research on the role of insulin in the central regulation of energy homeostasis, as well as on the experience of using intranasally administered insulin to correct eating disorders and metabolic and hormonal dysfunctions developing under conditions of experimental diabetes mellitus and metabolic syndrome. In studies involving healthy volunteers, various effects of intranasally administered insulin were shown, including effects on cognitive function, eating behavior and weight loss, and the gender specificity of its action was found. In the course of numerous studies of intranasally administered insulin in animal models of diabetes mellitus, not only stabilization of carbohydrate homeostasis was shown, but also a positive effect in the form of restoration of the functional activity of insulin signaling pathways in the hypothalamus and other parts of the brain. We have presented and analyzed data on the systemic effects of intranasally administered insulin in rodents with experimental models of diabetes mellitus, as well as in healthy individuals.

PATHOGENESIS OF ENDOTHELIAL DYSFUNCTION IN DIABETIC RETINOPATHY DURING STREPTOZOTOCIN-INDUCED DIABETES MELLITUS

One of the main diabetes complications that can lead to the disability of patients is diabetic retinopathy. The purpose of the study was to investigate endothelial dysfunction markers in modelled diabetic retinopathy. Material and methods. The experiment was conducted on male rats of the Wistar line, weighing 180-220 grams, up to 3 months of age (inclusive). During the experiment, the animals were divided into two groups. The 1st group included 20 intact animals; the 2nd group had 60 animals with modelled diabetes mellitus and non-proliferative diabetic retinopathy. Results and discussion. Having studied endothelial nitric oxide synthase, we have found out significant differences (p <0.001) when comparing the findings obtained in the 2nd group with the findings of the intact animals. The 2nd group rats were simulated with diabetic retinopathy without following correction. We also observed the decreasing dynamics of this index. For a more detailed study of the functional state of the endothelium and its disruption, we selected the von Willebrand factor, which is one of the common markers showing the damage to the functional state of the endothelium. In the group with simulated pathology, the level of the investigated marker increased compared with intact animals (p <0.001). There was an increase in endothelin-1 level (p <0.001) in the laboratory rats with modelled diabetic retinopathy. Conclusion. The study results have proven that our experimental model of diabetes mellitus and one of its complications, diabetic retinopathy is accompanied by the development of endothelial dysfunction. There has been found as increase in the von Willebrand factor in the modelled pathological process. We have detected an increase in endothelin-1, a marker of vasoconstriction and endothelial dysfunction, 30 days since the beginning of the experiment. Inhibition of endothelial NO synthase activity indicates an impairment of the physiological NO synthesis.

СТРУКТУРНІ ОСОБЛИВОСТІ СЛИЗОВОЇ ОБОЛОНКИ ДВАНАДЦЯТИПАЛОЇ КИШКИ ЩУРІВ ПРИ ОПІКОВІЙ ТРАВМІ ШКІРИ ЗА УМОВ ЕКСПЕРИМЕНТАЛЬНОГО СТРЕПТОЗОТОЦИНІНДУКОВАНОГО ЦУКРОВОГО ДІАБЕТУ

Робота присвячена вивченню структурних особливостей слизової оболонкидванадцятипалої кишки при опіковій травмі шкіри за умов експериментальногострептозотоциніндукованого цукрового діабету. Дослідження здійснене на лабораторнихбілих статевозрілих щурах-самцях масою 180-210 г. Групу контролю склали 21 інтактнатварина, І експериментальну групу склали 21 щур з експериментальною опіковою травмоюшкіри, ІІ експериментальну групу склали 21 щур без опіку шкіри з експериментальнимстрептозотоциніндукованим діабетом, ІІІ експериментальну групу склали 21 щур з опікомшкіри та експериментальним стрептозотоциніндукованим діабетом. Модельекспериментального цукрового діабету відтворювали шляхом введення щурамстрептозотоцину внутрішньоочеревенно одноразово в дозі 50 мг/кг. Термічне опіковепошкодження шкіри у щурів відповідало II – А-Б ступеню – дермального поверхневого опіку (застарою класифікацією III – А ступінь) загальною площею 21-23% поверхні тіла з розвиткомопікового шоку. Для морфологічних досліджень було забрано відділ дванадцятипалої кишки,фрагменти якого обробляли загальноприйнятими методами світлової та електронноїмікроскопії. Основними критеріями оцінки пошкодження слизової оболонки дванадцятипалоїкишки стали результати дослідження щодо порівняння гістологічних та ультраструктурнихданих в динамиці через 7, 14, та 21 добу після опіку шкіри. Результати проведених дослідженьпоказали зменшення кількості щільних контактів в інтестінальному епітеліальному бар’єріслизової оболонки дванадцятипалої кишки щурів першої та третьої експериментальних групта втрату упорядкованості (набуття певної хаотичності) їхньої локалізації у міру збільшеннячасу після опікової травми. В інтестінальному епітеліальному бар’єрі з’являються дефекти,які є потенційними шляхами парацелюлярної транслокації патогенного вмістудванадцятипалої кишки. Не виключно, що частина цього інтестінального патогенного вмістуможе бути транслокована і через частково пошкоджені клітин. Свідченням останнього євиявлена наявність мікробних тіл в цитоплазмі клітин з частково зруйнованою плазмолемою(але збереженими органелами та ядром). Адаптивним механізмом щодо забезпечення репараціїушкоджених ентероцитів є селективна автофагія, яка виступає чинником рециклізаціїматеріалу зруйнованих органел і цитоплазматичного матриксу, спрямованого, в першу чергу,на підтримку життєздатності клітин. Ініціація автофагії асоційована з розвитком вентероцитах стресу ендоплазматичного ретикулуму (ER-стресу). В ентероцитахдванадцятипалої кишки щурів третьої експериментальної групи ER-стрес відбуваєтьсянастільки стрімко і супроводжується неухильним поширенням процесів деструкції в клітині,що механізми автофагії не встигають спрацьовувати і більшість клітин гине. Таким чином,відсутність автофагійної реакції є маркером несприятливого спрямування перебігупісляопікових структурних змін в ентероцитах.