The failure of the fight against obesity makes us turn to new goals in its treatment. Now, brown adipose tissue has attracted attention as a promising target for the treatment of obesity and associated metabolic disorders such as insulin resistance, dyslipidemia, and glucose tolerance disorders. Meanwhile, the expansion of our knowledge has led to awareness about two rather different subtypes: classic brown and beige (inducible brown) adipose tissue. These subtypes have different origin, differences in the expression of individual genes but also a lot in common. Both tissues are thermogenic, which means that, by increasing energy consumption, they can improve their balance with excess intake. Both tissues are activated in response to specific inducers (cold, beta-adrenergic receptor activation, certain food and drugs), but beige adipose tissue transdifferentiates back into white adipose tissue after the cessation of inducing action, while classic brown adipose tissue persists, but its activity decreases. In this review, we attempted to understand whether there are differences in the effects of different groups of thermogenesis-affecting drugs on these tissues. The analysis showed that this area of research is rather sparse and requires close attention in further studies.

Effects of glucagon-like peptide 1 analogs in combination with insulin on myocardial infarct size in rats with type 2 diabetes mellitus

Objective: Sulfonylureas and dipeptidyl peptidase‐4 inhibitors have a multidirectional effect on pancreatic cells. We aimed to evaluate the effects of these drugs on β‐ and α‐cells in rats aged 12 months with type 2 diabetes mellitus when administered in combination with various sulfonylureas.Methods: Streptozotocin‐nicotinamide induced type 2 diabetes mellitus was induced in rats aged 12 months. Animals received the sulfonylureas gliclazide or glibenclamide for 24 weeks alone or in combination with the dipeptidyl peptidase‐4 inhibitor vildagliptin or vildagliptin monotherapy. Blood glucose and animal weights were measured before and during the experiment. The oral glucose tolerance test was conducted before therapy initiation. Immunohistochemical analyses were conducted after the end of the experiment using glucagon and insulin antibodies. The total volumes of α and β cells were estimated in relation to the volume of the pancreatic islets.Results: The total volumes of β‐cells did not differ between the sulfonylurea group and the untreated type 2 diabetes mellitus group. The addition of dipeptidyl peptidase‐4 inhibitors to sulfonylureas normalized the total volumes of β cells. The total volumes of α‐cells in the gliclazide group and combination of gliclazide with dipeptidyl peptidase‐4 inhibitor was comparable to that in the control group of intact animals, in contrast with the glibenclamide group.Conclusion: The combination of vildagliptin to both sulfonylureas contributed to the normalisation of β‐cells number. Normalisation of the total volumes of α‐cells was observed with gliclazide therapy and combination of gliclazide with dipeptidyl peptidase‐4 inhibitor.

Purpose: evaluate the eff ects of DPP4i on fasting and postprandial insulin and glucagon secretion by examining basal secretion and response to food loading.Materials and methods: patients (n = 54) were divided into treatment groups: long-term (more than a year) therapy with iDPP4 with Metformin, Metformin + sulfonylurea, fi rst-time therapy with iDPP4. Biochemical parameters, levels of insulin, glucagon, C-peptide before and aft er a standard breakfast were measured. Th e HOMA IR and HOMA β indices were calculated. Results: we obtained a signifi cant diff erence in fasting glucagon and insulin levels between the iDPP4 over a year and Metformin + SM groups. In addition, insulin levels before and aft er standard breakfast, C-peptide aft er standard breakfast, and fasting glucagon decreased aft er 6 months of fi rst-time DPP4 therapy.Summary: the data obtained indicate the ability of iDPP4 to positively infl uence the two earliest and most signifi cant links in the pathogenesis of type 2 diabetes.

Актуальность. Инсулинотерапия сопряжена с высоким риском гипогликемии, высокой вариабельностью гликемии. Поэтому терапия периинфарктных пациентов с сахарным диабетом 2 типа (СД2) аналогами глюкагоноподобного пептида-1 (аГПП-1), способными уменьшить вариабельность гликемии и риск гипогликемий, становится актуальной. Цель. Изучение эффектов комбинированного применения аГПП-1 и инсулинотерапии на модели острого инфаркта миокарда (ОИМ) у крыс и на уровень маркеров повреждения миокарда, натрийуретического пептида типа В (BNP), динамику эхокардиографических показателей (ЭхоКГ) и показатели гликемии у пациентов с СД2 и ОИМ. Материалы и методы. В эксперименте моделировался неонатальный стрептозотоциновый сахарный диабет (СД). Группы животных формировались в зависимости от времени начала терапии инсулином, аГПП-1 (эксенатидом) или комбинированной терапии — до или после ОИМ. Проводилась морфологическая оценка очага ишемии и некроза и оценивалась вариабельность гликемии. В клинической части формировались 2 группы пациентов с СД2 и ОИМ. Первая группа получала стандартную инсулинотерапию, вторая группа — комбинированную терапию инсулином и аГПП-1. Оценивались параметры гликемии, маркеры повреждения миокарда, BNP, динамика ЭхоКГ. Результаты. Наблюдалось уменьшение зоны некроза, вариабельности гликемии в группе комбинированной терапии в эксперименте. Уровни тропонина I и креатинфосфокиназы МВ исходно существенно не отличались во всех группах пациентов. У пациентов с аГПП-1 отмечалось снижение вариабельности гликемии, положительная динамика как уровня рго-BNP, так и фракции выброса (ФВ) во время наблюдения. Заключение. Наиболее выраженный положительный эффект на течение ОИМ аГПП-1 оказывает при введении до начала реперфузии. Добавление аГПП-1 у пациентов не оказало влияния на динамику маркеров повреждения миокарда, но уменьшало вариабельность гликемии, улучшало динамику лабораторных показателей, отражающих выраженность сердечной недостаточности.

Introduction. Insulin therapy used during acute myocardial infarction (AMI) is associated with a high risk of hypoglycemia and high glycemic variability. Therefore, the search for optimal therapeutic approaches which affect both cardioprotection and glycemic correction is relevant. It is known that agonists of glucagon-like peptide-1 (aGLP1) exhibit a protective effect on the myocardium and are involved in the normalization of carbohydrate metabolism. The combined use of аGLP1 exenatide and insulin can be more effective and safe but not insufficiently studied.The aim of this study was the comparative investigation of the effect of exenatide, insulin, and their combination on the volume of myocardial damage and the level of glycemia in the myocardial ischemia/reperfusion (I/RP) model in rats with experimental diabetes mellitus (DM2).Materials and methods. Neonatal streptozotocin diabetes was modeled in male Wistar rats on the 4th–5th day of life. At the age of 3 months, I/RP was fulfilled in animals with confirmed hyperglycemia. Experimental groups were formed depending on the time of therapy with insulin, exenatide, or their combination; before or after ischemia. Ischemia lasted for 40 min, while reperfusion was 120 min. The size of the myocardium necrosis zone and the changes in glycemia level and its variability were determined.Results. Insulin reduced glycemia, but it increased glycemic variability by 60 % and caused hypoglycemia in 32–37 % of animals. Exenatide reduced blood glucose concentration to the level of fasting glycemia and glycemic variability by 1.5–2 times compared with insulin. Exenatide given before ischemia reduced the area of necrosis by 2.2 times. The combined use of insulin and exenatide was accompanied by the absence of hypoglycemia and a decrease in the necrosis zone by 3.2 times compared to the control.Conclusion. The combined use of aGLP1exenatide and insulin in experimental conditions of I/RP+DM2 is the most effective and safe. This makes promising their joint use in patients with DM2, both at high risk of AMI and those undergoing AMI.