The effect of gadolinium additives on the morphology, phase composition, and catalytic properties of MoVSbNbGdOx/SiO2 catalysts in the oxidative dehydrogenation of ethane to ethylene (ODE) is studied. It is shown that gadolinium concentration has a significant effect on the catalytic properties. At an optimum gadolinium content (Gd/Mo = 0.01–0.015), an increase in catalytic activity and ethylene selectivity is observed: at a temperature of 400°C, the ethylene yield achieves 72

In obesity, the insulin and leptin pathways in the brain and peripheral tissues are attenuated. In the brain, one of the reasons for this is the impaired transport of insulin and leptin across the blood–brain barrier (BBB), as indicated by changes in the ratio of their concentrations in the blood flow and different brain structures. However, neither these changes under obesity nor the effect of pharmacological agents on them are almost unstudied. The aim of the work was to assess insulin and leptin levels in the brain structures (hypothalamus, cerebellum) and their correlation with those in the blood of male rats with obesity caused by a long-term combined high-calorie diet, as well as to study the effect of a four-week treatment of obese rats with metformin (200 mg/kg/day), bromocriptine (0.6 mg/rat/day), intranasal insulin (I-I) (0.5 IU/rat/day), as well as their two-week treatment with PI4, a protein phosphotyrosine phosphatase 1B (PTP1B) inhibitor (10 mg/kg/day), on these parameters. It was shown that in obesity accompanied by with hyperinsulinemia and hyperleptinemia, insulin and leptin transport to the hypothalamus and cerebellum across the BBB is attenuated, leading to a significant increase in concentration ratios of these hormones in the blood and brain structures. Metformin treatment not only normalized metabolic parameters and sensitivity to insulin and leptin, but also completely restored their levels in the brain structures. Bromocriptine/I-I treatment was less effective. PI4 treatment of obese rats caused a significant loss in their body and adipose tissue weight, reduced their food intake, improved the metabolic parameters, and increased insulin and leptin sensitivity. The PTP1B inhibitor PI4 also restored the ratio of insulin and leptin concentrations in the blood and brain structures, but not due to an increase in their brain levels, as with metformin, but as a result of a significant decrease in blood hormone concentrations. Our data indicate that the treatment with drugs having varied chemical structure and mechanisms of action but sharing the ability to improve metabolic and hormonal parameters in obesity leads to normalization of insulin and leptin ratios at the periphery and in the CNS, thus restoring insulin and leptin signaling in the hypothalamus and other brain regions, as well as central insulin- and leptin-mediated regulation of metabolic processes at the periphery.

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.

Дефицит грудного вскармливания в раннем постнатальном периоде может приводить к метаболическим и гормональным нарушениям во взрослом возрасте. Однако исследования влияния голодания в раннем онтогенезе на метаболические и гормональные показатели у старых животных отсутствуют. Практически не изучено влияние такого голодания на функции эндокринной системы. Цель исследования - изучение того, как прерывание лактации у кормящих самок крыс (на 19-21-й день постнатального развития крысят) влияет на метаболические показатели, толерантность к глюкозе, чувствительность к инсулину и гормональный статус гонадной и тиреоидной осей у их потомства, 18-месячных самцов крыс. Ингибирование лактации вызывали с помощью обработки самок крыс бромокриптином (10 мг/кг в сутки). Показано, что старые самцы крыс с частичным лишением грудного вскармливания имеют характерные признаки метаболического синдрома - повышенную массу тела и жировой ткани, нарушенную толерантность к глюкозе, инсулиновую резистентность, гиперлептинемию. У них снижен уровень тестостерона и тиреоидных гормонов, повышен уровень ТТГ, снижены стероидогенный ответ на гонадолиберин и стимулирующий эффект тиролиберина на уровень тироксина. Таким образом, краткосрочная депривация грудного вскармливания, вызванная бромокриптин-индуцированным ингибированием лактации у кормящих самок, приводит к развитию метаболического синдрома и гормональной дисрегуляции репродуктивной и тиреоидной систем у 18-месячных самцов крыс. Breastfeeding deficiency in the early postnatal period can lead to metabolic and hormonal disorders in adulthood. However, there are no studies on the effect of starvation in early ontogeny on metabolic and hormonal parameters in aging animals. The effect of such starvation on the functions of the endocrine system has not been practically studied. The aim of this work was to study how interruption of lactation in lactating female rats (19-21 days of postnatal development of rat pups) affects metabolic parameters, glucose tolerance, insulin sensitivity, and hormonal status of the gonadal and thyroid axes in their offspring, 18-month-old male rats. Inhibition of lactation was induced by treating female rats with bromocriptine (10 mg/kg/day). It has been shown that aging male rats with partial deprivation of breastfeeding have characteristic signs of the metabolic syndrome, such as the increased body weight and adipose tissue, impaired glucose tolerance, insulin resistance, and hyperleptinemia. They have reduced levels of testosterone and thyroid hormones, increased levels of thyroid-stimulating hormone, reduced steroidogenic response to gonadoliberin and a decrease in thyroliberin stimulating effect on thyroxine levels. Thus, short-term deprivation of breastfeeding caused by bromocriptine-induced inhibition of lactation in lactating females leads to the development of metabolic syndrome and hormonal dysregulation of the reproductive and thyroid systems in 18-month-old male rats.

Temporary cessation or restriction of breastfeeding can lead to metabolic disorders in adulthood. However, data on the effect of fasting in the early postnatal period on the functions of the endocrine system in adulthood are rare and contradictory. Approaches for the correction of metabolic and hormonal disorders caused by premature cessation of breastfeeding have not been developed yet. The aim of the work was to study the metabolic and hormonal parameters and changes in the hormonal status of the gonadal and thyroid systems in 10-month-old male rats with interruption of breastfeeding on days P19-P21, as well as to evaluate the restorative effect on them of four weeks of treatment with intranasal insulin (II) administered in the postnatal period (P28-P55) or in adulthood (P183-P210). Lactation interruption has been induced by treatment of lactating females with bromocriptine (10 mg/day/rat, P19-P21). Male rats with temporary cessation of breastfeeding developed characteristic signs of the metabolic syndrome (obesity, dyslipidemia, impaired glucose tolerance, hyperleptinemia), decreased levels of testosterone and thyroid hormones (fT4, tT3) and weakened the synthesis of testosterone and thyroxine, stimulated respectively by GnRH and thyroliberin. This was due to a decrease in the sensitivity of the testes to luteinizing hormone (LH) and the thyroid gland to thyroid-stimulating hormone (TSH). Treatment with II in early ontogenesis reduced body weight and fat, improved lipid profile, sensitivity to insulin, leptin, LH and TSH, restored the levels of testosterone and thyroid hormones and their stimulation by releasing factors. Treatment with II in adulthood normalized the levels of testosterone, thyroid hormones, their stimulation by releasing factors, but had a little effect on metabolic and hormonal parameters. The obtained data point to a wide range of metabolic and hormonal disorders in adult male rats with the “neonatal” model of metabolic syndrome and to the effectiveness of various strategies for their correction using long-term II treatment.

Type 2 diabetes mellitus (DM2) is characterised by changes in brain signalling systems, including those regulated by insulin. Intranasally administered insulin (II) can be used to restore brain insulin signalling. The effectiveness of II, as we have shown earlier in DM1 and insulin-deficient DM2, increases when combined with intranasally administered C-peptide (IC). The aim of this work was to study the effect of a 9-day treatment of rats with diet-induced DM2, obesity and hyperinsulinemia with II (0.5 IU/rat/day) and combined II and IC (36 μg/rat/day) on rats' metabolic parameters, basal and glucose-stimulated levels of insulin, adipokines, glucagon-like peptide-1 and ghrelin, hormonal status of the thyroid and gonadal systems, intrahypothalamic insulin and leptin levels, and expression of hypothalamic genes encoding receptors and nutritional factors. II monotherapy normalised hypothalamic insulin levels lowered in DM2, improved glucose homeostasis, thyroid status and insulin, leptin and incretin responses to glucose, restored the expression of hypothalamic proopiomelanocortin and M4-melanocortin receptor genes responsible for reducing appetite, and reduced the gene expression of orexigenic neuropeptide Y. The combined use of II and IC did not improve the effect of II. IC monotherapy was ineffective and even worsened subject metabolic parameters. Thus, in DM2 rats with hyperinsulinemia, II improved metabolic and hormonal parameters. This is due to normalisation of the brain insulin levels that had been reduced as a result of weaker receptor-mediated transport of insulin across the blood-brain barrier. IC, however, was ineffective, including in combination with II.

In type 2 diabetes mellitus (T2DM), the functions of the brain insulin system are impaired, which is associated with a decrease in insulin transport across the blood-brain barrier due to insulin resistance. To restore insulin deficiency in the brain, intranasally administered insulin (II) can be used, and its effect can be enhanced by intranasal administration of C-peptide (ICP). The aim of this work is to study the effect of ten-day treatment of male Wistar rats with hyperinsulinemic and normoinsulinemic T2DM with II (20 µg/rat/day), ICP (36 µg/rat/day) or II+ICP on metabolic and hormonal indices. Hyperinsulinemic T2DM was induced by a 3-month high-fat diet and low-dose streptozotocin treatment of adult rats, while normoinsulinemic T2DM was induced by high-dose streptozotocin treatment of 5-day-old pups. In hyperinsulinemic diabetic rats, II-monotherapy attenuated hyperglycemia, hyperinsulinemia, and hyperleptinemia, and partially restored the blood levels of fT4, tT4, and tT3 reduced in DM2 (p<0.05 as compared to untreated diabetes). ICP was not effective and, in the II+ICP group, it significantly reduced the restorative effects of II. In normoinsulinemic rats with T2DM, II monotherapy increased fT4 and tT3 levels by 31% and 26%, while ICP decreased glucose-stimulated leptin levels by 31% (p<0.05 as compared to untreated diabetes). The use of II+ICP attenuated hyperglycemia, reduced glucose-stimulated insulin levels, and restored the thyroid hormones levels to their control values. Thus, ICP and its combination with II are effective in restoring metabolic and hormonal indices in rats with normoinsulinemic T2DM, but do not improve them in rats with hyperinsulinemic T2DM.

In type 2 diabetes mellitus (DM2), the impaired functions of the brain insulin system are associated with the weakened insulin transport through the blood-brain barrier due to insulin resistance. Insulin deficiency in the brain can be corrected by intranasal administration of insulin (II), whose effect may be enhanced by intranasal administration of C-peptide (ICP). In this work, we study the effect of treating hyperinsulinemic and normoinsulinemic DM2 rats with ICP (36 µg/rat/day), II (20 µg/rat/day) and ICP+II on metabolic and hormonal parameters. In normoinsulinemic DM2, ICP attenuated thyroid hormone deficiency and enhanced the restorative effects of II on glucose, insulin, and leptin sensitivity. In hyperinsulinemic DM2, ICP was ineffective, and its combination with II weakened the restorative effects of II. Thus, ICP and its combination with II are effective in restoring metabolic and hormonal parameters in normoinsulinemic, but not hyperinsulinemic, DM2.

A short-term deprivation of rat pups from breastfeeding in the early postnatal period leads to MS at the age of 4-6 months. However, this neonatal MS model requires optimization and a detailed study into the metabolic and hormonal parameters of adult animals. The aim of the work was to study these parameters in adult male rats deprived of breast milk at the age of 19-21 days, which was achieved by treating lactating females with bromocriptine. Adult male rats showed an increased body weight and adipose tissue, impaired glucose tolerance, insulin resistance, and hyperleptinemia. These animals had reduced levels of testosterone, free thyroxine, and total triiodothyronine, with an increase in the thyroid-stimulating hormone. Thus, a short-term deprivation of breastfeeding in adult rats leads to the development of MS and endocrine dysregulations.

Early weaning (EW) leads to metabolic disorders in adulthood,being one of the causes of metabolic syndrome (MS). However, therange of hormonal disorders in EW has not been studied well enough,and approaches to its correction have not been developed. The aimof this work was to study metabolic and hormonal changes, includingin the hormonal status of the gonadal and thyroid axes, in adult(10-month-old) male rats that were weaned in the early postnatalperiod, as well as to explore the restorative effect of 4-week treatmentwith different doses of metformin (MF), moderate (120 mg/kg/day)and relatively high (250 mg/kg/day), on these changes. Lactationin nursing female rats was interrupted with bromocriptine (10 mg/kg/day)on days 19–21 of lactation. After forced starvation during thisperiod, rat pups were transitioned to a standard diet. At the ageof 10 months, early weaned male rats showed characteristic signsof MS, such as obesity, impaired glucose tolerance, insulin resistance,hyperleptinemia and dyslipidemia. They also had reduced levels oftestosterone, luteinizing hormone (LH), and thyroid hormones, andelevated levels of the thyroid-stimulating hormone (TSH). A 4-weektreatment of adult rats with MF at a moderate dose reduced bodyand fat weight, partially restored metabolic parameters, and completelynormalized testosterone, LH, thyroxine, triiodothyronine and TSHlevels. The treatment with MF at a relatively high dose restoredmetabolic parameters more effectively, normalized leptin and insulinlevels, but had a little effect on hormonal levels of the gonadaland thyroid axes. Thus, long-term treatment of early weaned malerats with a moderate dose of MF improves metabolic parameters andcompletely restores the hormonal status of the gonadal and thyroidaxes, which indicates the promise of using such doses for the correctionof MS and endocrine dysfunctions caused by interrupted or ineffectivebreastfeeding.

MoVNbTe mixed oxide, which is used as a catalyst for the oxidative dehydrogenation of ethane, was investigated by the XPS technique during prolonged treatment with X-rays. This treatment caused a modification of the MoVNbTe oxide surface related to the reduction of V, Mo, and Te species. This behavior is supposed to be related to the interaction of oxide with secondary electrons emitted during X-ray absorption. Firstly, the reduction of Te4+ into Te-0 species, accompanied by the removal of no more than similar to 5% of overall oxygen from the surface/subsurface region, was found during similar to 8.5 h under X-rays. After similar to 28 h of exposure, the significant surface restructuring resulted in a change in the relative amounts of V and Te. This was accompanied by a high degree of surface reduction and the appearance of V3+ species. Under X-rays, an abnormal broadening of Mo 3d spectral lines was observed in contrast to other photoelectron regions. The possible reasons for this phenomenon were discussed. The limit for the amount of lattice oxygen, which might be extracted with the preservation of the pristine surface structure of MoVNbTe oxide, was in the range from 5 to 7%.

Modification by Nd, Mn, Ga, and Ge substantially affect both physicochemical and catalytic properties of MoVNbTeO oxides in the oxidative dehydrogenation of ethane (ODE). The introduction of modifying additives changes the content of the M1 phase, surface acidity, and surface composition. It does not have an infiuence on the state of Mo, V, Nb, and Te on catalyst surface, but it induces surface enrichment (Ga, Mn) or depletion (Ge, Nd) by the modifying element. All of these additives have positive effects on catalytic properties at the M/Mo (M = modifying element) ratio of 0.0075 divided by 0.025. They exhibit an increase of activity and prevent ethylene over-oxidation. The relationship between the rate constant of total ethane transformation and the M1 content confirms that this phase is active in ODE. The correlation between ethylene selectivity and the relative number of intermediate acid sites is revealed, indicating the role of surface acidity on ethylene over-oxidation.

A multicomponent MoVSbNbCeOx/SiO2 oxide catalyst exhibiting high catalytic activity in the oxidative dehydrogenation of ethane to ethylene is synthesized by spray drying of a suspension of aqueous solutions of the precursors and the subsequent heat treatment in He at 350 and 600°C. At a temperature of 400–450°С in a wide ethane conversion range, the catalyst exhibits a fairly high activity and ethylene selectivity. In the presence of this catalyst, the maximum ethylene yield achieves 74% (ethane conversion of 91%, ethylene selectivity of 81.5%); this value significantly exceeds the yield in the presence of Sb-containing catalysts known from the literature. The catalyst exhibits a long-term stable on-stream behavior under reaction medium conditions without any change in the phase composition and a deterioration of the catalytic characteristics. It is shown that the catalytic properties of the synthesized catalyst are comparable to the properties of MoVTeNbOx, which is one of the best catalysts for this process. However, the use of a Te-containing catalyst is limited, because tellurium exhibits a high toxicity and volatility during the synthesis and use of the catalysts. According to X-ray diffraction analysis, the main components of the catalyst are M1 and M2 phases stabilized on a SiO2 surface. The HRTEM data show that a structural feature of the catalyst is the presence of an interface formed by the coherently intergrown crystals of the M1 and M2 phases.