Study of Hypoglycemic Activity of Subetta and Rosiglitazone on the Model of Streptozotocin-Induced Diabetes Mellitus in Rats

Kheyfets, I. A.; Spasov, A. A.; Воронкова, М П; Dugina, J. L.; Epstein, O. I.

doi:10.1007/s10517-012-1641-8

Cited by 11 publications

(21 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Previously, Subetta demonstrated the ability to reduce hyperglycemia and improve glucose tolerance in various experimental models of diabetes mellitus and its effects were similar to that of rosiglitazone [14, 15]. Subetta was given by oral gavage, when it was studied in vivo but in the current study the direct action of Subetta on mature human adipocytes was estimated in vitro .…”

Section: Resultsmentioning

confidence: 92%

“…In two DM animal models, streptozotocin-induced DM [14] and spontaneous T2D in Goto Kakizaki rats [15], Subetta showed antidiabetic effects similar to that of rosiglitazone. Additionally, Subetta has shown promising results in its first clinical use in both type 1 diabetes (T1D) patients with poor glycemic control receiving intensive insulinotherapy and T2D patients receiving metformin/combination of basal insulin with metformin (unpublished data).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Subetta Treatment Increases Adiponectin Secretion by Mature Human AdipocytesIn Vitro

Nicoll

Gorbunov²,

Тарасов³

et al. 2013

International Journal of Endocrinology

View full text Add to dashboard Cite

Purpose. To investigate the mechanism of action in peripheral tissues of novel complex drug containing release-active dilutions of antibodies to the beta subunit of the insulin receptor and antibodies to endothelial nitric oxide synthase (Subetta), which has shown efficacy in animal models of diabetes. Methods. Human mature adipocytes were incubated either with Subetta, with one of negative controls (placebo or vehicle), with one of nonspecific controls (release-active dilutions of antibodies to cannabinoid receptor type I or release-active dilutions of rabbit nonimmune serum), or with dimethyl sulfoxide (DMSO) at 37°C in a humidified incubator at 5% CO2 for three days. Rosiglitazone was used as reference drug. Secretion of adiponectin was measured by quantitative enzyme-linked immunosorbent assay (ELISA). Results. Only Subetta significantly stimulates adiponectin production by mature human adipocytes. Nonspecific controls did not significantly affect adiponectin secretion, resulting in adiponectin levels comparable to background values of the negative controls and DMSO. Conclusion. Increasing adiponectin production in absence of insulin by Subetta probably via modulating effect on the beta subunit of the insulin receptor might serve as one of the mechanisms of the antidiabetic effect of this drug. These in vitro results give first insight on possible mechanism of action of Subetta and serve as a background for further studies.

show abstract

Section: Resultsmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Subetta Treatment Increases Adiponectin Secretion by Mature Human AdipocytesIn Vitro

Nicoll

Gorbunov²,

Тарасов³

et al. 2013

International Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…The third group (PGK3 group) was given Subetta (5 mL/kg body weight) once a day, as a water solution (2.5 mL/kg body weight of RAD of Abs to β -InsR + 2.5 mL/kg body weight of RAD of Abs to eNOS). The dose of Subetta was the same as that used in the previous study in rats with streptozotocin-induced diabetes (5 mL/kg body weight), where drug showed significant antihyperglycemic efficacy [7]. So, Subetta contains RAD of Abs to β -InsR and RAD of Abs to eNOS.…”

Section: Methodsmentioning

confidence: 99%

“…In experimental model of streptozotocin-induced diabetes Subetta showed pronounced antihyperglycemic activity, which is comparable to that of the reference drug Rosiglitazone: Subetta decreases high plasma levels of glucose, urine levels of ketone bodies and improves glucose uptake in peripheral tissues [7]. Toxicological studies proved a high safety of the drug.…”

Section: Introductionmentioning

confidence: 93%

The Novel Oral Drug Subetta Exerts an Antidiabetic Effect in the Diabetic Goto-Kakizaki Rat: Comparison with Rosiglitazone

Bailbé

Philippe

Gorbunov³

et al. 2013

Journal of Diabetes Research

View full text Add to dashboard Cite

The aim of the present study was to evaluate the potential antidiabetic effects of two-component drug Subetta and its components (release-active dilutions of antibodies to β-subunit insulin receptor (RAD of Abs to β-InsR) and to endothelial nitric oxide synthase (RAD of Abs to eNOS)) in Goto-Kakizaki (Paris colony) (GK/Par) diabetic rats. Subetta was administered orally for 28 days once daily (5 mL/kg) and compared to its two components (2.5 mL/kg), Rosiglitazone (5 mg/kg), and vehicle (5 mL water/kg). At day 28, fasting plasma glucose levels were significantly decreased only in Subetta and Rosiglitazone groups as compared to vehicle (P < 0.01): 147 ± 4 mg/dL and 145 ± 4 mg/dL and 165 ± 4 mg/dL, respectively. The data of glucose tolerance test showed that Subetta and RAD of Abs to β-InsR (similar to Rosiglitazone) prevented significantly (P < 0.01) the age-related spontaneous deterioration of glucose tolerance as seen in the control group. Subetta and RAD of Abs to β-InsR did not significantly modify the glucose-induced insulin secretion. Chronic administration of Subetta and RAD of Abs to β-InsR improves glucose control, to an extent similar to that of Rosiglitazone. We hypothesize that Subetta and RAD of Abs to β-InsR mostly act via an insulin-sensitizing effect upon target tissues.

show abstract

“…Кроме того, препарат увеличивает чувствительность тка-ней к действию инсулина, стимулируя инсулин-индуцированный захват глюкозы мышечными клетками человека in vitro [46]. На моделях СД1 и СД2 препарат продемонстрировал антигипергли-кемическую активность: значимо снижал повы-шенное содержание глюкозы в плазме, не вызывая гипогликемии, а также восстанавливал нарушен-ную толерантность тканей к глюкозе [47,48]. Пер-вые клинические данные у пациентов с СД2, полу-чающих либо метформин, либо базальный инсулин в сочетании с метформином, показали, что вклю-чение субетты в терапию приводит к значимому снижению уровня глюкозы в плазме натощак и гликированного гемоглобина, оказывает нормали-зующее действие на суточный профиль гликемии, а также существенно снижает уровень общего хо-лестерина в плазме [49].…”

Section: активация и потенцирование инсулиновой сигна-лизации улучшеunclassified

Promising pharmacological targets for the treatment of the diseases associated with the impaired insulin receptor signaling pathway

Gorbunov

Brigadirova

Качаева

et al. 2015

Probl Endokrinol (Mosk)

View full text Add to dashboard Cite

ОБЗОРЫСахарный диабет (СД) занимает одно из первых мест в мире среди наиболее распространенных хро-нических заболеваний. В ряд социально значимых заболеваний СД ставят такие его особенности, как большая частота встречаемости, высокий риск ин-валидизации и смертности больных. В 2013 г., по данным Международной диабетической федерации, численность больных СД в мире составила 386 млн человек. Учитывая темпы распространения заболе-вания, согласно прогнозам экспертов ВОЗ, число пациентов с диагнозом СД достигнет к 2035 г. 592 млн человек в основном за счет больных СД 2-го типа (СД2) [1]. По данным Минздрава России, уро-вень инвалидизации по причине СД составляет 2,1 случая на 100 тыс. населения [2].СД представляет собой гетерогенную группу ме-таболических расстройств, которые характеризуют-ся общим симптомом -хронической гиперглике-мией, а также абсолютным или относительным де-фицитом продукции инсулина, либо его действия [3]. СД 1-го типа возникает из-за недостаточной продукции инсулина вследствие потери функцио- Diabetes mellitus (DM) is one of the most widespread chronic diseases in the world. In DM type 2, peripheral tissues demonstrate strong resistance to endogenous insulin (insulin resistance) which is caused by impaired ability of the hormone to stimulate glucose uptake in target cells (muscle, adipose or brain tissue, liver, etc.) and to reduce blood glucose level. Research data suggest that all mentioned reasons are most likely to be based on a disruption of signal transduction from insulin receptor (IR) into insulin-dependent intracellular signaling cascades. Contemporary DM treatment strategy is aimed at the maintenance of optimal blood glucose level by improving insulin production and increasing insulin sensitivity of tissue as well as prevention of macro-and microvascular complications and decrease of their intensity. At the same time, the search for new targets for creation of innovative anti-diabetic compounds can be considered a promising task due to the optimization of existing approaches and development of the novel ones taking into account results of the latest research into DM etiology and pathogenesis. A special position among possible targets is occupied by insulin receptor (IR) and IR-associated signaling pathways. Belonging to tyrosine kinase receptor family, IR has been actively studied during the last decades. This review considers in particular the IR structure and functioning of receptor-associated signaling pathways. The paper contains data on novel ligand-mimetics and IR sensitizers as well as other molecules, which affect different components of IR-associated signaling pathways, thus exerting significant antidiabetic effect. Action of these compounds is aimed at improvement of basic metabolic disorders resulting in hyperglycemia and is mainly carried out due to the following effects: activation and potentiation of insulin signaling, increase of insulin sensitivity of peripheral tissues; recovery of insulin secretion physiological mechanisms; reduction of glucose production in liver.

show abstract

Study of Hypoglycemic Activity of Subetta and Rosiglitazone on the Model of Streptozotocin-Induced Diabetes Mellitus in Rats

Cited by 11 publications

References 4 publications

Subetta Treatment Increases Adiponectin Secretion by Mature Human AdipocytesIn Vitro

Subetta Treatment Increases Adiponectin Secretion by Mature Human AdipocytesIn Vitro

The Novel Oral Drug Subetta Exerts an Antidiabetic Effect in the Diabetic Goto-Kakizaki Rat: Comparison with Rosiglitazone

Promising pharmacological targets for the treatment of the diseases associated with the impaired insulin receptor signaling pathway

Contact Info

Product

Resources

About