Antidiabetic Effects of Bisamide Derivative of Dicarboxylic Acid in Metabolic Disorders

Angelina Vladimirovna Pakhomova,Edgar Sergeevich Pan,Wolf-Dieter Grimm,Viacheslav Yur’Evich Kravtsov,Olga Victorovna Pershina,Natalia Nicolaevna Ermakova,Vyacheslav Andreevich Krupin,Vladimir Evgenievich Nebolsin,Darius Widera,Olga Evgenevna Vaizova,Sergey Georgievich Morozov,Aslan Amirkhanovich Kubatiev,Lubov Alexandrovna Sandrikina,Alexander Mikhaylovich Dygai,Sergey Alexandrovich Afanasiev,Evgenii Germanovich Skurikhin

doi:10.3390/ijms21030991

Abstract

In clinical practice, the metabolic syndrome can lead to multiple complications, including diabetes. It remains unclear which component of the metabolic syndrome (obesity, inflammation, hyperglycemia, or insulin resistance) has the strongest inhibitory effect on stem cells involved in beta cell regeneration. This makes it challenging to develop effective treatment options for complications such as diabetes. In our study, experiments were performed on male C57BL/6 mice where metabolic disorders have been introduced experimentally by a combination of streptozotocin-treatment and a high-fat diet. We evaluated the biological effects of Bisamide Derivative of Dicarboxylic Acid (BDDA) and its impact on pancreatic stem cells in vivo. To assess the impact of BDDA, we applied a combination of histological and biochemical methods along with a cytometric analysis of stem cell and progenitor cell markers. We show that in mice with metabolic disorders, BDDA has a positive effect on lipid and glucose metabolism. The pancreatic restoration was associated with a decrease of the inhibitory effects of inflammation and obesity factors on pancreatic stem cells. Our data shows that BDDA increases the number of pancreatic stem cells. Thus, BDDA could be used as a new compound for treating complication of the metabolic syndrome such as diabetes.

Highlights

By definition of the International Association of Diabetes, metabolic syndrome (MS) is a combination of abdominal obesity, insulin resistance, hyperglycemia, dyslipidemia, arterial hypertension, disruption the hemostatic system, and chronic subclinical inflammation [1,2]
Based on the findings from our previous studies suggesting that Bisamide Derivative of Dicarboxylic Acid (BDDA) has regenerative properties [16], we aimed to assess the efficacy of BDDA in metabolic disorders and their complications such as diabetes in a mouse model of metabolic disorders (MD)
Streptozotocin and high-fat diet caused an increase in the concentration of triglycerides (TG) and very low-density lipoproteins (VLDL) in the serum of male C57BL/6 mice compared to the intact control on d70, with an increase in the atherogenic index (Figure 1)

Summary

Introduction

By definition of the International Association of Diabetes, metabolic syndrome (MS) is a combination of abdominal obesity, insulin resistance, hyperglycemia, dyslipidemia, arterial hypertension, disruption the hemostatic system, and chronic subclinical inflammation [1,2]. A major concern is a steady increase in the frequency of MS among adolescents and young people [5]. The clinical significance of MS lies in its complications, especially in combination with other diseases where it accelerates their development and progression [7,8]. In this context, MS can lead to serious complications such as cardiovascular disease, type 2 diabetes, osteoarthritis, sleep apnea, non-alcoholic steatohepatitis, respiratory problems, malignant tumors, and type 2 diabetes [9,10,11,12,13]. There is a linear relationship between the body mass index (BMI) and mortality from coronary heart disease (CHD), stroke, and diabetes [14,15]

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