Antidiabetic Effects of Bisamide Derivative of Dicarboxylic Acid in Metabolic Disorders

Int J Mol Sci. 2020 Feb 3;21(3):991. 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.

Keywords: Bisamide Derivative of Dicarboxylic Acid; diabetes; metabolic disorders; regeneration; tissue-specific stem cells.

MeSH terms

  • Amides / chemistry*
  • Animals
  • Cytokines / blood*
  • Dicarboxylic Acids / chemistry*
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacology*
  • Lipids / blood*
  • Male
  • Metabolic Diseases / blood
  • Metabolic Diseases / drug therapy*
  • Metabolic Diseases / pathology
  • Mice
  • Mice, Inbred C57BL

Substances

  • Amides
  • Cytokines
  • Dicarboxylic Acids
  • Hypoglycemic Agents
  • Lipids