Role of Progenitor Cells in Metabolic Diseases Associated with Insulin Resistance

Oktayoğlu S.

I. International Advances in Molecular Biology Congress, İstanbul, Turkey, 19 - 22 September 2022

  • Publication Type: Conference Paper / Summary Text
  • City: İstanbul
  • Country: Turkey
  • Istanbul University Affiliated: Yes


Adult stem/progenitor cells provide the continuity of the cell population in the organs and regeneration following tissue damage. Although these cells have a strong defense mechanism against environmental factors, it is known that in the presence of long-term and high stimuli or factors such as ageing, the progenitor cell pool decreases and their functions are lost. In this respect, progenitor cells play an important role in organ damage and even organ failures that occur with chronological or cellular ageing. Over the last decades, the progressive ageing which has occurred in most populations have been paralleled by a global epidemic of obesity and its related metabolic disorders, primarily, type 2 diabetes. It is known that insulin resistance, which is the common point of obesity, type 2 diabetes and metabolic syndrome, plays a central role in the development of many diseases such as Alzheimer's disease, nonalcoholic fatty liver/pancreas disease and even sarcopenia. The effects of insulin resistance in the development process of these diseases, which are associated with a decrease in the progenitor cell pool and deterioration in its function, is a very new research topic. By determining the metabolic, molecular and phenotypic changes of organ-specific progenitor cells that develop insulin resistance, new targets can be determined for the early diagnosis and treatment of these diseases, and different perspectives can be developed in these areas.

Our findings demonstrate that when insulin and leptin resistance develop together in rat pancreatic islet derived-progenitor cells, beta-cell differentiation, which observed during the compensation step of type 2 diabetes development, increases markedly via β-catenin and Tub.  Based on this finding, we propose new therapeutic agents that inhibit AKT/GSK-3β/β-catenin and in particular Tub may help prevent the development or retard the progression of type 2 diabetes.  Moreover, long-term saturated fatty acid overexposure, which known as one of the factors of insulin resistance, may cause intrapancreatic fat accumulation by inducing differentiation of duct cells into adipocytes. In this study we propose that miR-375 may have the potential to be a new target in the treatment of Type 2 diabetes, and nonalcoholic fatty pancreas disease due to its role in the adipogenesis of duct cells. In our other related study we showed that metformin, a drug used in the treatment of insulin resistance, significantly increased beta-cell differentiation. The mechanism involves suppression of the sweet taste signal's molecules T1R3, PLCβ2, cytoplasmic Ca+2, and AKT in addition to the direct effect of metformin on mitochondria. These findings are very important in terms of determining that metformin stimulates the mitochondrial remodeling and the differentiation of pancreatic islet derived-progenitor cells to beta-cells and thus it may contribute to the compensation step. Another work of our team demonstrated that long-term aspartame exposure, which contributes to the development of insulin resistance, increases cancer stem cell population and tumor cell aggressiveness through p21, NICD, GLI1. These studies and the findings of our ongoing projects show that changes in progenitor cell function play an important role in metabolic diseases associated with insulin resistance.