Akademik Veri Yönetim Sistemi
I. International Advances in Molecular Biology Congress, İstanbul, Türkiye, 19 - 22 Eylül 2022
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.