islet-like-cells-derived-from-ductal-cell-transplantation-into-rats

Islet-like Cells Derived from Ductal Cell Transplantation into Rats

The use of islet-like cells derived from ductal cells has emerged as a potential approach for treating type 1 diabetes. Diabetic patients have ...

Ankara Medipol University Faculty of Medicine

Endoplasmic reticulum (ER) is very sensitive to the nutritional and energy states of the cells. Disruption of ER homeostasis leads to the accumulation of unfolded/misfolded proteins in the ER lumen, which is defined as ER stress. ER stress triggers the unfolded protein response (UPR). It is suggested that chronic ER stress is associated with obesity and leptin resistance. We investigated the role of ER stress and the effect of the ER stress inhibitor phenylbutyric acid (PBA) of ER stress, in obesity, as well as their impact on leptin signaling. This study involved twenty-four lean and twenty-four leptin-deficient (ob/ob) mice divided into PBA- and vehicle-treated groups. Pancreatic islets were isolated, incubated with leptin for 48 h, and assayed for the expression of CHOP and XBP1s (UPR signaling indicators) and SOCS3 (regulator of leptin signaling) by RT-qPCR. The expression levels of XBP1s and CHOP were markedly increased in the ob/ob controls compared to other groups with and without leptin treatment. No significant differences in the XBP1s and CHOP expression levels were found between the PBA-treated ob/ob and lean mice. SOCS3 expression was significantly upregulated in the PBA-treated ob/ob mice compared to the ob/ob controls after leptin treatment; but no significant difference in the SOCS3 expression was found between the PBA-treated ob/ob and lean mice with and without leptin treatment. Our findings suggested that ER stress plays an important role in the pathology of obesity, while PBA reduces ER stress and may potentially ameliorate leptin signaling.

Chemical Chaperone PBA Attenuates ER Stress and Upregulates SOCS3 Expression as a Regulator of Leptin Signaling.

Regenerative medicine investigates the conversion of pancreatic ductal cells into functional islet cells, offering innovative treatments for conditions such as diabetes. Ductal cells, primarily supporting the pancreas' exocrine functions, can differentiate into various cell types, including islet cells, under specific conditions, opening new avenues in research and therapy. The outlined protocol elaborates on the conversion process, covering ductal cell differentiation induction, and insulin-producing capacity assessment. The primary objective is to address the shortage of insulin-secreting cells for transplantation, thereby advancing diabetes treatment methodologies.

Article	Year
Chemical Chaperone PBA Attenuates ER Stress and Upregulates SOCS3 Expression as a Regulator of Leptin Signaling. Biochemistry. Biokhimiia\| PubMed ID: 33941068	2021
Rat Ductal Cell-Derived Differentiation into Islet-Like Cells. Methods in molecular biology (Clifton, N.J.)\| PubMed ID: 38997537	2025

Gulbahar Boyuk Ozcan

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