The Role of Circulating miRNAs in IsletCell Crosstalks
Year: 2026
Type: dissertation
Abstract: The Diabetes Atlas, published by the International Diabetes Federation IDF (2025), reported there arenearly 589 million people living with diabetes mellitus (DM), which is an international public healthproblem. The majority is people living with type 2 diabetes(T2D), a disease caused by insulin resistanceand impaired insulin secretion. We were interested to investigate potential crosstalk throughmicroRNAs (miRNAs) inside extracellular vesicles (EVs) between pancreatic beta cells and othermetabolic tissues such as the liver using the beta cell line MIN6. Therefore, the aim of this thesis wasto investigate effects on glucolipotoxicity and the expression of key miRNAs under these conditions inthe MIN6 cells. Furthermore, we aimed to isolate EVs from the MIN6 cells medium after culture. Wefound that MIN6 cells operate best after being cultured in 25 mM glucose. Thus, glucotoxicity seemednot harmful to the MIN6 cells as compared to primary beta cells. Culture at 25 mM glucose togetherwith 0.5 mM palmitate reduced insulin content and thereby glucose stimulated insulin secretion (GSIS)by ~50%. Likewise, when insulin release was stimulated by high potassium (K+) solution to specificallyaffect exocytosis similar response was observed. Culture of MIN6 cells in palmitate further increasedthe expression of several miRNAs, earlier shown to negatively impact insulin secretion. These includedmiR-152, miR-130a, and miR-130b. Bioinformatic analysis determined potential predicted targets ofthese three miRNAs and two was found as interesting candidates. Optimization of EVs is still ongoing.In conclusion, the MIN6 cells show reduced insulin secretion and changes in miRNA expression afterlipotoxic treatment and will therefore serve as a good model for further investigations of EVs releasedfrom insulin secretion cells and their role in T2D development.
Author: Mahadevaiah, Meghana Omprakash
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7165426513