Novel METTL3/14 methyltransferase activators for protecting pancreatic beta cells in diabetes mellitus

Julia Konovalova; Huini Li; Maria Lindahl

Novel METTL3/14 methyltransferase activators for protecting pancreatic beta cells in diabetes mellitus

Research output: Conference materials › Poster › peer-review

Abstract

RNA methylation of N6-adenosine (m6A) is a common reversible RNA modification, involved in various biological processes, e.g. RNA stability, splicing, translation. Recent research show that dysregulated m6A mRNA levels in islets is associated with diabetes, suggesting increasing m6A mRNA levels as a valuable target for beta-cell protection.
The aim of this project is to elucidate a) mRNA m6A and their regulating proteins levels in healthy beta-cells and diabetes pathology, and b) the effect of METTL3/14 activator compounds on the proliferation and survival of cytokine- or palmitate treated beta-cells in vitro.
We use islets from NOD and db/db mice at different stages of diabetes development, EndoC-H1, WT mouse islets and MIN6 cells treated with cytokines or palmitate in vitro. m6A levels are analyzed with m6A RNA methylation Quantification kit, and their regulators with RT-qPCR and immunocytochemistry. Proliferation and survival are assessed with Click-It proliferation and CCK-8 viability assays.
Preliminary data detected first changes in expression of beta-cell markers in db/db mice as early as 4 weeks of age while ad libitum blood glucose levels are still normal. The first signs of increased UPR and inflammation were also seen. However, no differences in m6A regulators levels were observed. Further analysis of islets from older db/db and NOD mice are in progress. Pharmacological METTL3/14 inhibitors dose-dependently reduced the viability of EndoC-H1 and mouse MIN6 cells. The protective role of METTL3/14 activators are under investigation.
Current project is at the beginning of unveiling m6A role in diabetes and exploring its potential as therapeutic target.

Original language	English
Publication status	Published - 2025
MoE publication type	Not Eligible

Cite this

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title = "Novel METTL3/14 methyltransferase activators for protecting pancreatic beta cells in diabetes mellitus",

abstract = "RNA methylation of N6-adenosine (m6A) is a common reversible RNA modification, involved in various biological processes, e.g. RNA stability, splicing, translation. Recent research show that dysregulated m6A mRNA levels in islets is associated with diabetes, suggesting increasing m6A mRNA levels as a valuable target for beta-cell protection. The aim of this project is to elucidate a) mRNA m6A and their regulating proteins levels in healthy beta-cells and diabetes pathology, and b) the effect of METTL3/14 activator compounds on the proliferation and survival of cytokine- or palmitate treated beta-cells in vitro. We use islets from NOD and db/db mice at different stages of diabetes development, EndoC-H1, WT mouse islets and MIN6 cells treated with cytokines or palmitate in vitro. m6A levels are analyzed with m6A RNA methylation Quantification kit, and their regulators with RT-qPCR and immunocytochemistry. Proliferation and survival are assessed with Click-It proliferation and CCK-8 viability assays. Preliminary data detected first changes in expression of beta-cell markers in db/db mice as early as 4 weeks of age while ad libitum blood glucose levels are still normal. The first signs of increased UPR and inflammation were also seen. However, no differences in m6A regulators levels were observed. Further analysis of islets from older db/db and NOD mice are in progress. Pharmacological METTL3/14 inhibitors dose-dependently reduced the viability of EndoC-H1 and mouse MIN6 cells. The protective role of METTL3/14 activators are under investigation. Current project is at the beginning of unveiling m6A role in diabetes and exploring its potential as therapeutic target. ",

author = "Julia Konovalova and Huini Li and Maria Lindahl",

year = "2025",

language = "English",

}

TY - CONF

T1 - Novel METTL3/14 methyltransferase activators for protecting pancreatic beta cells in diabetes mellitus

AU - Konovalova, Julia

AU - Li, Huini

AU - Lindahl, Maria

PY - 2025

Y1 - 2025

N2 - RNA methylation of N6-adenosine (m6A) is a common reversible RNA modification, involved in various biological processes, e.g. RNA stability, splicing, translation. Recent research show that dysregulated m6A mRNA levels in islets is associated with diabetes, suggesting increasing m6A mRNA levels as a valuable target for beta-cell protection. The aim of this project is to elucidate a) mRNA m6A and their regulating proteins levels in healthy beta-cells and diabetes pathology, and b) the effect of METTL3/14 activator compounds on the proliferation and survival of cytokine- or palmitate treated beta-cells in vitro. We use islets from NOD and db/db mice at different stages of diabetes development, EndoC-H1, WT mouse islets and MIN6 cells treated with cytokines or palmitate in vitro. m6A levels are analyzed with m6A RNA methylation Quantification kit, and their regulators with RT-qPCR and immunocytochemistry. Proliferation and survival are assessed with Click-It proliferation and CCK-8 viability assays. Preliminary data detected first changes in expression of beta-cell markers in db/db mice as early as 4 weeks of age while ad libitum blood glucose levels are still normal. The first signs of increased UPR and inflammation were also seen. However, no differences in m6A regulators levels were observed. Further analysis of islets from older db/db and NOD mice are in progress. Pharmacological METTL3/14 inhibitors dose-dependently reduced the viability of EndoC-H1 and mouse MIN6 cells. The protective role of METTL3/14 activators are under investigation. Current project is at the beginning of unveiling m6A role in diabetes and exploring its potential as therapeutic target.

AB - RNA methylation of N6-adenosine (m6A) is a common reversible RNA modification, involved in various biological processes, e.g. RNA stability, splicing, translation. Recent research show that dysregulated m6A mRNA levels in islets is associated with diabetes, suggesting increasing m6A mRNA levels as a valuable target for beta-cell protection. The aim of this project is to elucidate a) mRNA m6A and their regulating proteins levels in healthy beta-cells and diabetes pathology, and b) the effect of METTL3/14 activator compounds on the proliferation and survival of cytokine- or palmitate treated beta-cells in vitro. We use islets from NOD and db/db mice at different stages of diabetes development, EndoC-H1, WT mouse islets and MIN6 cells treated with cytokines or palmitate in vitro. m6A levels are analyzed with m6A RNA methylation Quantification kit, and their regulators with RT-qPCR and immunocytochemistry. Proliferation and survival are assessed with Click-It proliferation and CCK-8 viability assays. Preliminary data detected first changes in expression of beta-cell markers in db/db mice as early as 4 weeks of age while ad libitum blood glucose levels are still normal. The first signs of increased UPR and inflammation were also seen. However, no differences in m6A regulators levels were observed. Further analysis of islets from older db/db and NOD mice are in progress. Pharmacological METTL3/14 inhibitors dose-dependently reduced the viability of EndoC-H1 and mouse MIN6 cells. The protective role of METTL3/14 activators are under investigation. Current project is at the beginning of unveiling m6A role in diabetes and exploring its potential as therapeutic target.

M3 - Poster

ER -