Insulin production: New insights into its biology

A new role for N6-Adenosine methylation in insulin production.

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Understanding the intricate biology of insulin production is vital in unraveling the complexities of metabolic regulation and its implications for various health conditions. This study delves into the mechanisms and processes involved in insulin synthesis, secretion, and regulation of glucose metabolism. By shedding light on the fundamental aspects of insulin production, we aim to contribute valuable insights that could pave the way for improved therapeutic approaches for diabetes and related disorders.

Researchers at the University of Michigan have made a significant discovery regarding the first step of insulin synthesis. Investigating messenger RNAs involved in insulin production in fruit flies, they found that a chemical tag on the mRNA plays a crucial role in translating the insulin mRNA into the protein insulin. Altering this chemical tag can impact the amount of insulin produced.

The study, led by Daniel Wilinski and Monica Dus, sheds light on the importance of these chemical tags in regulating insulin production and is published in the journal Nature Structural and Molecular Biology. Understanding this process could lead to new insights into diabetes treatment and management.

Wilinski, a postdoctoral researcher in Dus’ lab in the U-M Department of Molecular, Cellular, and Developmental Biology, said, “I like to think of RNA as a Christmas tree. Christmas trees are beautiful in the wilderness, but when you bring them inside and put ornaments on them, that decoration makes you feel like the tree is part of the season. Same thing with RNA. These decorations on RNA enhance the way RNA is regulated.”

Studying insulin production in humans or mammals presents challenges due to the limited accessibility and regenerative capabilities of the pancreas. However, fruit flies offer a unique advantage as their insulin cells reside in their brains, making them physically accessible to researchers. In this study, researchers focused on a chemical tag called RNA N-6 adenosine methylation (m6A) and its impact on insulin production.

Using advanced techniques like confocal microscopy and CRISPR gene editing, they discovered that the presence of the m6A tag significantly increased insulin production in fruit flies. Conversely, insulin production drastically decreased when the tag was removed, leading to diabetes-like characteristics. This novel insight sheds light on the intricate mechanisms of insulin synthesis. It has the potential to enhance our understanding of diabetes and its treatment.

Studying insulin production in humans or mammals presents challenges due to the limited accessibility and regenerative capabilities of the pancreas. However, fruit flies offer a unique advantage as their insulin cells reside in their brains, making them physically accessible to researchers. In this study, researchers focused on a chemical tag called RNA N-6 adenosine methylation (m6A) and its impact on insulin production.

Using advanced techniques like confocal microscopy and CRISPR gene editing, they discovered that the presence of the m6A tag significantly increased insulin production in fruit flies. Conversely, insulin production drastically decreased when the tag was removed, leading to diabetes-like characteristics. This novel insight sheds light on the intricate mechanisms of insulin synthesis. It has the potential to enhance our understanding of diabetes and its treatment.

The conserved chemical tag, RNA N-6 adenosine methylation (m6A), found in fish, mice, and humans, suggests that insulin production may also be regulated similarly in humans. With the global obesity and diabetes epidemic, this discovery adds to understanding insulin biology and energy homeostasis-related diseases.

Low levels of these chemical tags have been observed in individuals with Type 2 diabetes, indicating a potential link. Restoring the stories of these tags could be a promising approach to combat diabetes and metabolic diseases. Despite a century of knowledge about insulin as a treatment, this research highlights the importance of delving into the fundamental molecular biology of insulin and its regulation, emphasizing the need for further discoveries in this area.

Journal Reference:

  1. Wilinski, D., Dus, M., et al., N6-adenosine methylation controls the translation of insulin mRNA. Natural Structural Molecular Biology. DOI:10.1038/s41594-023-01048-x.