Slowing Diabetes Progression with Mitochondrial Peptide MOTS-c > GENERAL HOSPITAL

Is diabetes simply a disease of elevated blood sugar? In fact, the important process of 'cellular senescence' is hidden behind it.

When pancreatic beta cells, which secrete insulin, age and their function declines,

the ability to regulate blood sugar gradually weakens, eventually leading to diabetes.

A research team led by Professor Cho Young-min at Seoul National University Hospital has proposed a new strategy to slow the progression of diabetes by directly targeting cellular senescence.

The researchers demonstrated that the mitochondrial-derived peptide MOTS-c inhibits the senescence of pancreatic beta cells and restores their function,

improving blood sugar control in both type 1 and type 2 diabetes models.

This research is significant because it presents a new treatment paradigm that targets cellular senescence itself, unlike existing 'blood sugar-lowering drugs'.

Mitochondrial Peptide MOTS-c Slows Diabetes Progression

- Confirmed the effect of inhibiting pancreatic beta cell senescence in human islet cells and type 1 and type 2 diabetic animal models

- MOTS-c → Regulation of metabolic pathways → Inhibition of pancreatic beta cell senescence → Preservation of insulin function → Delay in diabetes progression

Seoul National University Hospital research team has proposed a new strategy to slow the progression of diabetes by directly targeting cellular senescence. The mitochondrial-derived peptide 'MOTS-c' inhibits the senescence of pancreatic beta cells and protects their function, demonstrating improved blood sugar control in human islet cells* and type 1 and type 2 diabetes models. This achievement shows the potential to expand the paradigm of diabetes treatment.

*Human islet cells: A collection of cells, including beta cells, that secrete insulin in the pancreas

The core cause of diabetes is the decline and loss of function of pancreatic beta cells, which synthesize and secrete insulin. In particular, as beta cells undergo cellular senescence with age, their ability to secrete insulin decreases, and this process plays an important role in the development and progression of diabetes. However, until now, there have been few treatment strategies that directly control cellular senescence.

Professor Cho Young-min's team (first author Dr. Gong Byeong-soo) at the Department of Endocrinology and Metabolism, Seoul National University Hospital, focused on the potential of the peptide MOTS-c, which is expressed from mitochondrial DNA. MOTS-c was first discovered in 2007 in a joint study between Seoul National University Hospital and the Tokyo Metropolitan Institute of Gerontology in Japan and originated from regions related to lifespan and diabetes risk regulation. Although its function in regulating glucose metabolism has been known, its association with pancreatic beta cell senescence and diabetes progression has not been confirmed.

The research team examined the expression and action of MOTS-c in human islet cells, aged mice, and type 1 and type 2 diabetes model mice. As a result, MOTS-c levels were significantly reduced in islet cells that were aged or had diabetes. When the research team administered MOTS-c to islet cells of aged mice, cellular senescence markers (p16, γ-H2AX, etc.) decreased, and the insulin secretion function of pancreatic beta cells was restored.

In addition, in the S961-induced mouse model of type 2 diabetes (an animal model in which diabetes is induced by administering an insulin receptor antagonist), the incidence of diabetes in the control group increased to approximately 70% within 2 weeks, but in the MOTS-c-treated group, it was only about 30%, significantly delaying the onset. The same effect of suppressing blood sugar increases and delaying onset was also confirmed in the NOD mouse, a type 1 diabetes model (an animal model in which diabetes occurs due to an autoimmune response). In other words, MOTS-c commonly protects pancreatic beta cells in diabetes caused by different factors such as aging, insulin resistance, and autoimmune responses.

Through additional mechanism research, the research team revealed that MOTS-c regulates the mTOR signaling pathway and the aspartate-glutamate metabolic pathway in islet cells. The two pathways play an important role in cell growth and metabolism, but abnormalities can promote cellular senescence. MOTS-c normalizes these pathways to inhibit cellular senescence and maintain function, showing that it can be a new treatment strategy that targets pancreatic beta cell senescence itself, unlike existing treatments that simply lower blood sugar.

Professor Cho Young-min (Department of Endocrinology and Metabolism) explained, "This study reaffirms that islet cell senescence is an important pathological mechanism of diabetes and shows that the mitochondrial-derived peptide MOTS-c can be a candidate for anti-aging therapy. If MOTS-c research is expanded in the future, it could open up new possibilities for managing not only geriatric diabetes but also various metabolic diseases."

This research result was published in the latest issue of the international journal 'Experimental & Molecular Medicine (IF 12.9)'.

[Photo] Professor Cho Young-min, Department of Endocrinology and Metabolism, Seoul National University Hospital

Source :https://blog.naver.com/chsnuh/224000074394

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