Finding The Cause Of Muscle Loss In Diabetes

Using mouse models of diabetes, scientists have identified the proteins WWP1 and KLF15 as key players in muscle loss under diabetic conditions.

AsianScientist (Mar. 11, 2019) – Researchers in Japan have identified two proteins in diabetic patients responsible for muscle atrophy. They published their findings in the journal JCI Insight.

Diabetes mellitus is a disease caused by the insufficient action of the hormone insulin. Insulin not only lowers blood sugar levels but also promotes the growth and proliferation of cells. Hence, without insulin activity, the growth and proliferation of muscle cells is suppressed, which in turn contributes to the decline in skeletal muscle mass.

In the present study, researchers led by Professor Wataru Ogawa at the Kobe University Graduate School of Medicine, Japan, revealed that high blood sugar levels resulted in an increase in the expression of two proteins, WWP1 and KLF15, leading to muscle atrophy under diabetic conditions.

The team observed increased levels of KLF15 in the skeletal muscle of diabetic mice, which corresponded to the loss of skeletal muscle mass. Meanwhile, mice that lacked KLF15 specifically in their muscles were resistant to diabetes-induced skeletal muscle mass decline. These results indicate that diabetes-induced muscle loss is attributable to increased amounts of KLF15.

The team further demonstrated that when blood sugar levels rise, the amount of WWP1 decreases, which in turn slows down the degradation of KLF15. The accumulation of KFL15 in skeletal muscle cells eventually causes muscle loss.

“If we develop a drug that strengthens the function of WWP1 or weakens the function of KLF15, it would lead to a groundbreaking new treatment,” said Ogawa.

The article can be found at: Hirata et al. (2019) Hyperglycemia Induces Skeletal Muscle Atrophy via a WWP1/KLF15 Axis.


Source: Kobe University; Photo: Shutterstock.
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