The study discovers molecular mechanisms behind insulin resistance in skeletal muscles

Insulin resistance precedes and predicts the beginning of type 2 diabetes (DM2), a chronic disease that causes high incidence and mortality around the world. In the affected people, insulin is not able to facilitate glucose capture by tissues and organs, which leads to an increase in blood glucose (chronic hyperglycemia). Because the skeletal muscle is a tissue that uses the most glucose in response to insulin, it is the most affected tissue by insulin resistance.

Now the study published in the description of new molecular mechanisms to understand insulin resistance in skeletal muscles and outline future drug goals for DM2.

The study is conducted by Manuel Vázquez-Carrer, with UB’s Faculty of Pharmacy and Food Sciences, Biomedicine of the UB Institute (IBUB) and Sant Joan de Déu Research Institute (IRSJD) and Biomedical Research Center Metabolic Disease (Ciberd). Ricardo Rodríguez-Calvo (Ciberd and Universitat Rovira and Virgili), Antoni Camins (Ubneuro and Ciberned) and Walter Whatea, with the University of Lusanne (Switzerland), also signed an article.

Insulin receptor’s role testing

Poorly controlled diabetes is a serious global health problem that can damage blood vessels, heart, eyes, eyes, kidneys and other organs. Studies have shown that when developing insulin resistance, many steps were changed in the metabolic trail activated by insulin. However, much less attention has been paid to what is happening to the insulin receptor so far.

Professor Manuel Vázquez-Carrer notes that “insulin signal trail is initiated when insulin is associated with the receptor on tissue cells reacting to insulin. This receptor consists of an insulin receptor α subunit (INSRα) and β subunits (INSRβ) “.

“Insulin binding from INSRα derepresses the activity of tyrosine kinase β (Insrβ) subunit. This initiates the entire metabolic trail with different stages, which ultimately allow glucose transporters from the interior to the cell membrane to enable glucose to enter glucose. ” continues.

The study assesses whether the receptor activated by the proliferator of peroxysomes (PPAR) β/δ may regulate the INSRβ levels in mouse muscles and miotubs in breeding.

The results show that the removal of the gene in mice reduces the levels of INSRβ protein in skeletal muscles compared to mice not genetically modified. GW501516 – agonist PPARβ/δ – It has also been shown that it increases the level of insrβ protein in mouse muscles. “

Professor Manuel Vázquez-Carrer

The expert adds that “reduction of INSRβ levels in bred brooms caused by the activator of endoplasmic reticulum stress – the process involved in the development of insulin and DM2 resistance – is partly reversed when the cells are incubated in the presence of this agonist PPARβ/Δ agonist.” The agonist also reduced reticulum stress and activity Lisosomal, of which the latter is responsible for degrading the INSRβ protein, which can explain the beneficial effect of this compound on the levels of this protein, “he says.

The results also reveal how the levels of tyrosine kinase protein Efryna B4 (EPHB4)-the factory is associated with the INSRβ and facilitates its endocytosis and degradation of lysosomes-developed in skeletal muscles from mouse with a deficiencies of PPARβ/δ. However, the agonist PPARβ/Δ reduced skeletal muscle levels from non -native modified mice.

The results of this study identify new mechanisms with which PPARβ/δ regulates INSRβ protein levels in skeletal muscles. “The study describes the new actions of this nuclear receptor that can help explain its beneficial effect on insulin and DM2 resistance,” sums up Vázquez-Carrer.