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Glucose and brown fat

Glucose uptake in brown fat could treat T2DM

Brown fat
The signal pathway in brown fat can most likely be activated even in patients with type 2 diabetes, where the insulin signalling is impaired

Researchers at Stockholm University have discovered a mechanism that stimulates glucose uptake in brown fat, a tissue whose primary function is to generate heat by burning fat and sugar. It is hoped that the findings, published in the Journal of Cell Biology, can be used to develop a new type of medicine for type 2 diabetes. The major breakthrough of this discovery is of how glucose uptake is stimulated in brown fat and could be used to pharmacologically stimulate this signalling pathway and lower blood sugar levels.

“One of the most interesting characteristics of this newly discovered signal pathway is that it differs from the signal pathway triggered by insulin,” said Professor Tore Bengtsson from the Department of Molecular Biosciences, the Wenner-Gren Institute, Stockholm University. “This means that the signal pathway in brown fat can most likely be activated even in patients with type 2 diabetes, where the insulin signalling is impaired.”

Professor Tore Bengtsson

Brown fat has been shown to be active in adults and is one of the tissues in the body that can be stimulated to the highest uptake of glucose per gram of tissue. Consequently, an increase in the uptake of glucose in brown fat can rapidly lower blood sugar levels.

IN this study, the researchers demonstrated that mechanistic target of rapamycin (mTOR) complex 2 has a novel role in β3-adrenoceptor–stimulated glucose uptake in brown adipose tissue. They showed that β3-adrenoceptors stimulate glucose uptake in brown adipose tissue via a signalling pathway that is comprised of two different parts: one part dependent on cAMP-mediated increases in GLUT1 transcription and de novo synthesis of GLUT1 and another part dependent on mTOR complex 2–stimulated translocation of newly synthesised GLUT1 to the plasma membrane, leading to increased glucose uptake.

They noted that both parts are essential for β3-adrenoceptor–stimulated glucose uptake. Importantly, the effect of β3-adrenoceptor on mTOR complex 2 is independent of the classical insulin–phosphoinositide 3-kinase–Akt pathway, highlighting a novel mechanism of mTOR complex 2 activation.

“Our study shows that the body’s own stress hormones, epinephrine and norepinephrine, increase the uptake of glucose in brown fat,” he added. “Epinephrine and norepinephrine can affect almost all our bodily organs by binding to receptors on the surface of a cell. We have shown how, and by what mechanism, adrenergic receptors found on brown fat stimulate the uptake of glucose. This is completely new and ground-breaking research. Finding new ways to stimulate glucose uptake in tissues and thereby lower blood sugar levels is thus a matter of great interest.”

The study was partly funded by the Swedish Research Council and carried out by researchers from Stockholm University.

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