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Jeremy Faust, an emergency medicine physician and public health expert at Brigham and Womens Hospital who was not involved in the study, called the results amazing. We already know that these drugs are going to make a huge difference for obesity and metabolic syndromes that cause cardiovascular disease and other organ damage, said Faust, who wrote an editorial to accompany the results
Glucagon receptor activation increases energy expenditure through thermogenesis, enhances fat oxidation and breakdown, improves overall metabolic rate, and provides additional appetite regulation through central nervous system effects
TM2, in particular, adopts a conformation in the orforglipron-bound structure that would be difficult to predict computationally, highlighting the receptor's conformational flexibility and the inherent limitations of structure-based drug design for class B GPCRs
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