Author/Editor		Dolinar, Klemen; Chibalin, Alexander V.; Pirkmajer, Sergej
Title		ATIC as a link between antirheumatic drugs and regulation of energy metabolism in skeletal muscle
Type		članek
Vol. and No.		Letnik 121/122, št. 3/4
Publication year		2020
Volume		str. 129-145
ISSN		0031-5362 - Periodicum biologorum : an interdisciplinary international journal of the Societas Scientarium Naturalium Croatica established 1885
Language		eng
Abstract		hronic inflammatory rheumatic diseases, such as rheumatoid arthritis, psoriatic arthritis, and systemic lupus erythematosus, increase the risk of developing insulin resistance, metabolic syndrome, and/or type 2 diabetes. While inflammation is thought to be a major mechanism underlying meta-bolic dysregulation in rheumatic diseases, antirheumatic drugs that exert direct metabolic effects in addition to suppressing inflammation, might be particularly useful to prevent metabolic complications. Here we review an-tirheumatic drugs, such as methotrexate, that inhibit ATIC, the final en-zyme in the de novopurine biosynthesis, responsible for conversion of ZMP to IMP. Inhibition of ATIC results in accumulation of ZMP, thus promot-ing activation of AMP-activated protein kinase (AMPK), a major regulator of cellular energy metabolism and one of the most promising targets for the treatment of insulin resistance and type 2 diabetes. We focus especially on ATIC inhibition and AMPK activation in skeletal muscle as this is the largest and one of the most metabolically active tissues with a major role in glucose ho-meostasis. As an important site of insulin resistance, skeletal muscle is also one of the main target tissues for pharmacological therapy of type 2 diabetes. Finally, we review the metabolic effects of ATIC-inhibiting antirheumatic drugs and discuss whether these drugs might improve systemic glucose homeo-stasis by inhibiting ATIC and activating AMPK in skeletal muscle.
Keywords		rheumatic diseases diabetes skeletal muscle revmatske bolezni diabetes skeletna mišica