Publication date: 5 July 2017
Source:Cell Metabolism, Volume 26, Issue 1
Author(s): Elif A. Oral, Shannon M. Reilly, Andrew V. Gomez, Rasimcan Meral, Laura Butz, Nevin Ajluni, Thomas L. Chenevert, Evgenia Korytnaya, Adam H. Neidert, Rita Hench, Diana Rus, Jeffrey F. Horowitz, BreAnne Poirier, Peng Zhao, Kim Lehmann, Mohit Jain, Ruth Yu, Christopher Liddle, Maryam Ahmadian, Michael Downes, Ronald M. Evans, Alan R. Saltiel
Numerous studies indicate an inflammatory link between obesity and type 2 diabetes. The inflammatory kinases IKKɛ and TBK1 are elevated in obesity; their inhibition in obese mice reduces weight, insulin resistance, fatty liver and inflammation. Here we studied amlexanox, an inhibitor of IKKɛ and TBK1, in a proof-of-concept randomized, double-blind, placebo-controlled study of 42 obese patients with type 2 diabetes and nonalcoholic fatty liver disease. Treatment of patients with amlexanox produced a statistically significant reduction in Hemoglobin A1c and fructosamine. Interestingly, a subset of drug responders also exhibited improvements in insulin sensitivity and hepatic steatosis. This subgroup was characterized by a distinct inflammatory gene expression signature from biopsied subcutaneous fat at baseline. They also exhibited a unique pattern of gene expression changes in response to amlexanox, consistent with increased energy expenditure. Together, these data suggest that dual-specificity inhibitors of IKKɛ and TBK1 may be effective therapies for metabolic disease in an identifiable subset of patients.
Graphical abstract
Teaser
Oral et al. investigate the effect of the anti-inflammatory, antiallergic drug amlexanox in a proof-of-concept clinical study of type 2 diabetes and nonalcoholic fatty liver disease. Amlexanox improved blood glucose levels in diabetic patients, and a subgroup showed enhanced response, including liver fat loss, associated with increased energy expenditure.http://ift.tt/2sRs8Yv
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου