Obese individuals even with normal glucose tolerance(NGT)are at higher risk for developing type 2 diabetes(T2D),and obesity is associated with inflammation.However,mechanisms linking inflammation to beta-cell function...Obese individuals even with normal glucose tolerance(NGT)are at higher risk for developing type 2 diabetes(T2D),and obesity is associated with inflammation.However,mechanisms linking inflammation to beta-cell function and insulin sensitivity in NGT individuals are not fully understood.We aimed to investigate the relationships between inflammation-related proteins(IRPs)and insulin dynamics in NGT subjects.The explorations were conducted using data from 1109 non-diabetes subjects aged 40–44 with normal or excess body weight and 21 Chinese NGT subjects aged 22–32 with accurate metabolic assessment.IRPs were detected with Olink technology.Insulin sensitivity and beta-cell function were evaluated with hyperinsulinemic–euglycemic clamp and hyperglycemic clamp.Eight associators were identified with obesity in NGT subjects,among which MCP-3,IL-6,TWEAK,HGF,and CST5 also showed associations in non-diabetes people.Four IRPs were linked to insulin sensitivity,with IL-24 being a novel finding.Seven IRPs were related to beta-cell function,including novel associators CD244,CD40,and IL-15RA.Moreover,most IRPs were interconnected,with IL-6 as the hub.In conclusion,insulin sensitivity and beta-cell function are related to IRPs involved in chemotaxis,activation of immune cells,and cell proliferation,which might provide valuable information for the understanding of the mechanisms associated with T2D pathogenesis.展开更多
基金supported by grants from the National Key Research and Development Program of China(2022YFA1004804)Shanghai Municipal Key Clinical Specialty,Shanghai Research Center for Endocrine and MetabolicDiseases(2022ZZ01002)+6 种基金National Natural Science Foundation of China(NSFC)major international(regional)joint research project(81220108006)to W.J.the Excellent Young Scientists Fund of NSFC(82022012)General Fund of NSFC(82270907)Major Program of NSFC(92357305)Innovative Research Team of High-level Local Universities in Shanghai(SHSMU-ZDCX20212700)Hong Kong Scholars Program(XJ2013035)Two Hundred Program from Shanghai Jiao Tong University School of Medicine to H.L.
文摘Obese individuals even with normal glucose tolerance(NGT)are at higher risk for developing type 2 diabetes(T2D),and obesity is associated with inflammation.However,mechanisms linking inflammation to beta-cell function and insulin sensitivity in NGT individuals are not fully understood.We aimed to investigate the relationships between inflammation-related proteins(IRPs)and insulin dynamics in NGT subjects.The explorations were conducted using data from 1109 non-diabetes subjects aged 40–44 with normal or excess body weight and 21 Chinese NGT subjects aged 22–32 with accurate metabolic assessment.IRPs were detected with Olink technology.Insulin sensitivity and beta-cell function were evaluated with hyperinsulinemic–euglycemic clamp and hyperglycemic clamp.Eight associators were identified with obesity in NGT subjects,among which MCP-3,IL-6,TWEAK,HGF,and CST5 also showed associations in non-diabetes people.Four IRPs were linked to insulin sensitivity,with IL-24 being a novel finding.Seven IRPs were related to beta-cell function,including novel associators CD244,CD40,and IL-15RA.Moreover,most IRPs were interconnected,with IL-6 as the hub.In conclusion,insulin sensitivity and beta-cell function are related to IRPs involved in chemotaxis,activation of immune cells,and cell proliferation,which might provide valuable information for the understanding of the mechanisms associated with T2D pathogenesis.
