首页|STING signaling in islet macrophages impairs insulin secretion in obesity

STING signaling in islet macrophages impairs insulin secretion in obesity

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The innate immune regulator stimulator of interferon genes(STING)mediates self-DNA sensing and leads to the induction of type Ⅰinterferons and inflammatory cytokines,which promotes the progression of various inflammatory and autoimmune diseases.Innate im-mune system plays a critical role in regulating obesity-induced islet dysfunction,whereas the potential effect of STING signaling is not fully understood.Here,we demonstrate that STING is mainly expressed and activated in islet macrophages upon high-fat diet(HFD)feeding.Sting-/-alleviates HFD-induced islet inflammation by inhibiting the expression of pro-inflammatory cytokines and the infiltration of macrophages.Mechanically,palmitic acid incubation promotes mitochondrial DNA leakage into the cytosol and subsequently activates STING pathway in macrophages.Additionally,STING activation in macrophages impairs glucose-stimulated insulin secretion by mediating the engulfment of β cell insulin secretory granules.Pharmacologically inhibiting STING activation enhances insulin secretion to control hyperglycemia.Together,our results reveal a regulatory mechanism in controlling the islet inflammation and insulin secretion in diet-induced obesity and suggest that selective blocking of the STING activation may be a promising strategy for treating type 2 diabetes.

STINGobesitytype 2 diabetesinsulinmacrophagesislet

Ze Hong、Saihua Chen、Jing Sun、Dan Cheng、Hanli Guo、Jiahao Mei、Xiang Zhang、Munire Maimaiti、Haiping Hao、Peng Cao、Haiyang Hu、Chen Wang

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School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210023,China

State Key Laboratory of Natural Medicines,Department of Life Science and Technology,China Pharmaceutical University,Nanjing 211198,China

School of Life Sciences,Westlake University,Hangzhou 310012,China

National Key Research and Development Program of ChinaNational Key Research and Development Program of ChinaChina Postdoctoral Research Programthe"Double First-Class"Project of China Pharmaceutical UniversityNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNatural Science Foundation of ChongqingKey R&D Project of Jiangsu Province

2022YFC23032002021YFF07020032019TQ0356CPU2022QZ01317300188217175182204408CSTB2022NSCQ-MSX1114BE2020725

2024

10.1007/s11427-022-2371-9

中国科学:生命科学(英文版)
中国科学院

中国科学:生命科学(英文版)

CSTPCD
影响因子：0.806
ISSN：1674-7305
年,卷(期)：2024.67(2)
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