Berberine improves intralipid-induced insulin resistance in murine  

作　　者：Zhen-hua Dong Hai-yan Lin Fu-lian Chen Xiao-qi Che Wen-kai Bi Shu-long Shi Jing Wang Ling Gao Zhao He Jia-jun Zhao 

机构地区：[1]Department of Endocrinology,Shandong Provincial Hospital,Cheeloo College of Medicine,Shandong University,Ji-nan,250021,China [2]Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism,Shandong Academy of Clinical Medicine,Ji-nan,250021,China [3]Institute of Endocrinology and Metabolism,Shandong Academy of Clinical Medicine,Ji-nan,250021,China [4]Cheeloo College of Medicine,Shandong University,Ji-nan,250000,China [5]Department of Endocrinology,Ji-nan Central Hospital,Cheeloo College of Medicine,Shandong University,Ji-nan,250000,China [6]Department of Health Management Center,Shandong Provincial Hospital,Cheeloo College of Medicine,Shandong University,Ji-nan,250000,China [7]Department of Endocrinology,Shandong Provincial Hospital Affiliated to Shandong First Medical University and Shandong Academy of Medical Sciences,Ji-nan,250000,China

出　　处：《Acta Pharmacologica Sinica》2021年第5期735-743,共9页中国药理学报（英文版）

基　　金：This work was supported by the National Key Research and Development Program of China(grant number:2017YFC1309800);National Natural Science Foundation of China(grant number:81400788);Medical and Health Technology Development Project of Shandong province(grant number:2019WS076);Scientific Research Project of Ji-nan(201909039);Scientific Research Project of Weifang Health Committee(wfwsjk_2019_121).

摘　　要：Insulin resistance (IR) is a major metabolic risk factor even before the onset of hyperglycemia. Recently, berberine (BBR) is found to improve hyperglycemia and IR. In this study, we investigated whether BBR could improve IR independent of hyperglycemia. Acute insulin-resistant state was induced in rats by systemic infusion of intralipid (6.6%). BBR was administered via different delivery routes before or after the beginning of a 2-h euglycemic-hyperinsulinemic clamp. At the end of experiment, rats were sacrificed, gastrocnemius muscle was collected for detecting mitochondrial swelling, phosphorylation of Akt and AMPK, as well as the mitochondrial permeability regulator cyclophilin D (CypD) protein expression. We showed that BBR administration markedly ameliorated intralipid-induced IR without affecting blood glucose, which was accompanied by alleviated mitochondrial swelling in skeletal muscle. We used human skeletal muscle cells (HSMCs), AML12 hepatocytes, human umbilical vein endothelial cells, and CypD knockout mice to investigate metabolic and molecular alternations. In either HSMCs or AML12 hepatocytes, BBR (5 μM) abolished palmitate acid (PA)-induced increase of CypD protein levels. In CypD-deficient mice, intralipid-induced IR was greatly attenuated and the beneficial effect of BBR was diminished. Furthermore, we demonstrated that the inhibitory effect of BBR on intralipid-induced IR was mainly mediated by skeletal muscle, but not by intestine, liver, or microvasculature;BBR administration suppressed intralipid-induced upregulation of CypD expression in skeletal muscle. These results suggest that BBR alleviates intralipid-induced IR, which is related to the inhibition of CypD protein expression in skeletal muscle.

关 键 词：BERBERINE INTRALIPID insulin resistance skeletal muscle mitochondrial swelling cyclophilin D euglycemic-hyperinsulinemic clamp 

分 类 号：R96[医药卫生—药理学]