Berberine improves intralipid-induced insulin resistance in murine.

Autor: Dong ZH; Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Ji-nan, 250021, China.; Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Shandong Academy of Clinical Medicine, Ji-nan, 250021, China.; Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Ji-nan, 250021, China.; Cheeloo College of Medicine, Shandong University, Ji-nan, 250000, China.; Department of Endocrinology, Ji-nan Central Hospital, Cheeloo College of Medicine, Shandong University, Ji-nan, 250000, China., Lin HY; Department of Health Management Center, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Ji-nan, 250000, China., Chen FL; Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Ji-nan, 250021, China.; Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Shandong Academy of Clinical Medicine, Ji-nan, 250021, China.; Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Ji-nan, 250021, China., Che XQ; Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Ji-nan, 250021, China.; Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Shandong Academy of Clinical Medicine, Ji-nan, 250021, China.; Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Ji-nan, 250021, China.; Cheeloo College of Medicine, Shandong University, Ji-nan, 250000, China., Bi WK; Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Ji-nan, 250021, China.; Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Shandong Academy of Clinical Medicine, Ji-nan, 250021, China.; Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Ji-nan, 250021, China.; Cheeloo College of Medicine, Shandong University, Ji-nan, 250000, China., Shi SL; Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Ji-nan, 250021, China.; Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Shandong Academy of Clinical Medicine, Ji-nan, 250021, China.; Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Ji-nan, 250021, China., Wang J; Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Ji-nan, 250021, China.; Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Shandong Academy of Clinical Medicine, Ji-nan, 250021, China.; Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Ji-nan, 250021, China.; Cheeloo College of Medicine, Shandong University, Ji-nan, 250000, China., Gao L; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University and Shandong Academy of Medical Sciences, Ji-nan, 250000, China. linggao@sdu.edu.cn., He Z; Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Ji-nan, 250021, China. zhaohe7711@qq.com.; Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Shandong Academy of Clinical Medicine, Ji-nan, 250021, China. zhaohe7711@qq.com.; Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Ji-nan, 250021, China. zhaohe7711@qq.com.; Cheeloo College of Medicine, Shandong University, Ji-nan, 250000, China. zhaohe7711@qq.com., Zhao JJ; Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Ji-nan, 250021, China. jjzhao@sdu.edu.cn.; Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Shandong Academy of Clinical Medicine, Ji-nan, 250021, China. jjzhao@sdu.edu.cn.; Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Ji-nan, 250021, China. jjzhao@sdu.edu.cn.
Jazyk: angličtina
Zdroj: Acta pharmacologica Sinica [Acta Pharmacol Sin] 2021 May; Vol. 42 (5), pp. 735-743. Date of Electronic Publication: 2020 Aug 07.
DOI: 10.1038/s41401-020-0493-4
Abstrakt: 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.
Databáze: MEDLINE
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