Berberine alleviates the cerebrovascular contractility in streptozotocin-induced diabetic rats through modulation of intracellular Ca2 handling in smooth muscle cellsReport as inadecuate




Berberine alleviates the cerebrovascular contractility in streptozotocin-induced diabetic rats through modulation of intracellular Ca2 handling in smooth muscle cells - Download this document for free, or read online. Document in PDF available to download.

Cardiovascular Diabetology

, 15:63

First Online: 12 April 2016Received: 12 January 2016Accepted: 01 April 2016

Abstract

BackgroundVascular dysfunction is a distinctive phenotype in diabetes mellitus. Current treatments mostly focus on the tight glycemic control and few of these treatments have been designed to directly recover the vascular dysfunction in diabetes. As a classical natural medicine, berberine has been explored as a possible therapy for DM. In addition, it is reported that berberine has an extra-protective effect in diabetic vascular dysfunction. However, little is known whether the berberine treatment could ameliorate the smooth muscle contractility independent of a functional endothelium under hyperglycemia. Furthermore, it remains unknown whether berberine affects the arterial contractility by regulating the intracellular Ca handling in vascular smooth cells VSMCs under hyperglycemia.

MethodsSprague–Dawley rats were used to establish the diabetic model with a high-fat diet plus injections of streptozotocin STZ. Berberine 50, 100, and 200 mg-kg-day were intragastrically administered to control and diabetic rats for 8 weeks since the injection of STZ. The intracellular Ca handling of isolated cerebral VSMCs was investigated by recording the whole-cell L-type Ca channel CaL currents, assessing the protein expressions of CaL channel, and measuring the intracellular Ca in response to caffeine. Our results showed that chronic administration of 100 mg-kg-day berberine not only reduced glucose levels, but also inhibited the augmented contractile function of cerebral artery to KCl and 5-hydroxytryptamine 5-HT in diabetic rats. Furthermore, chronic administration of 100 mg-kg-day berberine significantly inhibited the CaL channel current densities, reduced the α1C-subunit expressions of CaL channel, decreased the resting intracellular Ca Cai level, and suppressed the Ca releases from RyRs in cerebral VSMCs isolated from diabetic rats. Correspondingly, acute application of 10 μM berberine could directly inhibit the hyperglycemia-induced CaL currents and suppress the hyperglycemia-induced Ca releases from RyRs in cerebral VSMCs isolated from normal control rats.

ConclusionsOur study indicated that berberine alleviated the cerebral arterial contractility in the rat model of streptozotocin-induced diabetes via regulating the intracellular Ca handling of smooth muscle cells.

KeywordsBerberine Contractile function Vascular smooth muscle cells VSMCs L-type Ca channel CaL Ca releases AbbreviationsDMdiabetes mellitus

Caiconcentration of intracellular Ca

VSMCsvascular smooth muscle cells

CaLlong-lasting voltage-dependent Ca L-type Ca channel

RyRsryanodine receptors

STZstreptozotocin

5-HT5-hydroxytryptamine

CICRCa-induced Ca release

KCaCa-activated K channel

AMPKadenosine monophosphate-activated protein kinase

eNOSendothelial nitric oxide synthase

AGEsadvanced glycation end products

Yu-Guang Ma and Yin-Bin Zhang contributed equally to this work

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Author: Yu-Guang Ma - Yin-Bin Zhang - Yun-Gang Bai - Zhi-Jun Dai - Liang Liang - Mei Liu - Man-Jiang Xie - Hai-Tao Guan

Source: https://link.springer.com/article/10.1186/s12933-016-0382-9







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