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匹伐他汀与L-谷氨酰胺的新用途:在高脂血症2型糖尿病小鼠模型中补充β细胞

Repurposing Pitavastatin and L-Glutamine: Replenishing β-Cells in Hyperlipidemic Type 2 Diabetes Mouse Model.

作者信息

Palit Sayantani Pramanik, Patel Roma, Parmar Nishant, Rathwa Nirali, Dalvi Nilay, Ramachandran A V, Begum Rasheedunnisa

机构信息

Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara 390002, Gujarat, India.

School of Liberal Studies and Education, Navrachana University, Vadodara 391410, Gujarat, India.

出版信息

Life (Basel). 2023 Apr 1;13(4):929. doi: 10.3390/life13040929.

DOI:10.3390/life13040929
PMID:37109458
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10143944/
Abstract

Type 2 diabetes (T2D) is associated with obesity and declining β-cells. L-glutamine has been implicated in the amelioration of T2D by virtue of its incretin secretagogue property while, there are mixed reports on pitavastatin's adiponectin potentiating ability. We aimed to investigate the effect of pitavastatin (P), L-glutamine (LG), and combination (P + LG) on glycemic control and β-cell regeneration in a high-fat diet (HFD) + streptozotocin (STZ)-induced T2D mouse model. C57BL6/J mice treated with HFD + STZ were divided into four groups: diabetes control (HFD + STZ), P, LG, and P + LG, while the control group (NCD) was fed with the normal-chow diet. Significant amelioration was observed in the combination therapy as compared to monotherapies in respect of (i) insulin resistance, glucose intolerance, lipid profile, adiponectin levels, and mitochondrial complexes I, II, and III activities, (ii) reduced phosphoenolpyruvate carboxykinase, glucose 6-phophatase, glycogen phosphorylase, and GLUT2 transcript levels with increased glycogen content in the liver, (iii) restoration of insulin receptor 1β, pAkt/Akt, and AdipoR1 protein levels in skeletal muscle, and (iv) significant increase in islet number due to β-cell regeneration and reduced β-cell death. L-glutamine and pitavastatin in combination can ameliorate T2D by inducing β-cell regeneration and regulating glucose homeostasis.

摘要

2型糖尿病(T2D)与肥胖及β细胞功能衰退相关。L-谷氨酰胺因其肠促胰岛素分泌特性而被认为对改善T2D有作用,而关于匹伐他汀增强脂联素的能力则有不同的报道。我们旨在研究匹伐他汀(P)、L-谷氨酰胺(LG)及其组合(P+LG)对高脂饮食(HFD)+链脲佐菌素(STZ)诱导的T2D小鼠模型血糖控制及β细胞再生的影响。用HFD+STZ处理的C57BL6/J小鼠分为四组:糖尿病对照组(HFD+STZ)、P组、LG组和P+LG组,而对照组(NCD)给予正常饲料饮食。与单一疗法相比,联合疗法在以下方面观察到显著改善:(i)胰岛素抵抗、葡萄糖耐量、血脂谱、脂联素水平以及线粒体复合物I、II和III的活性;(ii)肝脏中磷酸烯醇式丙酮酸羧激酶、葡萄糖6-磷酸酶、糖原磷酸化酶和GLUT2转录水平降低,糖原含量增加;(iii)骨骼肌中胰岛素受体1β、pAkt/Akt和AdipoR1蛋白水平恢复;(iv)由于β细胞再生导致胰岛数量显著增加,β细胞死亡减少。L-谷氨酰胺和匹伐他汀联合使用可通过诱导β细胞再生和调节葡萄糖稳态来改善T2D。

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A genetic analysis identifies a haplotype at adiponectin locus: Association with obesity and type 2 diabetes.一项遗传分析确定了脂联素基因座的单倍型:与肥胖和 2 型糖尿病的关联。
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