牛磺酸通过刺激 α 细胞转分化来缓解胰腺 β 细胞应激,Biofactors

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牛磺酸通过刺激 α 细胞转分化来缓解胰腺 β 细胞应激
Biofactors ( IF 5.0 ) Pub Date : 2023-01-30 , DOI: 10.1002/biof.1938
Dipak Sarnobat ₁ , R Charlotte Moffett ₁ , Jinfang Ma ₂ , Peter R Flatt ₁ , Neville H McClenaghan _{1,

3} , Andrei I Tarasov ₁

Affiliation

半必需氨基酸牛磺酸已被证明可以减轻人类的肥胖和高血糖症；然而，尚未确定抗糖尿病作用的潜在途径。我们探讨了慢性牛磺酸暴露对退行性 1 型糖尿病患者胰岛细胞生物学的影响。后者是通过在小鼠中注射小剂量链脲佐菌素 (STZ) 5 天，然后在饮用水中给予牛磺酸（2% w/v，口服）10 天来建模的。牛磺酸治疗对抗 STZ 糖尿病诱导的胰岛形态和 β-/α- 细胞比例的有害变化，巧合的是 β- 细胞的增殖显着增强 3.9 ± 0.7 倍，细胞凋亡减少 40 ± 5%。与这些发现一致，治疗抵消了抗氧化剂的上调（在胰腺 β 细胞系中，STZ 诱导的Sod1、Sod2、Cat、Gpx1）和胰岛扩张（Ngn3、Itgb1 ）基因的下调。同时，牛磺酸将 α 细胞向 β 细胞的转分化增强了 2.3 ± 0.8 倍，这与胰腺 α 细胞中细胞溶质 Ca ^{2+水平的强烈非代谢升高相呼应。}我们的数据表明膳食牛磺酸对胰岛 β 细胞生物学具有双峰效应，它结合了 α-/β- 细胞转分化的增强和细胞凋亡的下调。可能源于信号的细胞内和细胞外形态的作用二元论可能解释了牛磺酸补充剂的抗糖尿病潜力。

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Taurine rescues pancreatic β-cell stress by stimulating α-cell transdifferentiation

The semi-essential ubiquitous amino acid taurine has been shown to alleviate obesity and hyperglycemia in humans; however, the pathways underlying the antidiabetic actions have not been characterized. We explored the effect of chronic taurine exposure on cell biology of pancreatic islets, in degenerative type 1-like diabetes. The latter was modeled by small dose of streptozotocin (STZ) injection for 5 days in mice, followed by a 10-day administration of taurine (2% w/v, orally) in the drinking water. Taurine treatment opposed the detrimental changes in islet morphology and β-/α-cell ratio, induced by STZ diabetes, coincidentally with a significant 3.9 ± 0.7-fold enhancement of proliferation and 40 ± 5% reduction of apoptosis in β-cells. In line with these findings, the treatment counteracted an upregulation of antioxidant (Sod1, Sod2, Cat, Gpx1) and downregulation of islet expansion (Ngn3, Itgb1) genes induced by STZ, in a pancreatic β-cell line. At the same time, taurine enhanced the transdifferentiation of α-cells into β-cells by 2.3 ± 0.8-fold, echoed in strong non-metabolic elevation of cytosolic Ca²⁺ levels in pancreatic α-cells. Our data suggest a bimodal effect of dietary taurine on islet β-cell biology, which combines the augmentation of α-/β-cell transdifferentiation with downregulation of apoptosis. The dualism of action, stemming presumably from the intra- and extracellular modality of the signal, is likely to explain the antidiabetic potential of taurine supplementation.

更新日期：2023-01-30

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