Abstract

Type-2 diabetes mellitus (T2DM) is an expanding global health problem, involving defective insulin secretion by pancreatic β-cells and peripheral insulin resistance, leading to impaired glucose regulation. Galectin-1—an endogenous lectin with affinity for N-acetyllactosamine (LacNAc)-containing glycans—has emerged as a regulator of inflammatory and metabolic disorders. However, the role of galectin-1 in glucose homeostasis and pancreatic β-cell function, independently of hypercaloric diets, has not been explored. Here, we identified a phenotype compatible with T2DM, involving alterations in glucose metabolism and pancreatic insulin release, in female but not male mice lacking galectin-1 (Lgals1^−/−). Compared with age-matched controls, Lgals1^−/− female mice exhibited higher body weight and increased food intake ad libitum as well as after fasting and acute re-feeding. Although fasted serum insulin levels and insulin sensitivity were similar in both genotypes, Lgals1^−/− female mice presented altered glucose tolerance and higher basal glucose levels depending on the fasting period. Insulin response to glucose overload was impaired, while pancreatic insulin content was enhanced in the absence of galectin-1. Accordingly, recombinant galectin-1 enhanced glucose-stimulated insulin release in vitro. Our study identifies a role for galectin-1 in regulating glucose metabolism through modulation of pancreatic insulin secretion, highlighting novel opportunities to control T2DM.

中文翻译：

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Galectin-1 通过调节胰腺胰岛素释放影响葡萄糖稳态

摘要

2 型糖尿病 (T2DM) 是一个不断扩大的全球健康问题，涉及胰腺 β 细胞的胰岛素分泌缺陷和外周胰岛素抵抗，导致葡萄糖调节受损。Galectin-1——一种对含有N-乙酰乳糖胺 (LacNAc) 的聚糖具有亲和力的内源性凝集素——已成为炎症和代谢紊乱的调节剂。然而，半乳糖凝集素-1在葡萄糖稳态和胰腺β细胞功能中的作用，独立于高热量饮食，尚未被探索。在这里，我们在缺乏 galectin-1 ( Lgals1 ^-/- )的雌性而非雄性小鼠中鉴定了与 T2DM 相容的表型，包括葡萄糖代谢和胰腺胰岛素释放的改变。与年龄匹配的对照组相比，Lgals1 ^-/-雌性小鼠在禁食和急性再喂食后表现出更高的体重和增加的食物摄入量。尽管两种基因型的空腹血清胰岛素水平和胰岛素敏感性相似，但Lgals1 ^-/-雌性小鼠表现出改变的葡萄糖耐量和更高的基础葡萄糖水平，这取决于空腹期。胰岛素对葡萄糖超载的反应受损，而在没有半乳糖凝集素-1 的情况下胰腺胰岛素含量增加。因此，重组半乳糖凝集素-1 在体外增强了葡萄糖刺激的胰岛素释放。我们的研究确定了 galectin-1 通过调节胰腺胰岛素分泌调节葡萄糖代谢的作用，突出了控制 T2DM 的新机会。