Sundblad Victoria, Garcia-Tornadu Isabel A, Ornstein Ana M, Martínez Allo Verónica C, Lorenzo Rodrigo, Gatto Sabrina G, Morales Rosa M, Gambarte Tudela Julián A, Manselle Cocco Montana N, Croci Diego O, Becu-Villalobos Damasia, Rabinovich Gabriel A
Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de investigaciones Científicas y Técnicas (CONICET), C1428 Ciudad de Buenos Aires, Argentina.
Instituto de Ciencias Polares, Recursos Naturales y Ambientes, Universidad Nacional de Tierra del Fuego (ICPA-UNTDF-CONICET), V9410 Ushuaia, Argentina.
Glycobiology. 2021 Sep 9;31(8):908-915. doi: 10.1093/glycob/cwab040.
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.
2型糖尿病（T2DM）是一个日益严重的全球性健康问题，涉及胰腺β细胞胰岛素分泌缺陷和外周胰岛素抵抗，导致葡萄糖调节受损。半乳糖凝集素-1——一种对含N-乙酰乳糖胺（LacNAc）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因子。然而，尚未探究半乳糖凝集素-1在不依赖高热量饮食的情况下对葡萄糖稳态和胰腺β细胞功能的作用。在此，我们在缺乏半乳糖凝集素-1（Lgals1-/-）的雌性而非雄性小鼠中发现了一种与T2DM相符的表型，涉及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-/-雌性小鼠体重更高，随意进食以及禁食和急性再喂养后的食物摄入量均增加。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-/-雌性小鼠的葡萄糖耐量改变，且根据禁食时间不同基础血糖水平更高。对葡萄糖超载的胰岛素反应受损，而在缺乏半乳糖凝集素-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。我们的研究确定了半乳糖凝集素-1通过调节胰腺胰岛素分泌在调节葡萄糖代谢中的作用，突出了控制T2DM的新机会。
