908 © The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com Glycobiology, 2021, vol. 31, no. 8, 908–915 https://doi.org/10.1093/glycob/cwab040 Advance Access Publication Date: 8 May 2021 Communication Translational Glycobiology Editor’s Choice Galectin-1 impacts on glucose homeostasis by modulating pancreatic insulin release Victoria Sundblad 2,† , Isabel A Garcia-Tornadu 2,† , Ana M Ornstein 2 , Verónica C Martínez Allo 2 , Rodrigo Lorenzo 2,3 , Sabrina G Gatto 2 , Rosa M Morales 2 , Julián A Gambarte Tudela 4 , Montana N Manselle Cocco 2 , Diego O Croci 4,5 , Damasia Becu-Villalobos 1,2,‡ , and Gabriel A Rabinovich 2,6,‡ 2 Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de investigaciones Científicas y Técnicas (CONICET), C1428 Ciudad de Buenos Aires, Argentina, 3 Instituto de Ciencias Polares, Recursos Naturales y Ambientes, Universidad Nacional de Tierra del Fuego (ICPA-UNTDF-CONICET), V9410 Ushuaia, Argentina, 4 Instituto de Histología y Embriología de Mendoza (IHEM), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Cuyo, M5502JMA Mendoza, Argentina, 5 Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Cuyo, M5502JMA Mendoza, Argentina, and 6 Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, C1428EGA Ciudad de Buenos Aires, Argentina 1 To whom correspondence should be addressed: Tel: +54-11-4783-2869; e-mail: damabecu@gmail.com † Equal contribution ‡ Co-seniors Received 11 December 2020; Revised 10 April 2021; Accepted 29 April 2021 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 regu- lation. 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 hyper- caloric 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. Key words: galectin-1, glucose homeostasis, insulin, type-2 diabetes mellitus Downloaded from https://academic.oup.com/glycob/article/31/8/908/6272447 by guest on 17 January 2023