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.