Disruption of Galectin-1 Impairs Glucose Homeostasis and Increases Food Intake in Female Mice

ISABEL ANDREA GARCIA-TORNADU; VICTORIA SUNDBLAD; NICOLÁS GILIO; DAMASIA BECU-VILLALOBOS

Chicago

Congreso; Endocrine Society's 96th Annual Meeting and Expo; 2014

Endocrine Society's

Type 2 diabetes is a disease of impaired glucose homeostasis and insulin action with an etiology that encompasses genetic, cellular and environmental factors. Recent observations suggest that a deficiency of beta cell protein glycosylation and glucose transport may underly a pathogenic pathway leading to diabetes. It has been proposed that galectins, a family of endogenous glycan-binding proteins, may stabilize glucose transporters of beta cells at the cell surface, extending their half-life. In this context, we studied the effect of disruption of galectin 1 on glucose homeostasis and insulin sensitivity using galectin 1 (Gal1-/-) knockout mice. Body weight and food intake were increased at 2 and 6 months of age in female Gal1 -/- mice. Fasted glucose levels were high in 6 month old females (p < 0.04), and glucose intolerance to an ip administration of 2g/kg was evidenced. On the other hand, insulin sensitivity was preserved, but already at 2 months of age fasted serum insulin levels were decreased and glucose (3g/kg) -stimulated insulin secretion was greatly diminished in the female mutant model. Blunted response correlated with an increase in pancreatic insulin content at 2 and 6 months of age (P<0.02). Surprisingly, male Gal1-/- mice presented normal body weight, food intake, and glucose tolerance. These results point to an altered insulin secretory response in the transgenic mouse, and highlight a sex-biased contribution of galectin 1 to critical biological events which regulate glucose homeostasis. Nothing to Disclose: IAG, VS, NG, GAR, DB