Galectin-1 impacts on glucose homeostasis by modulating pancreatic insulin release

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.

Galectin-1 prevents pathological vascular remodeling in atherosclerosis and abdominal aortic aneurysm

“…However, residual CV risk persists and new approaches mainly focused on anti-inflammatory agents are being tested (45,46). In this regard, previous studies demonstrated the protective role of rGal-1 treatment in the resolution of acute and chronic inflammatory conditions (47), including AMI (11), autoimmune neuroinflammation (48), inflammatory bowel diseases (49), and diabetes (50,51). In this study, we investigated the role of Gal-1 as a novel therapeutic strategy in two different chronic diseases, such as atherosclerosis and AAA.…”

Galectin-1 in Obesity and Type 2 Diabetes

“…( A ) Circulating galectin-1 levels are elevated in human obesity (~25% higher in obese vs. lean [ 64 ]) and in HFD-fed mice (~50% higher in HFD vs. chow [ 22 ]). ( B ) Circulating galectin-1 is positively associated with serum insulin levels in humans and modulated insulin secretion in mice [ 64 , 80 ]. Further, galectin-1 inversely associates with plasma glucose [ 64 ], but galectin-1 reduced glucose uptake in human adipose cells in vitro [ 15 ].…”

“…Further, galectin-1 inversely associates with plasma glucose [ 64 ], but galectin-1 reduced glucose uptake in human adipose cells in vitro [ 15 ]. Insulin and glucose confer direct stimulatory effects on galectin-1 secretion to cell media from several cell types [ 71 , 77 , 80 , 94 , 95 , 96 ]. Galectin-1 is positively associated with circulating levels of IL-6, TNF-α and CRP [ 47 , 64 ].…”

“…However, at this age there was no alteration in glucose or insulin tolerance. Finally, insulin secretion from pancreatic islets in Lgals1 −/− mice increased synergistically compared to wild-type mice after stimulation with recombinant galectin-1 and glucose [ 80 ].…”

“…Galectin-1 also increases neovascularization and unwanted vascular proliferation in diabetic retinopathy [ 42 , 103 , 104 ]. In the pancreas, galectin-1 has been shown to stimulate insulin secretion in female mice, and circulating galectin-1 is also positively associated with serum insulin in studies in humans [ 47 , 64 , 80 ]. Studies have linked galectin-1 to adipogenesis, and it has been proposed that galectin-1 could directly affect pparg expression [ 23 , 72 ].…”