Galectin-3 impairs calcium transients and β-cell function

Area of Science:

• Endocrinology
• Immunology
• Metabolic disease research

Background:

• Macrophages and inflammation are increased in pancreatic islets during diabetes, correlating with beta-cell dysfunction.
• Galectin-3 (Gal3), primarily from macrophages, is elevated in islets of high-fat diet (HFD)-fed and diabetic db/db mice.

Purpose of the Study:

• To investigate the role of galectin-3 (Gal3) in pancreatic beta-cell dysfunction and its potential as a therapeutic target for type 2 diabetes.

Main Methods:

• Assessed Gal3 levels in islets from HFD-fed and db/db mice.
• Examined the effect of Gal3 on glucose-stimulated insulin secretion (GSIS) in vitro and in vivo.
• Investigated the interaction between Gal3 and calcium voltage-gated channel auxiliary subunit gamma 1 (CACNG1).
• Evaluated the impact of Gal3 inhibition on glucose homeostasis in mouse models.

Main Results:

• Gal3 acutely reduces GSIS in mouse and human beta-cell lines and primary islets.
• Gal3 binds to CACNG1, inhibiting calcium influx and subsequent GSIS.
• Beta-cell-specific CACNG1 deficiency mimics Gal3 treatment effects.
• Genetic or pharmacologic inhibition of Gal3 significantly improves GSIS and glucose homeostasis in HFD-fed and db/db mice.

Conclusions:

• Galectin-3 plays a critical role in pancreatic beta-cell dysfunction associated with type 2 diabetes.
• Gal3's mechanism involves inhibiting calcium influx via CACNG1.
• Inhibition of Gal3 presents a promising therapeutic strategy for improving glucose homeostasis in type 2 diabetes.