Galectin-3 impairs calcium transients and ß-cell function.
Nat Commun
; 15(1): 3682, 2024 May 01.
Article
in En
| MEDLINE
| ID: mdl-38693121
ABSTRACT
In diabetes, macrophages and inflammation are increased in the islets, along with ß-cell dysfunction. Here, we demonstrate that galectin-3 (Gal3), mainly produced and secreted by macrophages, is elevated in islets from both high-fat diet (HFD)-fed and diabetic db/db mice. Gal3 acutely reduces glucose-stimulated insulin secretion (GSIS) in ß-cell lines and primary islets in mice and humans. Importantly, Gal3 binds to calcium voltage-gated channel auxiliary subunit gamma 1 (CACNG1) and inhibits calcium influx via the cytomembrane and subsequent GSIS. ß-Cell CACNG1 deficiency phenocopies Gal3 treatment. Inhibition of Gal3 through either genetic or pharmacologic loss of function improves GSIS and glucose homeostasis in both HFD-fed and db/db mice. All animal findings are applicable to male mice. Here we show a role of Gal3 in pancreatic ß-cell dysfunction, and Gal3 could be a therapeutic target for the treatment of type 2 diabetes.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Galectin 3
/
Insulin-Secreting Cells
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Diet, High-Fat
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Insulin Secretion
Limits:
Animals
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Humans
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Male
Language:
En
Journal:
Nat Commun
/
Nature communications
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: