The NERP-4–SNAT2 axis regulates pancreatic β-cell maintenance and function.

Autor: Zhang, Weidong, Miura, Ayako, Abu Saleh, Md Moin, Shimizu, Koichiro, Mita, Yuichiro, Tanida, Ryota, Hirako, Satoshi, Shioda, Seiji, Gmyr, Valery, Kerr-Conte, Julie, Pattou, Francois, Jin, Chunhuan, Kanai, Yoshikatsu, Sasaki, Kazuki, Minamino, Naoto, Sakoda, Hideyuki, Nakazato, Masamitsu
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Zdroj: Nature Communications; 12/9/2023, Vol. 14 Issue 1, p1-21, 21p
Abstrakt: Insulin secretion from pancreatic β cells is regulated by multiple stimuli, including nutrients, hormones, neuronal inputs, and local signalling. Amino acids modulate insulin secretion via amino acid transporters expressed on β cells. The granin protein VGF has dual roles in β cells: regulating secretory granule formation and functioning as a multiple peptide precursor. A VGF-derived peptide, neuroendocrine regulatory peptide-4 (NERP-4), increases Ca2+ influx in the pancreata of transgenic mice expressing apoaequorin, a Ca2+-induced bioluminescent protein complex. NERP-4 enhances glucose-stimulated insulin secretion from isolated human and mouse islets and β-cell–derived MIN6-K8 cells. NERP-4 administration reverses the impairment of β-cell maintenance and function in db/db mice by enhancing mitochondrial function and reducing metabolic stress. NERP-4 acts on sodium-coupled neutral amino acid transporter 2 (SNAT2), thereby increasing glutamine, alanine, and proline uptake into β cells and stimulating insulin secretion. SNAT2 deletion and inhibition abolish the protective effects of NERP-4 on β-cell maintenance. These findings demonstrate a novel autocrine mechanism of β-cell maintenance and function that is mediated by the peptide–amino acid transporter axis. Amino acids modulate insulin secretion via amino acid transporters expressed on β cells. Here, the authors show a VGF-derived peptide NERP-4 acts as a positive allosteric modulator on the amino acid transporter SNAT2/SLC38A2, thereby contributing to β-cell maintenance and function. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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