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Malvidin-3-glucoside induces insulin secretion by activating the PLC/IP3 pathway and enhancing Ca2+ influx in INS-1 pancreatic β-cells
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作者:

Channuwong, Pilailak
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Chulalongkorn Univ, Fac Allied Hlth Sci, Ctr Excellence Phytochem & Funct Food Clin Nutr, Dept Nutr & Dietet, Bangkok 10330, Thailand
Oklahoma State Univ, Coll Vet Med, Dept Physiol Sci, Stillwater, OK 74078 USA Chulalongkorn Univ, Fac Allied Hlth Sci, Ctr Excellence Phytochem & Funct Food Clin Nutr, Dept Nutr & Dietet, Bangkok 10330, Thailand

Yuan, Yuanying
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Louisiana State Univ, Sch Vet Med, Dept Comparat Biomed Sci, Baton Rouge, LA 70803 USA Chulalongkorn Univ, Fac Allied Hlth Sci, Ctr Excellence Phytochem & Funct Food Clin Nutr, Dept Nutr & Dietet, Bangkok 10330, Thailand

Yao, Shaomian
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Louisiana State Univ, Sch Vet Med, Dept Comparat Biomed Sci, Baton Rouge, LA 70803 USA Chulalongkorn Univ, Fac Allied Hlth Sci, Ctr Excellence Phytochem & Funct Food Clin Nutr, Dept Nutr & Dietet, Bangkok 10330, Thailand

Bauermann, Fernando Vicosa
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Oklahoma State Univ, Coll Vet Med, Dept Vet Pathobiol, Stillwater, OK 74078 USA Chulalongkorn Univ, Fac Allied Hlth Sci, Ctr Excellence Phytochem & Funct Food Clin Nutr, Dept Nutr & Dietet, Bangkok 10330, Thailand

Cheng, Henrique
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Oklahoma State Univ, Coll Vet Med, Dept Physiol Sci, Stillwater, OK 74078 USA Chulalongkorn Univ, Fac Allied Hlth Sci, Ctr Excellence Phytochem & Funct Food Clin Nutr, Dept Nutr & Dietet, Bangkok 10330, Thailand

Suantawee, Tanyawan
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Chulalongkorn Univ, Fac Allied Hlth Sci, Ctr Excellence Phytochem & Funct Food Clin Nutr, Dept Nutr & Dietet, Bangkok 10330, Thailand Chulalongkorn Univ, Fac Allied Hlth Sci, Ctr Excellence Phytochem & Funct Food Clin Nutr, Dept Nutr & Dietet, Bangkok 10330, Thailand

Adisakwattana, Sirichai
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Chulalongkorn Univ, Fac Allied Hlth Sci, Ctr Excellence Phytochem & Funct Food Clin Nutr, Dept Nutr & Dietet, Bangkok 10330, Thailand Chulalongkorn Univ, Fac Allied Hlth Sci, Ctr Excellence Phytochem & Funct Food Clin Nutr, Dept Nutr & Dietet, Bangkok 10330, Thailand
机构:
[1] Chulalongkorn Univ, Fac Allied Hlth Sci, Ctr Excellence Phytochem & Funct Food Clin Nutr, Dept Nutr & Dietet, Bangkok 10330, Thailand
[2] Oklahoma State Univ, Coll Vet Med, Dept Physiol Sci, Stillwater, OK 74078 USA
[3] Louisiana State Univ, Sch Vet Med, Dept Comparat Biomed Sci, Baton Rouge, LA 70803 USA
[4] Oklahoma State Univ, Coll Vet Med, Dept Vet Pathobiol, Stillwater, OK 74078 USA
关键词:
Malvidin-3-glucoside;
Pancreatic beta-cells;
Insulin secretion;
Calcium signals;
L-type voltage-dependent Ca2+ channels;
PLC/IP3;
GENE-EXPRESSION;
CHANNELS;
HYPERGLYCEMIA;
MODULATION;
VIABILITY;
MECHANISM;
CALCIUM;
ACID;
D O I:
10.1038/s41598-025-95808-y
中图分类号:
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
Malvidin-3-glucoside (M3G), an anthocyanin found in blueberries and grapes, shows promise as a natural anti-diabetic agent. However, its effect on insulin secretion and its underlying mechanisms remains unclear. This study investigated the impact of M3G on beta-cells (INS-1) through real-time Ca2+ imaging and insulin secretion assays. M3G increased intracellular Ca2+ levels in a concentration-dependent manner, specifically targeting beta-cells without affecting other pancreatic cell types. It enhanced insulin secretion under both basal (4 mM) and stimulatory (11 mM) glucose conditions while maintaining cell viability at concentrations up to 100 mu M. Pharmacological inhibitors revealed that M3G-induced Ca2+ signals resulted from both Ca influx through L-type voltage-dependent calcium channels (L-type VDCCs) and Ca2+ release from the endoplasmic reticulum (ER) via the PLC/IP3 pathway. Nimodipine, an L-type VDCC blocker, inhibited M3G-induced Ca2+ influx, while U73122 (a PLC inhibitor) and 2-aminoethoxydiphenyl borate (2-APB), an IP3 receptor blocker, suppressed Ca2+ release from the ER. Additionally, M3G upregulated the expression of key glucose-stimulated insulin secretion (GSIS)-related genes, including Ins1 (insulin), Slc2a2 (GLUT2), and Gck (glucokinase). These findings suggest that M3G stimulates insulin secretion by promoting Ca2+ influx through L-type VDCCs, facilitating Ca2+ release from the ER, and upregulating GSIS-related genes. M3G holds promise as a natural anti-diabetic agent by enhancing insulin secretion and supporting beta-cell function.
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Hop Lariboisiere, Dept Internal Med B, AP HP, F-75010 Paris, France
Univ Paris 07, F-75005 Paris, France Hop Lariboisiere, Dept Internal Med B, AP HP, F-75010 Paris, France

Virally, M.
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Hop Lariboisiere, Dept Internal Med B, AP HP, F-75010 Paris, France
Univ Paris 07, F-75005 Paris, France Hop Lariboisiere, Dept Internal Med B, AP HP, F-75010 Paris, France

Laloi-Michelin, M.
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Hop Lariboisiere, Dept Internal Med B, AP HP, F-75010 Paris, France
Univ Paris 07, F-75005 Paris, France Hop Lariboisiere, Dept Internal Med B, AP HP, F-75010 Paris, France

Medeau, V.
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Hop Lariboisiere, Dept Internal Med B, AP HP, F-75010 Paris, France Hop Lariboisiere, Dept Internal Med B, AP HP, F-75010 Paris, France

Kevorkian, J. -P.
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Hop Lariboisiere, Dept Internal Med B, AP HP, F-75010 Paris, France
Univ Paris 07, F-75005 Paris, France Hop Lariboisiere, Dept Internal Med B, AP HP, F-75010 Paris, France