The beneficial effects of a muscarinic agonist on pancreatic β-cells

被引:9
作者
Ito, Yuzuru [1 ]
Kaji, Mitsuyo [1 ]
Sakamoto, Eri [1 ]
Terauchi, Yasuo [1 ]
机构
[1] Yokohama City Univ, Dept Endocrinol & Metab, Grad Sch Med, Yokohama, Kanagawa, Japan
关键词
ACETYLCHOLINE-RECEPTORS; GLUCOSE-HOMEOSTASIS; INSULIN-SECRETION; EXPRESSION; PROLIFERATION; GLUCOKINASE; HYPERPLASIA; ACTIVATION; GROWTH; MICE;
D O I
10.1038/s41598-019-52691-8
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
The brain and nervous system play an important role in pancreatic beta-cell function. This study investigated the role of muscarinic agonists or acetylcholine, which is the major neurotransmitter in the vagal nerve, in regulating pancreatic beta-cell mass and glucose homeostasis. Administration of the muscarinic agonist bethanechol increased insulin secretion and improved glucose tolerance in insulin-receptor substrate 2 (IRS2)-knockout (IRS-2(-/-)) mice and diet-induced obesity mice. Oral administration of bethanechol increased beta-cell mass and proliferation in wild-type mice, but not IRS-2-/- mice. The muscarinic agonist also increased the incorporation of 5-bromo-2'-deoxyuridine (BrdU) into islets isolated from wild-type mice and pancreatic beta-cell line MIN6. The phosphorylation of protein kinase B (Akt) induced by oral administration of bethanechol was observed in wild-type mice, but not IRS-2(-/-) mice. The secretion of glucagon-like peptide-1 (GLP-1) was also stimulated by bethanechol in wild-type mice, and a GLP-1 antagonist partially inhibited the bethanechol-induced increase in beta-cell mass. These results suggest that the muscarinic agonist exerted direct and indirect effects on beta-cell proliferation that were dependent on the IRS-2/Akt pathway. The bethanechol-stimulated release of GLP-1 may be indirectly associated with beta-cell proliferation.
引用
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页数:12
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