title: Geniposide acutely stimulates insulin secretion in pancreatic β-cells by regulating GLP-1 receptor/cAMP signaling and ion channels.
abstract: Geniposide, an iridoid glycoside, has antidiabetic effects. The present study aimed to evaluate whether geniposide has direct effects on insulin secretion from rat pancreatic islets. The results demonstrated that geniposide potentiated insulin secretion via activating the glucagon-like-1 receptor (GLP-1R) as well as the adenylyl cyclase (AC)/cAMP signaling pathway. Inhibition of protein kinase A (PKA) suppressed the insulinotropic effect of geniposide. Geniposide also inhibited voltage-dependent potassium (Kv) channels, and this effect could be attenuated by inhibition of GLP-1R or PKA. Current-clamp recording showed that geniposide prolonged action potential duration. These results collectively imply that inhibition of Kv channels is linked to geniposide-potentiated insulin secretion by acting downstream of the GLP-1R/cAMP/PKA signaling pathway. Moreover, activation of Ca(2+) channels by geniposide was observed, indicating that the Ca(2+) channel is also an important player in the geniposide effects. Together, these findings provide new insight into the mechanism underlying geniposide-regulated insulin secretion.
authors.affiliation: Department of Pharmacology, Shanxi Medical University, Taiyuan, China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, China. Electronic address: yizhang313@163.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Shanxi Medical University, Taiyuan, China.
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Pharmacology, Shanxi Medical University, Taiyuan, China.
authors.forename: Xiangqin
authors.initials: X
authors.lastname: Zhong
authors.affiliation: Department of Pharmacology, Shanxi Medical University, Taiyuan, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Department of Pharmacology, Shanxi Medical University, Taiyuan, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Shanxi Medical University, Taiyuan, China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, China.
authors.forename: Jingying
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Endocrinology, The First Hospital of Shanxi Medical University, Shanxi Medical University, Taiyuan, China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Bai
authors.affiliation: Department of Pharmacology, Shanxi Medical University, Taiyuan, China.
authors.forename: Lele
authors.initials: L
authors.lastname: Ren
authors.affiliation: Department of Pharmacology, Shanxi Medical University, Taiyuan, China.
authors.forename: Yangyan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, China.
authors.forename: Xiangying
authors.initials: X
authors.lastname: Jiao
authors.affiliation: Department of Endocrinology, The First Hospital of Shanxi Medical University, Shanxi Medical University, Taiyuan, China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000378:metabolism*; D039823:Iridoids / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D015221:Potassium Channels / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D007473:Ion Channels; D039823:Iridoids; D007546:Isoquinolines; D015221:Potassium Channels; D013449:Sulfonamides; C007835:geniposide; D019789:Tetraethylammonium; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
keywords: GLP-1 receptor; Geniposide; Insulin secretion; Voltage-dependent potassium channels; cAMP