Pharmacological polysulfide suppresses glucose-stimulated insulin secretion in an ATP-sensitive potassium channel-dependent manner

• Published in: Scientific reports 2019-12, Vol.9 (1), p.19377-12, Article 19377
• Main Authors: Shoji, Tomohiro, Hayashi, Mikio, Sumi, Chisato, Kusunoki, Munenori, Uba, Takeo, Matsuo, Yoshiyuki, Kimura, Hideo, Hirota, Kiichi
• Format: Article
• Language: English
• Subjects: 13/31; 631/80/304; 692/163/2743/137/138; 9/74; Adenosine Triphosphate - metabolism; Animals; ATP; Blood glucose; Blood pressure; Calcium - metabolism; Cell Line; Glucose; Glucose - metabolism; Glucose - pharmacology; Humanities and Social Sciences; Humans; Hydrogen sulfide; Hydrogen Sulfide - metabolism; Insulin; Insulin - biosynthesis; Insulin - metabolism; Insulin secretion; Insulin Secretion - drug effects; Insulin Secretion - genetics; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; Insulin-Secreting Cells - pathology; KATP Channels - antagonists & inhibitors; KATP Channels - metabolism; Mice; multidisciplinary; Oxygen - metabolism; Potassium; Rats; Science; Science (multidisciplinary); Signal Transduction - drug effects; Smooth muscle; Sulfides - pharmacology; Sulfur
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-55848-7

Hydrogen sulfide (H 2 S) is an endogenous gaseous transmitter synthesized in various cell types. It is well established that H 2 S functions in many physiological processes, including the relaxation of vascular smooth muscle, mediation of neurotransmission, regulation of inflammation, and modulation of insulin signaling. In recent years, it has been revealed that polysulfides, substances with a varying number of sulfur atoms (H 2 Sn), are generated endogenously from H 2 S in the presence of oxygen. A series of studies describes that sulfane sulfur has the unique ability to bind reversibly to other sulfur atoms to form hydropersulfides and polysulfides, and that polysulfides activate ion channels and promote calcium influx. Furthermore, polysulfides regulate tumor suppressor activity, promote the activation of transcription factors targeting antioxidant genes and regulate blood pressure by vascular smooth muscle relaxation. Insulin secretion from pancreatic β cells plays a critical role in response to increased blood glucose concentration. H 2 S has emerged as an important regulator of glycemic control and exhibits characteristic regulation of glucose homeostasis. However, the effects of polysulfides on glucose-stimulated insulin secretion (GSIS) are largely unknown. In this study, we demonstrated that pharmacological polysulfide salts including Na 2 S 2 , Na 2 S 3 , and Na 2 S 4 considerably inhibit GSIS in mouse and rat pancreatic β-cell-derived MIN6 and INS-1 cell lines, and that the effect is dependent on the activation of ATP-sensitive potassium channels. In addition, we demonstrated that a mixture of Na 2 S and diethylamine NONOate inhibits GSIS in a similar way to the pharmacological administration of polysulfide salts.