Sildenafil amplifies calcium influx and insulin secretion in pancreatic β cells

• DOI: 10.14814/phy2.16091
• Publication Date: 2024-06-12T01:10:19Z
• Authors: Naoya Murao; Risa Morikawa; Yusuke Seino; Kenju Shimomura; Yuko Maejima; Yuichiro Yamada; Atsushi Suzuki
• Keywords: 0301 basic medicine; insulin secretion; diabetes; Physiology; sildenafil; pancreatic β cells; Original Articles; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate; Cell Line; Mice; 03 medical and health sciences; Insulin-Secreting Cells; Insulin Secretion; QP1-981; Animals; Insulin; Calcium; voltage‐dependent calcium channels

Abstract Sildenafil, a phosphodiesterase‐5 (PDE5) inhibitor, has been shown to improve insulin sensitivity in animal models and prediabetic patients. However, its other metabolic effects remain poorly investigated. This study examines the impact of sildenafil on secretion MIN6‐K8 mouse clonal β cells. Sildenafil amplified by enhancing Ca 2+ influx. These required depolarizing stimuli cells but not K ATP channel‐deficient cells, which were already depolarized, indicating that sildenafil‐amplified is depolarization‐dependent channel‐independent. Interestingly, was inhibited pharmacological inhibition R‐type channels, types voltage‐dependent channels (VDCCs). Furthermore, barely affected when effect cyclic GMP PDE5 knockdown. Thus, stimulates influx through VDCCs independently PDE5/cGMP pathway, mechanism differs from known pharmacology conventional secretory pathways. Our results reposition as an insulinotropic agent can be used potential antidiabetic medicine tool elucidate novel secretion.