AI Article Synopsis
- Sildenafil improves insulin sensitivity and enhances insulin secretion in β cells, particularly in the presence of other depolarizing stimuli.
- The drug operates independently of the traditional PDE5/cGMP pathway, primarily by increasing calcium influx through R-type voltage-dependent calcium channels.
- This study positions sildenafil as a potential antidiabetic medication and provides insights into a novel mechanism for insulin secretion.
Article 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 insulin secretion in MIN6-K8 mouse clonal β cells. Sildenafil amplified insulin secretion by enhancing Ca influx. These effects required other depolarizing stimuli in MIN6-K8 cells but not in K channel-deficient β cells, which were already depolarized, indicating that sildenafil-amplified insulin secretion is depolarization-dependent and K channel-independent. Interestingly, sildenafil-amplified insulin secretion was inhibited by pharmacological inhibition of R-type channels, but not of other types of voltage-dependent Ca channels (VDCCs). Furthermore, sildenafil-amplified insulin secretion was barely affected when its effect on cyclic GMP was inhibited by PDE5 knockdown. Thus, sildenafil stimulates insulin secretion and Ca influx through R-type VDCCs independently of the PDE5/cGMP pathway, a mechanism that differs from the known pharmacology of sildenafil and conventional insulin secretory pathways. Our results reposition sildenafil as an insulinotropic agent that can be used as a potential antidiabetic medicine and a tool to elucidate the novel mechanism of insulin secretion.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11166479 | PMC |
| http://dx.doi.org/10.14814/phy2.16091 | DOI Listing |
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