1774-P: Verapamil Prevents Decline of IGF-1 in Subjects with T1D

We have previously found that the calcium channel blocker and anti-hypertensive, verapamil, promotes functional beta cell mass and improves glucose homeostasis in diabetic mice and in humans with recent-onset type 1 diabetes (T1D). Surprisingly, we also discovered that verapamil reversed the T1D-associated elevation in T-follicular-helper cell markers in peripheral blood monocytes, suggesting that it also has immunomodulatory effects. Now, a global proteomics analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) of serum samples from T1D subjects at baseline and after 1 year of receiving verapamil or placebo identified insulin-like growth factor 1 (IGF-1) as one of the top proteins with significantly changed abundance over time. Specifically, IGF-1 abundance decreased during year 1 after diagnosis in subjects with T1D receiving placebo, which is consistent with the lower IGF-1 levels reported previously in individuals with T1D as compared to age- and sex-matched healthy subjects. Interestingly, this decline was blunted in subjects receiving verapamil. To further confirm the LC-MS/MS results, we also measured patient serum levels of IGF-1 by ELISA. The results were very much in alignment and again revealed significantly decreased IGF-1 levels in the placebo group a year after diagnosis, but no such effect in the verapamil treatment group, suggesting that verapamil prevents the decline of IGF-1 in subjects with T1D. Of note, IGF-1, which is primarily produced in liver, acts on many tissues, including pancreatic islets promoting pathways involved in cell growth, differentiation and glucose metabolism. In beta cells, IGF-1 has also been shown to control apoptosis. Thus, our results reveal yet another previously unappreciated pathway affected by verapamil that may contribute to the beneficial effects observed with this treatment in the context of T1D. Disclosure G.Xu: None. J.Chen: None. B.Lu: None. W.Qian: None. A.Shalev: Other Relationship; TIXiMED. Funding National Institutes of Health (R01DK078752, U01DK120379)