| First Author | Lee K | Year | 2018 |
| Journal | Cell Rep | Volume | 24 |
| Issue | 4 | Pages | 922-934 |
| PubMed ID | 30044988 | Mgi Jnum | J:271206 |
| Mgi Id | MGI:6278463 | Doi | 10.1016/j.celrep.2018.06.086 |
| Citation | Lee K, et al. (2018) Blocking Ca(2+) Channel beta3 Subunit Reverses Diabetes. Cell Rep 24(4):922-934 |
| abstractText | Voltage-gated Ca(2+) channels (Cav) are essential for pancreatic beta cell function as they mediate Ca(2+) influx, which leads to insulin exocytosis. The beta3 subunit of Cav (Cavbeta3) has been suggested to regulate cytosolic Ca(2+) ([Ca(2+)]i) oscillation frequency and insulin secretion under physiological conditions, but its role in diabetes is unclear. Here, we report that islets from diabetic mice show Cavbeta3 overexpression, altered [Ca(2+)]i dynamics, and impaired insulin secretion upon glucose stimulation. Consequently, in high-fat diet (HFD)-induced diabetes, Cavbeta3-deficient (Cavbeta3(-/-)) mice showed improved islet function and enhanced glucose tolerance. Normalization of Cavbeta3 expression in ob/ob islets by an antisense oligonucleotide rescued the altered [Ca(2+)]i dynamics and impaired insulin secretion. Importantly, transplantation of Cavbeta3(-/-) islets into the anterior chamber of the eye improved glucose tolerance in HFD-fed mice. Cavbeta3 overexpression in human islets also impaired insulin secretion. We thus suggest that Cavbeta3 may serve as a druggable target for diabetes treatment. |
