Voltage-gated Ca2+ channels (Cav) are essential for pancreatic beta cell function as they mediate Ca2+ influx, which leads to insulin exocytosis. The β3 subunit of Cav (Cavβ3) has been suggested to regulate cytosolic Ca2+ ([Ca2+]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 Cavβ3 overexpression, altered [Ca2+]i dynamics, and impaired insulin secretion upon glucose stimulation. Consequently, in high-fat diet (HFD)-induced diabetes, Cavβ3-deficient (Cavβ3-/-) mice showed improved islet function and enhanced glucose tolerance. Normalization of Cavβ3 expression in ob/ob islets by an antisense oligonucleotide rescued the altered [Ca2+]i dynamics and impaired insulin secretion. Importantly, transplantation of Cavβ3-/- islets into the anterior chamber of the eye improved glucose tolerance in HFD-fed mice. Cavβ3 overexpression in human islets also impaired insulin secretion. We thus suggest that Cavβ3 may serve as a druggable target for diabetes treatment.
Pharmacology, Toxicology and Pharmaceutical Science
2
5%
Other
4
9%
Unknown
10
23%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 34. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 August 2018.
All research outputs
#1,314,372
of 27,788,803 outputs
Outputs from Cell Reports
#2,832
of 14,275 outputs
Outputs of similar age
#24,934
of 345,134 outputs
Outputs of similar age from Cell Reports
#75
of 314 outputs
Altmetric has tracked 27,788,803 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 95th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 14,275 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 29.0. This one has done well, scoring higher than 80% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 345,134 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 92% of its contemporaries.
We're also able to compare this research output to 314 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 76% of its contemporaries.
