Journal
BIOPHYSICAL JOURNAL
Volume 105, Issue 1, Pages 29-39Publisher
CELL PRESS
DOI: 10.1016/j.bpj.2013.05.036
Keywords
-
Categories
Funding
- National Institutes of Health [DK31842]
- Canadian Institutes for Health Research [MOP-119537]
- Lundbeck Foundation
Ask authors/readers for more resources
Glucose-stimulated insulin secretion is pulsatile and driven by intrinsic oscillations in metabolism, electrical activity, and Ca2+ in pancreatic islets. Periodic variations in glucose can entrain islet Ca2+ and insulin secretion, possibly promoting interislet synchronization. Here, we used fluorescence microscopy to demonstrate that glucose oscillations can induce distinct 1:1 and 1:2 entrainment of oscillations (one and two oscillations for each period of exogenous stimulus, respectively) in islet Ca2+, NAD(P) H, and mitochondrial membrane potential. To our knowledge, this is the first demonstration of metabolic entrainment in islets, and we found that entrainment of metabolic oscillations requires voltage-gated Ca2+ influx. We identified diverse patterns of 1:2 entrainment and showed that islet synchronization during entrainment involves adjustments of both oscillatory phase and period. All experimental findings could be recapitulated by our recently developed mathematical model, and simulations suggested that interislet variability in 1:2 entrainment patterns reflects differences in their glucose sensitivity. Finally, our simulations and recordings showed that a heterogeneous group of islets synchronized during 1:2 entrainment, resulting in a clear oscillatory response from the collective. In summary, we demonstrate that oscillatory glucose can induce complex modes of entrainment of metabolically driven oscillations in islets, and provide additional support for the notion that entrainment promotes interislet synchrony in the pancreas.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available