ArticleACS synthetic biology2024
Light-Mediated Enhancement of Glucose-Stimulated Insulin Release of Optogenetically Engineered Human Pancreatic Beta-Cells.
Article in ACS synthetic biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 5 citations in OpenAlex.
- Bioengineering Pancreatic Organoids and iPSC-Derived β-Cells for Diabetes: Materials, Devices, and Translational Challenges.Bioengineering (Basel, Switzerland) · 2026Review
- From Insulin Measurement to Partial Exocytosis Model: Advances in Single Pancreatic Beta Cell Amperometry over Four Decades.ACS measurement science au · 2024Review
- Optogenetics in Pancreatic Islets: Actuators and Effects.Diabetes · 2024Review
- An Integrated Optogenetic and Bioelectronic Platform for Regulating Cardiomyocyte Function.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Enhancement of glucose-stimulated insulin secretion (GSIS) in exogenously delivered pancreatic β-cells is desirable, for example, to overcome the insulin resistance manifested in type 2 diabetes or to reduce the number of β-cells for supporting homeostasis of blood sugar in type 1 diabetes. Optogenetically engineered cells can potentiate their function with exposure to light. Given that cyclic adenosine monophosphate (cAMP) mediates GSIS, we surmised that optoamplification of GSIS is feasible in human β-cells carrying a photoactivatable adenylyl cyclase (PAC). To this end, human EndoC-βH3 cells were engineered to express a blue-light-activated PAC, and a workflow was established combining the scalable manufacturing of pseudoislets (PIs) with efficient adenoviral transduction, resulting in over 80% of cells carrying PAC. Changes in intracellular cAMP and GSIS were determined with the photoactivation of PAC in vitro as well as after encapsulation and implantation in mice with streptozotocin-induced diabetes. cAMP rapidly rose in β-cells expressing PAC with illumination and quickly declined upon its termination. Light-induced amplification in cAMP was concomitant with a greater than 2-fold GSIS vs β-cells without PAC in elevated glucose. The enhanced GSIS retained its biphasic pattern, and the rate of oxygen consumption remained unchanged. Diabetic mice receiving the engineered β-cell PIs exhibited improved glucose tolerance upon illumination compared to those kept in the dark or not receiving cells. The findings support the use of optogenetics for molecular customization of the β-cells toward better treatments for diabetes without the adverse effects of pharmacological approaches.
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