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ACS Synth Biol. 2019 Oct 18;8(10):2248-2255. doi: 10.1021/acssynbio.9b00262. Epub 2019 Sep 16.

Amelioration of Diabetes in a Murine Model upon Transplantation of Pancreatic β-Cells with Optogenetic Control of Cyclic Adenosine Monophosphate.

Author information

1
Department of Chemical and Biological Engineering , Tufts University , Medford , Massachusetts 02155 , United States.
2
Clinical and Translational Science Institute , Tufts Medical Center , Boston , Massachusetts 02111 , United States.

Abstract

Pharmacological augmentation of glucose-stimulated insulin secretion (GSIS), for example, to overcome insulin resistance in type 2 diabetes is linked to suboptimal regulation of blood sugar. Cultured β-cells and islets expressing a photoactivatable adenylyl cyclase (PAC) are amenable to GSIS potentiation with light. However, whether PAC-mediated enhancement of GSIS can improve the diabetic state remains unknown. To this end, β-cells were engineered with stable PAC expression that led to over 2-fold greater GSIS upon exposure to blue light while there were no changes in the absence of glucose. Moreover, the rate of oxygen consumption was unaltered despite the photoinduced elevation of GSIS. Transplantation of these cells into streptozotocin-treated mice resulted in improved glucose tolerance, lower hyperglycemia, and higher plasma insulin when subjected to illumination. Embedding optogenetic networks in β-cells for physiologically relevant control of GSIS will enable novel solutions potentially overcoming the shortcomings of current treatments for diabetes.

KEYWORDS:

beta-cells; diabetes; insulin secretion; optogenetics; pancreas; photoactivatable adenylyl cyclase

PMID:
31518106
DOI:
10.1021/acssynbio.9b00262

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