Optogenetic control of insulin secretion by pancreatic β-cells in vitro and in vivo.

Abstract

The present study assessed the ability of optogenetics techniques to provide a better understanding of the control of insulin secretion, particularly regarding pancreatic β-cell function in homeostasis and pathological conditions such as diabetes mellitus (DM). We used optogenetics to investigate whether insulin secretion and blood glucose homeostasis could be controlled by regulating intracellular calcium ion concentrations ([Ca(2+)]i) in a mouse pancreatic β-cell line (MIN6) transfected with the optogenetic protein channelrhodopsin-2 (ChR2). The ChR2-transfected MIN6 (ChR2-MIN6) cells secreted insulin following irradiation with a laser (470 nm). The increase in [Ca(2+)]i was accompanied by elevated levels of messenger RNAs that encode calcium/calmodulin-dependent protein kinase II delta and adenylate cyclase 1. ChR2-MIN6 cells suspended in matrigel were inoculated into streptozotocin-induced diabetic mice that were then subjected to a glucose tolerance test. Laser irradiation of these mice caused a significant decrease in blood glucose, and the irradiated implanted cells expressed insulin. These findings demonstrate the power of optogenetics to precisely and efficiently controlled insulin secretion by pancreatic β-cells 'on demand', in contrast to techniques using growth factors or chemical inducers. Optogenetic technology shows great promise for understanding the mechanisms of glucose homeostasis and for developing treatments for metabolic diseases such as DM.

• Authors: T Kushibiki, S Okawa, T Hirasawa, M Ishihara
• Journal: Gene therapy (Gene Ther) Vol. 22 Issue 7 Pg. 553-9 (Jul 2015) ISSN: 1476-5462 [Electronic] England
• PMID: 25809465 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Channelrhodopsins
• Insulin
• Streptozocin
• Calcium-Calmodulin-Dependent Protein Kinase Type 2
• Camk2d protein, mouse
• Adenylyl Cyclases
• adenylyl cyclase 1
• Calcium

Topics

• Adenylyl Cyclases (metabolism)
• Animals
• Blood Glucose (metabolism)
• Calcium (metabolism)
• Calcium-Calmodulin-Dependent Protein Kinase Type 2 (metabolism)
• Cells, Cultured
• Channelrhodopsins
• Diabetes Mellitus, Experimental (metabolism, radiotherapy)
• Insulin (metabolism)
• Insulin Secretion
• Insulin-Secreting Cells (metabolism, radiation effects)
• Low-Level Light Therapy (methods)
• Mice
• Optogenetics
• Streptozocin