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Updated: Jun 29, 2025
08:32
Application of Genetically Encoded Fluorescent Nitric Oxide (NO•) Probes, the geNOps, for Real-time Imaging of NO• Signals in Single Cells
Published on: March 16, 2017
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β-Cell-selective regulation of gene expression by nitric oxide
Aaron Naatz1, Chay Teng Yeo1, Neil Hogg2
1Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
Summary
Nitric oxide (NO) from inducible nitric oxide synthase (iNOS) impacts insulin secretion by affecting beta-cell gene expression. Beta-cells uniquely respond to a narrow NO concentration range, distinct from other cell types.
Area of Science:
- Cellular and Molecular Biology
- Endocrinology
- Metabolism
Background:
- Nitric oxide (NO), produced by inducible nitric oxide synthase (iNOS), inhibits glucose-stimulated insulin secretion.
- NO interferes with mitochondrial oxidative metabolism, protein synthesis, and DNA integrity in beta-cells.
- Cytokines utilize NO to modulate islet of Langerhans function.
Purpose of the Study:
- To investigate the time- and concentration-dependent effects of NO on the expression of key beta-cell response genes.
- To determine the specific concentration range of NO that elicits a response in beta-cells.
- To compare NO's effects on beta-cells with its effects on other cell types.
Main Methods:
- Treatment of beta-cells with varying concentrations of NO.
- Analysis of gene expression for Gadd45α, Puma, Hmox1, Hsp70, Chop, and Ppargc1α.
- Comparative studies in non-beta-cells including alpha-cells, fibroblasts, and macrophages.
Main Results:
- NO stimulates beta-cell gene expression within a narrow concentration range of approximately 0.5-1 µM, consistent with iNOS production levels.
- Higher NO concentrations (>1 µM) inhibit beta-cell gene expression, linked to suppressed mitochondrial oxidative metabolism.
- Beta-cell responses to NO are selective, differing from the concentration-dependent effects observed in non-beta-cells.
Conclusions:
- Beta-cells exhibit a unique, narrow concentration-dependent sensitivity to NO, crucial for regulating insulin secretion.
- The findings highlight the selective nature of NO signaling in pancreatic beta-cells.
- Understanding this narrow responsive window is vital for comprehending beta-cell function and dysfunction in metabolic diseases.
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