TRPM7 is a crucial regulator of pancreatic endocrine development and high-fat-diet-induced β-cell proliferation.

Abstract

The melastatin subfamily of the transient receptor potential channels (TRPM) are regulators of pancreatic β-cell function. TRPM7 is the most abundant islet TRPM channel; however, the role of TRPM7 in β-cell function has not been determined. Here, we used various spatiotemporal transgenic mouse models to investigate how TRPM7 knockout influences pancreatic endocrine development, proliferation and function. Ablation of TRPM7 within pancreatic progenitors reduced pancreatic size, and α-cell and β-cell mass. This resulted in modestly impaired glucose tolerance. However, TRPM7 ablation following endocrine specification or in adult mice did not impact endocrine expansion or glucose tolerance. As TRPM7 regulates cell proliferation, we assessed how TRPM7 influences β-cell hyperplasia under insulin-resistant conditions. β-Cell proliferation induced by high-fat diet was significantly decreased in TRPM7-deficient β-cells. The endocrine roles of TRPM7 may be influenced by cation flux through the channel, and indeed we found that TRPM7 ablation altered β-cell Mg2+ and reduced the magnitude of elevation in β-cell Mg2+ during proliferation. Together, these findings revealed that TRPM7 controls pancreatic development and β-cell proliferation, which is likely due to regulation of Mg2+ homeostasis.

• Authors: Molly K Altman, Charles M Schaub, Prasanna K Dadi, Matthew T Dickerson, Karolina E Zaborska, Arya Y Nakhe, Sarah M Graff, Thomas J Galletta, Gautami Amarnath, Ariel S Thorson, Guoqiang Gu, David A Jacobson
• Journal: Development (Cambridge, England) (Development) Vol. 148 Issue 16 (08 15 2021) ISSN: 1477-9129 [Electronic] England
• PMID: 34345920 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. Published by The Company of Biologists Ltd.

Chemical References

• Insulin
• TRPM Cation Channels
• Trpm7 protein, mouse
• Magnesium

Topics

• Animals
• Cell Proliferation (genetics)
• Cells, Cultured
• Diet, High-Fat
• Gene Knockout Techniques
• Glucose Intolerance (genetics)
• Homeostasis (genetics)
• Insulin (metabolism)
• Insulin Secretion (genetics)
• Insulin-Secreting Cells (metabolism)
• Magnesium (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Pancreas (growth & development, metabolism)
• TRPM Cation Channels (genetics, metabolism)