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Publication
TRPM7 is a crucial regulator of pancreatic endocrine development and
high-fat-diet-induced ß-cell proliferation.
Authors Altman MK, Schaub CM, Dadi PK, Dickerson MT, Zaborska KE, Nakhe AY, Graff SM,
Galletta TJ, Amarnath G, Thorson AS, Gu G, Jacobson DA
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal Development (Cambridge, England)
Year 2021
Date Published 8/1/2021
Volume : Pages 148 : Not Specified
PubMed Reference 34345920
Abstract The melastatin subfamily of the transient receptor potential channels (TRPM) are
regulators of pancreatic ß-cell function. TRPM7 is the most abundant islet TRPM
channel; however, the role of TRPM7 in ß-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 a-cell and ß-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 ß-cell hyperplasia under
insulin-resistant conditions. ß-Cell proliferation induced by high-fat diet was
significantly decreased in TRPM7-deficient ß-cells. The endocrine roles of TRPM7
may be influenced by cation flux through the channel, and indeed we found that
TRPM7 ablation altered ß-cell Mg2+ and reduced the magnitude of elevation in
ß-cell Mg2+ during proliferation. Together, these findings revealed that TRPM7
controls pancreatic development and ß-cell proliferation, which is likely due to
regulation of Mg2+ homeostasis.




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