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- W2996619161 abstract "Abstract Relatively little is known about regulated glucagon secretion by human islet α cells compared to insulin secretion from β cells, despite conclusive evidence of dysfunction in both cell types in diabetes mellitus. Distinct insulin sequences in humans and mice permit in vivo studies of β cell regulation after human islet transplantation in immunocompromised mice, whereas identical glucagon sequences prevent analogous in vivo measures of glucagon output from human α cells. We used CRISPR/Cas9 genome editing to remove glucagon-encoding codons 2-29 in immunocompromised ( NSG ) mice, preserving production of other proglucagon-derived hormones, like Glucagon-like-peptide 1. These NSG- Glucagon knockout ( NSG-GKO ) mice had phenotypes associated with glucagon signaling deficits, including hypoglycemia, hyperaminoacidemia, hypoinsulinemia, and islet α cell hyperplasia. NSG-GKO host metabolic and islet phenotypes reverted after human islet transplantation, and human islets retained regulated glucagon and insulin secretion. NSG-GKO mice provide an unprecedented resource to investigate unique, species-specific human α cell regulation in vivo ." @default.
- W2996619161 created "2019-12-26" @default.
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- W2996619161 date "2019-12-15" @default.
- W2996619161 modified "2023-09-24" @default.
- W2996619161 title "In vivostudies of glucagon secretion by human islets transplanted in mice" @default.
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- W2996619161 doi "https://doi.org/10.1101/2019.12.15.876920" @default.
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