Modeling Neonatal Diabetes

Main Category: Diabetes
Also Included In: Genetics;  Pediatrics / Children's Health;  Biology / Biochemistry
Article Date: 09 Dec 2008 - 7:00 PDT

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Neonatal diabetes is a rare form of diabetes that is usually detected within the first six months of life. Approximately 50% of cases of neonatal diabetes are caused by mutations in either the KIR6.2 gene or the SUR1 gene. Frances Ashcroft and colleagues, at Oxford University, United Kingdom, have now developed a mouse model of neonatal diabetes that they believe provides new insight into the human disease.

In the study, mice were engineered to express in the beta-cells of their pancreas a mutant Kir6.2 protein (V59M) that causes neonatal diabetes in humans. These beta-V59M mice developed diabetes soon after birth, and by 5 weeks of age blood glucose levels were markedly increased and the hormone insulin was undetectable, two hallmarks of diabetes. This was because beta-cells of the pancreas were secreting less insulin as a result of the mutant Kir6.2 protein, which forms a complex known as a KATP channel with the protein made from the SUR1 gene. When pancreata from 5 week old beta-V59M mice were treated with a drug that inhibits KATP channel activity, beta-cells of the pancreata started secreting insulin again. Thus, expression of the V59M mutant Kir6.2 in mouse pancreatic beta cells alone is sufficient to recapitulate human neonatal diabetes.

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TITLE: Expression of an activating mutation in the gene encoding the KATP channel subunit Kir6.2 in mouse pancreatic beta cells recapitulates neonatal diabetes

AUTHOR CONTACT:
Frances M. Ashcroft
University of Oxford, Oxford, United Kingdom.

View the PDF of this article at: https://www.the-jci.org/article.php?id=35772

Source: Karen Honey
Journal of Clinical Investigation

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