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Pregnancy in human IAPP transgenic mice recapitulates beta cell stress in type 2 diabetes – published online 09/03/2019

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Tatyana Gurlo, Sarah Kim, Alexandra E. Butler, Chang Liu, Lina Pei, Madeline Rosenberger, Peter C. Butler

Gestational diabetes is a risk factor for subsequent type 2 diabetes. As the availability of human pancreas tissue in pregnancy is limited, little is known about the islet changes in women vulnerable to type 2 diabetes, either during or after pregnancy. Moreover, most rodent models of type 2 diabetes do not develop gestational diabetes. This may be because, in humans, beta cell failure in type 2 diabetes is characterised by protein misfolding toxicity mediated by islet amyloid polypeptide (IAPP) but rodent IAPP does not form toxic oligomers. In this issue, Gurlo et al ( investigated whether mice transgenic for human IAPP develop pregnancy-related diabetes. The transgenic mice showed beta cell stress that mimicked the endoplasmic reticulum stress, oxidative damage and attenuated autophagy observed in beta cells in type 2 diabetes. Moreover, this beta cell damage persisted after pregnancy, leading to subsequent diabetes before or during a second pregnancy, with further exacerbation of beta cell stress during the second pregnancy. The authors conclude that this model offers accessible islet tissue to investigate strategies to mitigate beta cell stress during pregnancy, as well as an opportunity to investigate the effects of gestational diabetes on fetal development.

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