Untersuchungen zur genetischen Grundlage des metabolischen Phänotyps von Nachkommen hyperglykämischer Elterntiere im Mausmodell

Gertsen, Mila GND

Numerous epidemiologic studies have shown that adverse intrauterine environment such as maternal diabetes or obesity during pregnancy can induce metabolic disorder in offspring which is associated with insulin resistance, impaired glucose tolerance and even type II diabetes. In this study we tested the hypothesis on a mouse model with hypoinsulemic autosomal dominant diabetes if maternal or paternal hyperglycemia and the modified maternal diet will change the wild type offspring┬┤s metabolic phenotype and arginin-NO-metabolism. Furthermore, we took a closer look at how epigenetic changes, in particular altered DNA methylation in the NO-metabolic active genes, effect the offspring phenotypes. The mouse model with offspring of hyperglycemic female and male mice and modified maternal high sucrose diet have been chosen to represent the common metabolic conditions and nutrition habits in humans during pregnancy. Both maternal/paternal diabetes and maternal high sucrose diet modification led to gender-specific changes in wild type offspring such as weight, blood glucose level, NO-metabolite and altered gene expression of some NO-metabolizing genes. Our DNA methylation analysis of CpG islands in nNOS gene of skeletal muscle has shown no changes between methylation status in offspring with maternal hyperglycemia, though. The changes of methylation in nNOS gene of skeletal muscle seem not to be a molecular cause for changes in NO-arginin metabolism, as we have learned.

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Gertsen, Mila: Untersuchungen zur genetischen Grundlage des metabolischen Phänotyps von Nachkommen hyperglykämischer Elterntiere im Mausmodell. 2019.

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