Developmental programming of type 2 diabetes during diabetic pregnancy: Involvement of hyperglycemia-induced inflammation during fetal development
Zusammenfassung der Projektergebnisse
In conclusion, during my fellowship I was able to show that: • Maternal hyperglycemia during pregnancy is associated with type 2 diabetes in their offspring. • Offspring of diabetic mothers showed hyperglycemia already on day one of life suggesting that they are exposed to higher glucose levels during pregnancy. • Programming of type 2 diabetes was not connected to low or high birth weights. Additionally, we did not saw "catch-up" growth or growth retardation. • Offspring of Ins2Akita mice showed a clearly abnonnal glucose homeostasis by possessing elevated fed and fasted blood glucose levels and displaying a significant less insulin-responsiveness. • Pancreas development and morphology in offspring of diabetic mothers was clearly altered shown in lower pancreas wet weights, abnormal morphology and organization of islets and α- and ß-cells suggesting an eariy imprinting of beta cell dysfunction in offspring of diabetic mottiers. • Pro-inflammatory cytokines, which are down stream genes of NFKB, are involved in diabietic programming. • Tissues of offspring of diabefic mothers are "inflamed" during pregnancy respectively postnatal leading to type 2 diabetes later on. • Gender-speciflc pro-inflammatory patterns in offspring of diabetic mothers were found. In summary, it was possible to increase evidence that maternal hyperglycemia during pregnancy causes pro-inflammatory response in tissues of their offspring leading to type 2 diabetes later on. Knowledge, methods and techniques will be transferred to the Ludwig Maximilians-University in Munich.
