Maher Abd El-Naby Kamel
The intra-uterine milieu programs the health of an individual throughout life. This effect has been called fetal origin of adult disease. The altered maternal metabolism is associated with a diabetogenic effect in the adult offspring. The pancreatic glucose-stimulated insulin secretion (GSIS) and peripheral response to insulin are central in glucose homeostasis in fetal circulation and the modulation of these processes during the fetal development may have a serious complications long-lasting. This study was aimed to delineate the prenatal (at gestational day 17) effects of different maternal health challenges on the fetal glucose sensing mechanisms including GLUT2, glucokinase, mitochondrial transcription factor A (mTFA), uncoupling protein 2 (UCP2), phospho-insulin receptor (Phosho-IR) and glucose transporter 4 (GLUT4). We used hyperglycemic, obese and malnourished beside normal female rats to establish pregnancy that was terminated at GD 17. The fetal pancreas, liver, muscle and adipose tissues were obtained for determination of the studied parameters. The results indicated up-regulation of GLUT2, glucokinase, mtTFA and UCP2 expression in fetal pancreas and liver of hyperglycemic mothers fetuses while maternal obesity mildly up-regulate expression of GLUT2, glucokinase and UCP2 in fetal pancreas, liver and adipose tissues, while malnutrition causes down-regulation of UCP2 in pancreas, it up-regulates GLUT2 and glucokinase in liver. In muscle and adipose tissues the level of phosho-IR was increased under maternal hyperglycemia and malnutrition while GLUT4 level increased under maternal diabetes only.
We can conclude that the fetal adverse environments can prenatally affect the expression of genes that linked to the development of type 2 diabetes including genes controlling glucose sensing and metabolism.
