Maternal diabetes can induce permanent changes in glucose homeostasis that can occur pre- and post-natal and leads to type 2 diabetes in adulthood. This study aimed to investigate the effect of maternal diabetes on the F1 offspring peripheral glucose sensing and mitochondrial biogenesis in an attempt to clarify the mechanism of diabetogenic programming. Two groups of female Wistar rats were used (diabetic and control); diabetes was neonatally induced by STZ injection to 5-day old rats. After the pregnancy and delivery, the offspring were weaned to control diet or high-caloric (HCD) diet and followed up for 30 weeks. Every 5 weeks, OGTT was constructed, and serum and tissues were obtained for the assessment of mTFA, mtDNA, UCP2, insulin receptor (IR), phospho-insulin receptor (phospho-IR), and GLUT4. The result indicated impaired glucose tolerance (IGT) and insulin resistance in the offspring under control diet at the 15th week of age and thereafter while those offspring under HCD showed IGT at 10th week, and diabetes was evidenced at the 25th week of age. This defect in glucose metabolism was preceded by impairment in the phosphorylation of IR and decreased IR and Glut4 that cause impaired glucose sensing together with inhibited mitochondrial biogenesis in muscle and adipose tissues. This study indicated that maternal diabetes caused impaired glucose sensing and insulin resistance in the peripheral tissues and caused change in the expression of genes involved in mitochondrial biogenesis and function. Post-natal feeding with HCD may accelerate these changes. Male F1 offspring appears to be more sensitive than females for fetal programming of T2D.

Background: The oxidative stress and disturbed redox signaling during gestation my play an important role in the fetal programming of adult diabetes. Objective: The study aimed to investigate the effects of maternal diabetes on pre-and post-natal pancreatic and peripheral tissues redox and oxidative status in order to clarify their role in the diabetogenic programming of F1 offspring. Methods: Two groups of female Wistar rats were used (diabetic and control); diabetes was neonatally induced by STZ injection to 5-day old rats. 10 pregnancies of each group were terminated at GD 17 to obtain placentas and fetal pancreas, liver, muscle and adipose tissues for prenatal measurements. The rest of pregnancies were completed to term and the offspring were weaned to control diet or high-caloric (HCD) diet and followed up for 30 weeks. Every 5 weeks 10 male rats were sacrificed and serum and tissues were obtained for assessment of fasting blood glucose, tissues content of 8-oxo-dG, TBARS, GSH, GSSG, antioxidant enzymes and caspase-3. Results: The results indicated that, prenatally redox status of the foetuses of diabetic mothers is shifted toward more oxidizing environment which results from elevated oxidative stress and impaired antioxidants as indicated by elevated fetal tissues content of 8-oxo-dG, TBARS and GSSG and decreased GSH and GSH/GSSG ratio. All of these induce the apoptotic pathway in fetal pancreas. Postnatally, impaired glucose tolerance in the offspring of diabetic mothers is detected at 15 th week of age and no hyperglycemia was detected until age of 30 weeks in the offspring under CD while some of offspring under HCD at age 25 weeks and most of them at 30 weeks have developed hyperglycemia. The pancreas of the offspring of diabetic mothers suffers from oxidative stress from the 5 th week of age as indicated by elevated levels of nuclear and mitochondrial 8-oxo-dG contents and TBARS. Also, GSH level showed depletion with age and the activity of glutathione reductase was lower in the β-cell and hepatic tissues of the offspring of diabetic mothers. The prenatal shift of redox status persists postnatal and exaggerates with age which may explain the significant induction of the apoptotic pathway in the pancreatic β-cell. Conclusion: Maternal diabetes can crucially affect the redox status in fetal tissues prenatally and these effects can persist postnatal which may play an important role in the programming of the metabolic state of the offspring. Postnatal diet play im-M. A. Kamel et al. 112 portant role in accelerating development of metabolic derangements and aggravates oxidative stress in the tissues of F1 offspring.

Background: Maternal diabetes is one of the fundamental intrauterine disturbances that have direct and long lasting consequences on the health of the offspring. The risk for an individual to develop various vascular diseases throughout life is hypothesized to be related to diabetic gestation.Aim: The present study aimed to evaluate the postnatal levels of different independent risk factors for vascular diseases including homocysteine (Hcy), nitric oxide (NO), lipid profile, glucose homeostasis and insulin resistance in the rat offspring of diabetic mothers. The effect of postnatal feeding with high caloric diet (HCD) was also assessed.Methods: Two groups of female Wistar rats were used (diabetic and control); diabetes was neonatally induced by STZ injection to 5-day old rats. Pregnancy was induced by mating control or diabetic females with normal healthy males overnight and the pregnancies were completed to term. After delivery the offspring were weaned to control diet (CD) or high-caloric diet (HCD) (Table 1) and followed up for 30 weeks. So the offspring groups were as following: F1 offspring of control mothers under control diet (CF1-CD), F1 offspring of control mothers under HCD (CF1-HCD), F1 offspring of diabetic mothers under control diet (DF1-CD) and F1 offspring of diabetic mothers under HCD (DF1-HCD). Every 5 weeks 0.5 ml blood samples were obtained from the 20 male and female rats for assessment of fasting blood glucose, insulin, triglycerides, cholesterol (total, HDL-C and LDL-C), homocysteine and nitric oxide end products (NOx).Results: The results indicated that maternal diabetes caused an age-dependent alteration in glucose homeostasis and resulted in insulin resistance especially in male offspring. Also, lipid profile showed Am. J. Biomed. Sci. 2014, 6(3), 201-216; doi: 10.5099/aj140300201 © 2014 by NWPII. All rights reserved 202 elevation of triglycerides, cholesterol and LDL-C while HDL-C showed significant decline in the offspring of diabetic mothers. These disturbances in glucose and lipid metabolism were associated with elevated plasma level of Hcy from 25 week age and thereafter. Also, there was an elevation in the level of nitric oxide end products (NOx).Conclusion: Maternal diabetes cause increased risk for vascular diseases in the offspring. The mechanisms of this predisposition involve disturbed lipid profile, insulin resistance, increased circulatory levels of Hcy (independent risk factor for vascular diseases) and nitric oxide end products. Male rat offspring appear to be more sensitive for the development of vascular diseases than female offspring and postnatal diet plays important role in this predisposition as the risk increases with high caloric diet.