Impaired peripheral glucose sensing in F1 offspring of diabetic pregnancy

Abstract

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.

n-3 Polyunsaturated Fatty Acids Decrease Long-Term Diabetic Risk of Offspring of Gestational Diabetes Rats by Postponing Shortening of Hepatic Telomeres and Modulating Liver Metabolism

“…In Ding’s study, GTT was impaired in 8-weeks-old offspring mice [27]. Kamel et al found impaired GTT in offspring rats at 15 weeks of age [28]. Population studies found that the diabetic risk in GDM offspring was increased at childhood, puberty, and adulthood [29,30,31].…”

Maternal chromium restriction induces insulin resistance in adult mice offspring through miRNA

“…Catch-up growth following intrauterine growth restriction reduces the expression of the PI3K p110β subunit at 22 days old, and Akt phosphorylation and Akt-2 protein levels at 3 months in adipose tissue ( 48 ). In addition, maternal diabetes has been revealed to decrease GLUT4 in the adipose and muscle tissues of 10-week-old male offspring ( 49 ).…”

In Utero Nutritional Manipulation Provokes Dysregulated Adipocytokines Production in F1 Offspring in Rats

“…Therefore, the offspring groups were as follows: F1 offspring of control mothers under CD (CF1-CD), F1 offspring of control mothers under HCD (CF1-HCD), F1 offspring of obese mothers under CD (OF1-CD), F1 offspring of obese mothers under HCD (OF1-HCD), F1 offspring of malnourished mothers under CD (MF1-CD), and F1 offspring of malnourished mothers under HCD (MF1-HCD). Pregnancy outcome and composition of diets used were previously published [ 12 ]. Every 5 weeks postnatally, 10 pups of each subgroup were culled after overnight fasting to obtain blood samples for biochemical analysis.…”