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Severe Maternal Hyperglycemia Exacerbates the Development of Insulin Resistance and Fatty Liver in the Offspring on High Fat Diet

DOI: 10.1155/2012/254976

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Background. Adverse maternal environments may predispose the offspring to metabolic syndrome in adulthoods, but the underlying mechanism has not been fully understood. Methods. Maternal hyperglycemia was induced by streptozotocin (STZ) injection while control (CON) rats received citrate buffer. Litters were adjusted to eight pups per dam and then weaned to standard diet. Since 13 weeks old, a subset of offspring from STZ and CON dams were switched to high fat diet (HFD) for another 13 weeks. Glucose and insulin tolerance tests (GTT and ITT) and insulin secretion assay were performed; serum levels of lipids and leptin were measured. Hepatic fat accumulation and islet area were evaluated through haematoxylin and eosin staining. Results. STZ offspring exhibited lower survival rate, lower birth weights, and growth inhibition which persisted throughout the study. STZ offspring on HFD showed more severe impairment in GTT and ITT, and more profound hepatic steatosis and more severe hyperlipidemia compared with CON-HFD rats. Conclusions. Offspring from diabetic dams would be prone to exhibit low birth weight and postnatal growth inhibition, but could maintain normal glucose tolerance and insulin sensitivity. HFD accelerates development of insulin resistance in the offspring of diabetic dams mainly via a compensatory response of islets. 1. Introduction Metabolic syndrome (MetS) is a clustering of metabolic disorders including hyperglycemia, hypertension, dyslipidemia, overweight, and central obesity, with insulin resistance as the central feature of this syndrome [1]. A global increase in the prevalence of MetS has been found in the last decades due to the worldwide epidemic of obesity [2, 3]. The risk of the MetS depends on genetic susceptibility but is modulated by pre- and postnatal environmental factors. A growing body of evidence suggests that adverse environmental conditions during crucial periods of development may predispose individuals to develop different components of the MetS in adulthood [4]. Of particular note is maternal diabetes, including type 1 and type 2 diabetes and gestational diabetes mellitus (GDM). An overall increasing prevalence of diabetes indicates an emergence of diabetes among childbearing women. During pregnancy, especially during critical window periods for organogenesis and fetal development, unsatisfactory glycemic control is known to increase the incidence of severe obstetrical complications, including preeclampsia, macrosomia, and Caesarean section. Additionally, intrauterine exposure to a hyperglycemic environment predisposes


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