Adverse effects of perinatal protein restriction on glucose homeostasis in offspring of Sprague-Dawley rats

Abstract

Adequate evidence suggests that poor in-utero environment produced by early life dietary disturbance may predispose offspring to chronic diseases in adult life. It remains to be defined the adverse effect of early exposure due to perinatal protein restriction (PPR) (gestation, lactation and/or both) on the regulators of glucose homeostasis of the male offspring in later life. Hence, the present study investigated the role of perinatal protein restriction on the regulators of glucose homeostasis in adult offspring. Twenty-four pregnant and twelve male Sprague-Dawley rats were used. They were fed either a normal diet containing 20% protein or protein-restricted (PR) diet with 8% protein. The dams were given PR diet up to parturition (in-utero group, IUPR), or from birth to postnatal day 21 (lactation group, LPR) or for a period covering both groups (combined group, CPR). Control dams with control diet was run in parallel for comparison. At day 120, oral glucose tolerance, insulin tolerance, fasting blood glucose, fasting insulin level were determined. Hepatic and myocytic glycogen contents, GLUT-4 protein abundance, alpha amylase and alpha glucosidase activities were also assessed. The results revealed that glucose tolerance was unchanged, insulin sensitivity was significantly decreased in IUPR and CPR offspring. HOMA-IR elicited a significant elevation (p<0.01) in IUPR and CPR offspring compared with CONT. Hepatic and myocytic glycogen contents in all PPR offspring significantly decreased compared with CONT. GLUT-4 protein was significantly (p<0.01) reduced in all PPR offspring compared with CONT. Alpha amylase activity decreased significantly (p<0.01) in IUPR and CPR offspring with a significant increase (p<0.01) in LPR offspring compared with CONT. However, alpha glucosidase activity showed no significant difference (p>0.01) in all PPR offspring compared with CONT. In conclusion, the data described in the present investigation provides ample evidence that PPR remarkably malprogram the offspring to impairment of glucose homeostasis with blunted insulin action in the tissues of the periphery which eventually reduces uptake of glucose, utilization and absorption as well as deposition of glycogen in liver and skeletal muscle leading to insulin resistance in PPR offspring.