Early postnatal exposure to stress may predispose neonates to certain disorders including glucose metabolism defects in later life. Pancreas is an immature organ at birth and HB9 as a transcription factor (which is expressed in adulthood only in pancreatic beta cells) plays a role in the final development and differentiation of pancreatic beta cells. Also, studies have shown that stress could alter the expression of transcription factors. This study investigated the effect of early life stress on the expression of pancreatic HB9 protein and insulin secretion from isolated islets in young adult male Wistar rats subjected to chronic stress. Male pups from different litters were randomly allocated into four different groups (n=8/group). The study groups consisted of the Control (only placed inside the communication box with no application of foot shock stress at either level of age); Early STR (placed inside the communication box at both age levels, but received stress only in early life); Young adult STR (placed inside the communication box at both age levels, but received stress only in young adulthood); and Early+ Young adult STR (received stress in both early life and young adulthood). Foot shock stress was induced twice daily for 5 consecutive days by a communication box at two levels of age: early life at 2 weeks of age (0.5 mA, 1 Hz, lasting 10 s, every 60 s for 30 min); young adulthood at 8–10 weeks of age (1 mA, 1 Hz, for 10 s every 60 s for 60 min). Blood samples were taken immediately after the first and the last stress exposure to determine plasma corticosterone levels in young adult rats. Moreover, after the last exposure to stress, isolated islets’ insulin secretion, and pancreatic amounts of HB9 protein were measured. One- and Two-Way ANOVA were used for statistical analysis. The results showed that although plasma corticosterone level was lower in Early STR group than the Control group, it was markedly higher in Early+Young adult STR group immediately after exposure to stress, than the Control and Early STR groups. The amount of HB9 protein level was significantly lower in Early STR and Early+Young adult STR groups than the Control and Young adult STR groups respectively. However, it showed an increment in Early+ Young adult STR group compared to the Early STR group. The insulin output from pancreatic isolated islets, in response to basal glucose concentration (5.6 mM), was lower in Early STR group than the Control and Early+Young adult STR groups, whereas in response to high glucose concentration (16.7 mM) showed a higher value than its respective Control group. In the Early+Young adult STR group the insulin output showed a higher value in response to 16.7 mM glucose concentration, but no difference in response to 5.6 mM glucose, compared to the Control and young adult STR groups. Early life stress could alter hypothalamic-pituitary-adrenal axis activity in adulthood and therefore may affect plasma corticosterone level and HB9 protein expression level in the presence or absence of adulthood stress. Moreover, early life stress possibly by decreasing HB9 protein levels decreases insulin secretion ability of the isolated islets in response to basal glucose level and makes the organism susceptible to impaired glucose metabolism in adulthood.

Early life stress effects on pancreatic HB9 expression and insulin secretion in chronically stressed young adult rats