Effects of in vivo hexarelin treatment on pulsatile growth hormone secretion in streptozotocin-induced diabetic rats — ASN Events

Effects of in vivo hexarelin treatment on pulsatile growth hormone secretion in streptozotocin-induced diabetic rats (#311)

Xinli Zhang 1 , Yan Zhao 1 , Walter Thomas 1 , Chen Chen 1
  1. University of Queensland, St.Lucia, QLD, Australia

Growth hormone (GH) profile has been well characterized on Streptozotocin (STZ)-induced diabetic animal model. It was shown that there is a dramatically decline of GH secretion in STZ-induced diabetic animals. Hexarelin is a synthetic growth hormone secretagogue which is able to stimulate GH secretion. Thus we aim to investigate the effect of hexarelin on growth hormone secretion on STZ-induced diabetic animal model.
Male Wistar rats at age of 6-week old were injected intra-peritoneally with a single dosage of 65mg/kg STZ to induce diabetes for 6 weeks. During 6 weeks disease development, blood glucose level (once a week), water consumption (daily) and body weight gain (twice a week) were monitored. After 4 weeks of disease development, a group of control and diabetic animals were receiving daily hexarelin (100g/kg) treatment for 2 weeks. We then assessed GH secretion in rats from all groups. In addition, circulating levels of free fatty acids (FFAs) and IGF-1 were assessed.
We observed a significant increase of blood glucose level and slow body weight gain through 6 weeks disease development in STZ-induced diabetic animals. Pulsatile GH secretion in diabetic animals was characterized by a significant decline in total (356±75.3 vs 1243±141ng/ml per 6h, p<0.001), pulsatile (192±24.6 vs 1053±136ng/ml per 6h, p<0.001), basal (19.2±9.67 vs 213±41.9ng/ml per 6h, p<0.001) and the mass of GH secreted per burst (118±23.0 vs 355±39.9ng/ml, p<0.001) compared to control. In addition, impaired GH secretion followed an increase in circulating level of FFAs correlated to fat tissue but a decrease in circulating level of IGF-1 in diabetic rats. After hexarelin treatment, blood glucose level was gradually decreased in diabetic animals; body weight gain was increased in both control and diabetic group. Pulsatile GH secretion in diabetic group was characterized by a significant increase in total (826±197 vs 356±75.3ng/ml per 6h, p<0.05), pulsatile (524±44.6 vs 192±24.6ng/ml per 6h, p<0.001), basal (159±36.6 vs 19.2±9.67ng/ml per 6h, p<0.01) but not the mass of GH secreted per burst (178±28.9 vs 118±23.0ng/ml, p=0.14) compared to pre-treatment. In addition, diabetic animals showed dramatically decreased circulating level of FFAs correlated to fat tissue but suppression in circulating level of IGF-1.
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