Abstract
Significant growth hormone (GH) reductions have been reported in diabetic animal models with disturbed metabolic balance coinciding with GH deficiency. Therefore, enhanced GH secretion may have beneficial effects in controlling diabetes. Thus, we aim to investigate the effect of hexarelin, a synthetic GH secretagogue (GHS), on GH secretion in streptozotocin (STZ, 65 mg/kg)-induced diabetic rats. Daily hexarelin (100 μg/kg) treatment was performed for two weeks in four-week-long STZ-diabetic and vehicle control rats. Pulsatile GH secretion in STZ-rats was significantly reduced in total, pulsatile, basal, and mass of GH secretion per burst. In addition, impaired GH secretion was followed by an increase in fasting-level free fatty acids (FFAs) and a decrease in insulin-like growth factor 1 (IGF-1) compared to control rats. After hexarelin treatment, pulsatile GH secretion in STZ-rats was significantly increased in total, pulsatile, and basal, but not in the mass GH secretion per burst, compared to STZ-rats without hexarelin treatment. However, there was no significant elevation in GH secretion in the hexarelin-treated control group. In addition, hexarelin-treated STZ-rats showed a significant decrease in fasting level FFAs, whereas suppression of fasting level for IGF-1 was maintained. These results suggest that STZ-induced diabetic rats have impaired pulsatile GH secretion, causing increased FFAs and decreased IGF-1 levels in circulation. Hexarelin injections for two weeks is able to normalize impaired pulsatile GH secretion with normal fasting levels of FFAs, but fails to recover IGF-1 levels.
Highlights
Growth hormone (GH) is synthesized, stored, and secreted by somatotrophs in the anterior pituitary gland
Hypothalamic growth hormone-releasing hormone (GHRH) is a major regulator of GH secretion, which stimulates pituitary GH release; whereas somatotropin-releasing inhibiting factor (SRIF) or somatostatin neurons plays an inhibitory effect on pituitary GH release [1,2]
Insulin-like growth factor 1 (IGF-1) release is predominantly regulated by GH in various tissues, in the liver because more than 50% of circulating IGF-1 is originally secreted from hepatic tissue [3]
Summary
Growth hormone (GH) is synthesized, stored, and secreted by somatotrophs in the anterior pituitary gland. Experimental diabetes studies showed that insulin deficiency resulted in decreased expression of GH receptors, which was restored by insulin treatment with normalized level of IGF-1 [16]. Increased GH release was associated with elevated GHRH-R expression after long-term Hex treatment, suggesting that GHSs may stimulate GH secretion through the action of GHRH [24]. Both in vivo and in vitro investigations demonstrated that arcuate nucleus (ARC) c-fos expression was increased by the GHS-stimulating effect, as GHS-R expression was present in ARC GHRH neurons [25,26,27]. The beneficial effects of this increase in GH will be studied
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