Pancreatic β-cell dysfunction is major characteristic of diabetes and destructive β-cell morphology has been found in different diabetic animal models. Growth hormone secretagogue, ghrelin, was reported has protective effect on pancreatic β-cell function and able to normalize blood glucose level in diabetes. Thus, we aim to use synthetic growth hormone secretagogue, hexarelin, to investigate pancreatic β-cell function in streptozotocin (STZ)-induced diabetic animal model.
STZ-induced diabetic rat was employed as animal model in comparison with control vechile. 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. After 4 weeks of disease development, a group of control and diabetic animals were receiving daily hexarelin (100mg/kg) treatment for 2 weeks. During 6 weeks disease development, blood glucose level (once a week), water consumption (daily) and body weight gain (twice a week) were monitored. By the end of treatment, GTT, ITT, blood plasma insulin level and pancreatic islets immunostaining 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. After hexarelin treatment, body weight gain increased and blood glucose level decreased. Islets of control animals were round, with a clear boundary, normal structure and cell numbers. But in diabetes group, numbers of insulin-positive cells were sharply declined and structure of islets was disrupted. In the group co-treated with STZ and hexarelin, the numbers of insulin-positive cells increased significantly and showed close-to-normal structure of islets. Further measurement on insulin level under fasting and feeding condition showed that insulin level was significantly declined in diabetic animals but increased in both treated control and diabetic animals. There was not much difference in GTT study but hexarelin treated diabetic animals exhibited good insulin sensitivity in ITT study.