While it appears that obesity is associated with the higher incidence of type 2 diabetes mellitus (T2DM), recent findings that T2DM affects non-obese people are becoming more noticeable. Many of those who are not obese by traditional weight measurements have an increased percentage of body fat distributed predominately in the abdominal and visceral regions. Disorders of lipid metabolism play a major role in the pathogenesis of this nonobese diabetic phenotype. For examples, lipodystrophic patients develop insulin resistance due to insufficient adipose tissue and aged lean people with diabetes have defects in mitochondrial lipid oxidative mechanisms. Such non-obese diabetic patients are at increased risk of developing cardiovascular (CVD) complications. The management of non-obese T2DM should focus not only on life style modifications or blood glucose control but also strategies for correction of lipid metabolic aberrations. Growth hormone (GH) exerts powerful influences on growth and body composition. In obese animal models and human, GH is known to correlate inversely with insulin concentrations. Some studies suggest that insulin may have a direct inhibitory effect on GH secretion, whereas others showed that insulin inhibits GH secretion via suppression of growth hormone releasing hormone (GHRH) or stimulation of somatostatin (SST). Although GH-insulin relationship is well documented in obesity, studies of this GH-insulin relationship in non-obese diabetes are sparse and contradictory. Thus, this study aimed to investigate the pulsatile GH profile and its regulatory factors in MKR mice which are non-obese diabetic mice generated by igf-1 receptor mutation in skeletal muscle. Our observations demonstrated that unlike obese mice, MKR mice had normal to higher pulsatile GH secretion at different age groups. Nevertheless, there were no detectable changes in gene expressions of hypothalamic GHRH and SST. Interestingly, hypothalamic orexigenic NPY gene expression was increased that might affect GH secretion. These findings suggest that the relationship between GH and insulin was altered in MKR mice, leading to higher GH concentrations despite hyperinsulinaemia. Given that MKR mice exhibited postnatal growth retardation, we anticipated that endogenous GH levels would increase to facilitate rapid linear growth and promote muscle development that assist nutrient uptake and utilization.Therapy using growth hormone secretagogues (GHS) that increase endogenous GH secretion through binding to the ghrelin receptor (GHS-R1a) might have beneficial effects on lipid metabolism with less adverse effects on glucose metabolism than exogenous GH administration. Recent studies have provided some interesting avenues for further exploration on how Hexarelin, one of synthetic peptide GHS, enhanced fat metabolism of white adipose tissue (WAT) via CD36 activation independently of GHS-R1a. To address the effects of Hexarelin in non-obese diabetes, MKR were received daily intraperitoneal (I.P.) injection of Hexarelin (200ug/kg body ...
