释 义 西格列汀（糖尿病类治疗药物名称）
例 句 Conclusion The sitagliptin can improve the insulin resistance situation in type 2 diabetes patients. 结论西格列汀可改善2型糖尿病患者胰岛素抵抗水平。
作者： Jessica K Devin
期刊：J Clin Endocrinol Metab
Growth hormone (GH) is secreted in a pulsatile fashion from the pituitary gland and exerts its effects either directly, via activation of the GH receptor, or indirectly, through hepatic insulin-like growth factor-1 (IGF-1). In adults, GH has important effects on the vasculature and body composition. GH increases endothelium-dependent vasodilator function and reduces inflammation. We have previously shown that patients with low GH have impaired conduit artery vasodilator function along with decreased tissue-type plasminogen activator (tPA) activity and a defective fibrinolytic response to venous occlusion. Others have corroborated these findings and further demonstrated that these vascular indices improve with GH replacement therapy. GH also has anabolic and lipolytic effects. Conversely, GH secretion is reduced in obesity and particularly in individuals with visceral adiposity. Women with increased visceral adipose tissue (VAT) demonstrate a four-fold reduction in mean GH levels as compared to those without. Normalization of GH secretion in patients with diminished GH affords one potential mechanism to address simultaneously both VAT and cardiovascular risk. Unfortunately, therapy with recombinant GH does not restore pulsatile secretion, is not subject to physiologic negative feedback by IGF-1, and is limited by hyperglycemia. We propose that an alternative strategy to enhance endogenous GH secretion in humans is to inhibit the degradation of endogenous GH releasing hormone (GHRH) by the dipeptidyl peptidase-4 (DPP4) enzyme. GHRH is the primary stimulus for pituitary GH secretion and determines GH pulsatility. Endogenous GHRH has a half-life of six minutes as it is degraded and inactivated by DPP4. Sitagliptin was the first oral DPP4 inhibitor approved by the US Food and Drug Administration for the management of hyperglycemia in patients with type 2 diabetes mellitus. Sitagliptin improves post-prandial hyperglycemia in a glucose-dependent manner by decreasing the degradation of the incretin hormone, glucagon-like peptide-1 (GLP1), and can therefore be safely given to patients without diabetes mellitus. We recently found that acute DPP4 inhibition with sitagliptin enhances stimulated GH secretion and free IGF-1 levels in healthy, lean women. Moreover, while vasodilation and tPA activity levels increased in both men and women during stimulated GH secretion, women demonstrated an enhanced vascular response to increased GH. The effect of chronic DPP4 inhibition on pulsatile GH secretion in individuals with low GH levels has not been studied.