Green Brian D, Irwin Nigel, Cassidy Roslyn S, Gault Victor A, Flatt Peter R
School of Biomedical Sciences, University of Ulster, Coleraine, BT52 1SA, Northern Ireland, United Kingdom.
Peptides. 2006 Sep;27(9):2343-9. doi: 10.1016/j.peptides.2006.04.008. Epub 2006 May 24.
Pituitary adenylate cyclase-activating peptide (PACAP) is a ubiquitous peptide of the glucagon superfamily that is involved in glucose homeostasis and regulation of insulin secretion. This study employed the PACAP receptor antagonist, PACAP(6-27) to evaluate the role of endogenous PACAP in genetic obesity-related diabetes and related metabolic abnormalities using ob/ob mice. Acute in vivo antagonistic potency of PACAP(6-27) was confirmed in ob/ob mice by blockade of the insulin-releasing action but not hyperglycaemia. In longer-term studies, ob/ob mice were given once daily injections of PACAP(6-27) or vehicle for 14 days. Feeding activity, body weight, basal plasma glucose and plasma insulin concentrations were not significantly affected by chronic PACAP(6-27) treatment. However, PACAP(6-27) treatment impaired glucose tolerance, insulin sensitivity and the glycaemic response to feeding. Plasma glucagon and lipids were unchanged. These observations indicate a role of endogenous PACAP for normal glucose homeostasis, but indicate a minor involvement in the regulation of insulin secretion in ob/ob mice.
垂体腺苷酸环化酶激活肽（PACAP）是一种广泛存在于胰高血糖素超家族中的肽，参与葡萄糖稳态和胰岛素分泌的调节。本研究使用PACAP受体拮抗剂PACAP(6 - 27)，以ob/ob小鼠为模型评估内源性PACAP在遗传性肥胖相关糖尿病及相关代谢异常中的作用。通过阻断胰岛素释放作用而非高血糖，证实了PACAP(6 - 27)在ob/ob小鼠体内的急性拮抗效力。在长期研究中，给ob/ob小鼠每日注射一次PACAP(6 - 27)或赋形剂，持续14天。慢性PACAP(6 - 27)治疗对摄食活动、体重、基础血糖和血浆胰岛素浓度无显著影响。然而，PACAP(6 - 27)治疗损害了葡萄糖耐量、胰岛素敏感性以及对进食的血糖反应。血浆胰高血糖素和脂质未发生变化。这些观察结果表明内源性PACAP对正常葡萄糖稳态起作用，但提示其在ob/ob小鼠胰岛素分泌调节中的作用较小。
