Effects of insulin - like growth factor binding protein-3 (IGFBP-3) on diabetes - induced erectile dysfunction (ED)

胰岛素样生长因子结合蛋白 3 (IGFBP-3) 对糖尿病引起的勃起功能障碍 (ED) 的影响

• 批准号: 13671665
• 负责人: SOU Jintetsu
• 金额: $ 2.3万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671665/
• 关键词: IGF-I; IGFBP-3; Erectile Dysfunction (ED); IGFBP-1

Diabetes-induced erectile dysfunction (ED) is assumed to be of a neurovascular basis. In diabetic rats, several physiological pathways leading to erection in the penis have been reported to be impaired. However, the cntire picture of the molecular mechanisms underlying ED remains to be clarified. To overview the possible axes involved in ED under diabetes, we carried out broad-scale gene expression profiling in the crura penis of streptozotocin-induced disbetic rats. Eight weeks after induction of hyperglycemia by intraperitoneal injection of streptozocin (60mg/kg), total RNA was isolated from the cura penis of male Wister rats by the acid guanidinium-phenol-chloroform method. ^<32>P-labeled cDNAs were synthesized from RNA obtained from diabetic and age-matched control animals and hybridized separately to the cDNA expression arrays. Relative expression levels of the genes on each array were quantitatively determined and comparedAmong the 588 genes on the array investigated, expression level of insulin-like growth factor binding protein 3 precursor (IGFBP-3) was highly upregulated in diabetic group. On the other hand, expression levels of ErbB3 EGF receptor-related proto-oncogene, G1/S-specific cyclin D2, liver carboxylesterase 10 precursor, and UDP-galactose-ceramide galactosyltransferase were markedly decreasedThe augmented expression of IGFBP-3 under hyperglycemia may elicit reduced bioavailability of IGF in the corpus cavernosum. As IGF is known to induce NO-mediated vascular relaxation as well as to regulate cell cycle progression, the present findings may lead to a new avenue of treatment modality for ED in diabetic patients

糖尿病引起的勃起功能障碍（艾德）被认为是神经血管基础。在糖尿病大鼠中，据报道导致阴茎勃起的几种生理途径受损。然而，艾德的分子机制的全貌仍有待澄清。为了研究糖尿病艾德性勃起的可能调控机制，我们对链脲佐菌素诱导的糖尿病大鼠阴茎脚进行了广泛的基因表达谱分析。腹腔注射链脲佐菌素（60 mg/kg）诱导大鼠高血糖8周后，用酸性胍-酚-氯仿法从雄性Wister大鼠阴茎毛中提取总RNA。从<32>糖尿病动物和年龄匹配的对照动物获得的RNA合成13 P标记的cDNA，并分别与cDNA表达阵列杂交。在芯片上检测的588个基因中，胰岛素样生长因子结合蛋白3前体（IGFBP-3）的表达水平在糖尿病组显著上调。另一方面，ErbB 3 EGF受体相关原癌基因、G1/S特异性细胞周期蛋白D2、肝羧酸酯酶10前体和UDP-半乳糖-神经酰胺半乳糖基转移酶的表达水平显著降低。由于已知IGF诱导NO介导的血管舒张以及调节细胞周期进程，本研究结果可能导致糖尿病患者艾德治疗模式的新途径