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

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 13671665
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: SOU Jintetsu Urology, Kyoto Pref. Univ. of Med. Assistant Professor, 医学部, 助手 (40305587)
• Co-Investigator(Kenkyū-buntansha): NAKAMURA Naoto Intermal Medicine, Kyoto Pref. Univ. of MED. Assistant Professor, 医学部, 講師 (40227921) ; KATSUYAMA Masato Pharmacology, Kyoto Pref. Univ. of MED. Assistant Professor, 医学部, 助手 (60315934) ; YABE Chihiro (NISHIMURA Chihiro) Pharmacology, Kyoto Pref. Univ. of MED. Professor, 医学部, 教授 (70150571) ; KAWAUCHI Akihiro Urology, Kyoto Pref Univ. of Med. Assistant Professor, 医学部, 講師 (90240952) ; MIKI Tsuneharu Urology, Kyoto Pref Univ. of Med. Professor, 医学部, 教授 (10243239)
• Project Period (FY): 2001 – 2002
• Keywords: IGF-I / IGFBP-3 / Erectile Dysfunction (ED)

Research Abstract

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 compared
Among 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 decreased
The 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