腎と骨代謝 Vol.19 No.1(1-3)


特集名 糖尿病と骨・カルシウム代謝異常
題名 発症機序 (3) Advanced glycation end-products (AGEs)
発刊年月 2006年 01月
著者 山本 威久 箕面市立病院小児科
【 要旨 】 糖尿病および糖尿病による末期腎不全患者で認められる無形成骨の病因における糖化最終産物 (AGEs) の役割について,ヒト由来の初代培養骨芽細胞および副甲状腺細胞を用いた知見を示した.AGEs受容体の一つであるRAGEはヒト骨芽細胞および副甲状腺組織に存在し,AGEsは骨芽細胞の骨形成能を抑制するのみならず,低カルシウム刺激に対する副甲状腺細胞からの副甲状腺ホルモン (PTH) 分泌を抑制した.このPTH分泌抑制機序には,AGEsによる時間依存性の細胞内カルシウム濃度上昇効果が関与するものと考えられた.以上の知見から,AGEsは,糖尿病および糖尿病による末期不全患者で認められる無形成骨の病因の一つであると考えられる.
Theme Impaired metabolism of bone and calcium in diabetes mellitus
Title Role of AGEs in pathogenesis of adynamic bone diseases in diabetes mellitus
Author Takehisa Yamamoto Department of Pediatrics, Minoh City Hospital
[ Summary ] In patients with diabetes mellitus (DM) and end stage renal failure (ERF) with complications of DM, adynamic bone disease was often reported on from the basis of bone biopsy investigations. Serum levels of advanced glycation end-products (AGEs) were reported to be elevated. In this review, we showed the effects of AGEs on primary human osteoblasts and parathyroid cells in culture. AGEs were made by incubating bovine serum albumin with glucose 6 phosphate for 8 weeks. AGEs-BSA (1,000 μg / ml) levels showed an inhibitory effect on human osteoblasts in terms of the production of procolagen c propeptides and osteocalcin, which were regarded as bone forming parameters. On the other hand, the same concentration of AGEs-BSA inhibited the increase of parathyroid hormone secretion from the cultured human parathyroid cells induced by low calcium medium concentrations. Also, AGEs-BSA increased time dependently in relation to intracellular calcium levels in HEK 293 cells, expressing wild type human calcium-sensing receptors. These data suggested the important role of AGEs in the pathogenesis of adynamic bone disease in DM and ERF patients with DM complications.
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