Transient increase in renal insulin-like growth factor binding proteins during initial kidney hypertrophy in experimental diabetes in rats
Transient increase in renal insulin-like growth factor binding proteins during initial kidney hypertrophy in experimental diabetes in rats
复制标题
实验性糖尿病大鼠初始肾脏肥大期间肾胰岛素样生长因子结合蛋白短暂增加
作者：
Allan Flyvbjerg;U. Kessler;Beate Dorka;Barbara Funk;Hans Ørskov;Wieland Kiess
摘要胰岛素样生长因子、胰岛素样生长因子 I 和胰岛素样生长因子 II 在循环系统和细胞外液中与六种不同类别的胰岛素样生长因子结合蛋白 (IGFBP) 结合。糖尿病肾肥大之前，肾脏胰岛素样生长因子 I 会短暂增加，这表明胰岛素样生长因子 I 具有促肾功能。为了检查 IGFBP 在糖尿病肾病初始生长和肾脏胰岛素样生长因子 I 积累中的可能参与，我们在诱导糖尿病后的前 4 天内通过配体印迹研究了大鼠肾脏 IGFBP。在肾脏和肝脏组织中鉴定出 6 个不同的条带，表观分子量值为 38-47（双峰）、34、30、24 和 20 kDa。 38-47 kDa 双联带可能对应于 IGFBP-3 的胰岛素样生长因子结合亚基，24 kDa 带对应于 IGFBP4，30 kDa 带对应于 IGFBP-1 和/或 IGFBP-2，因为大鼠中的这些 IGFBP 具有相似的分子量。在未经治疗的糖尿病大鼠中，诱导糖尿病后 24 小时可证明肾脏 30 kDa 带短暂增加，并在 48 小时后最大上升（两倍），随后在 4 天后下降至基线值。在未经治疗的糖尿病大鼠中，在糖尿病诱导后的前 2 天内，肾脏中的 38-47 kDa 双峰带也增加（两倍），随后减少。胰岛素治疗阻止了 30 kDa 和 38-47 kDa 带的增加。未经治疗的糖尿病大鼠的肾脏重量在 4 天后增加了 26%。总之，本研究表明，肥大的糖尿病肾脏中 30 kDa 和 38-47 kDa IGFBP 种类短暂增加，与先前描述的可提取肾脏胰岛素样生长因子 I 含量短暂增加同时发生。这些发现支持这样的观点：IGFBP 可能参与胰岛素样生长因子 I 的作用，并可能参与糖尿病肾胰岛素样生长因子 I 的积累。
SummaryThe insulin-like growth factors, insulin-like growth factor I and insulin-like growth factor II are bound to six distinct classes of insulin-like growth factor binding proteins (IGFBPs) in the circulation and in extracellular fluids. Diabetic renal hypertrophy is preceded by a transient increase in kidney insulin-like growth factor I suggestive of a renotropic function for insulin-like growth factor I. In order to examine a possible involvement of IGFBPs in initial diabetic kidney growth and in kidney insulin-like growth factor I accumulation, we studied rat kidney IGFBPs by ligand blotting during the first 4 days after induction of diabetes. Six distinct bands were identified in kidney and liver tissue with apparent molecular weight values of 38–47 (doublet), 34, 30, 24 and 20 kDa. The 38–47 kDa doublet band probably corresponds to the insulin-like growth factor binding subunit of IGFBP-3, the 24 kDa band to IGFBP4 and the 30 kDa band to IGFBP-1 and/or IGFBP-2, as these IGFBPs in rats have similar molecular weight. In untreated diabetic rats a transient increase in the kidney 30 kDa band was demonstrable 24 h after induction of diabetes with a maximal rise (two-fold) after 48 h, followed by a decrease to baseline values after 4 days. In untreated diabetic rats the 38–47 kDa doublet band also increased (two-fold) in kidney during the first 2 days after induction of diabetes, followed by a subsequent decrease. Insulin-treatment prevented both the increase in the 30 kDa and in the 38–47 kDa bands. Kidney weight in untreated diabetic rats increased by 26 % after 4 days. In conclusion, the present study shows a transient increase in the 30 kDa and the 38–47 kDa IGFBP species in hypertrophying diabetic kidneys, contemporarily with the previously described transient increase in extractable kidney insulin-like growth factor I content. These findings support the concept that IGFBPs may be involved in the action of insulin-like growth factor I and possibly in the diabetic kidney insulin-like growth factor I accumulation.
通过释放到培养介质中的胰岛素样生长因子载体蛋白调节胰岛素样生长因子 I 与人成纤维细胞单层培养物的结合。
DOI：
10.1172/jci112343
发表时间：
1986
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
DeVroede,MA;Tseng,LY;Katsoyannis,PG;Nissley,SP;Rechler,MM
通讯作者：
Rechler,MM
糖尿病大鼠血清中 1 型胰岛素样生长因子结合蛋白 (IGF BP) 的鉴定。
DOI：
10.1016/0006-291x(89)92304-8
发表时间：
1989
影响因子：
3.1
作者：
Unterman,TG;Oehler,DT;Becker,RE
通讯作者：
Becker,RE