Rodgers B D, Strack A M, Dallman M F, Hwa L, Nicoll C S
Department of Integrative Biology, University of California, Berkeley 94720-3140, USA.
Diabetes. 1995 Dec;44(12):1420-5. doi: 10.2337/diab.44.12.1420.
The experiments reported herein were conducted to determine how corticosterone regulates growth and plasma insulin-like growth factor (IGF) I and IGF-binding protein (IGFBP) concentrations in normal and streptozotocin (STZ)-induced diabetic rats. Males were bilaterally adrenalectomized (Ax) or sham Ax and given intravenous injections of 0, 30, or 65 mg STZ per kg body wt (0, 30, or 65 STZ) to induce varying degrees of insulin deficiency and implanted with 100-mg pellets containing 0, 40, or 80% corticosterone in cholesterol. Changes in plasma IGFBP concentrations were determined by Western ligand blotting or immunoblots. Neither IGFBP-5 nor IG-FBP-6 was detected in any of the treatment groups. Plasma IGFBP-2 was elevated and IGF-I was reduced in the nondiabetic Ax rats compared with sham Ax controls, but plasma IGFBP-3 and -4 were not significantly changed. Adrenalectomy had no affect on tibial growth or plasma IGFBP-1 in these animals. Plasma IGF-I, IGFBP-1 and -3, and tibial growth were equal among 0, 30, and 65 STZ Ax rats that did not receive corticosterone. Plasma IGFBP-4 was inversely related to the amount of STZ injected in these animals, and IGFBP-2 was elevated in those given the high dose of STZ. In the 0 STZ Ax rats, plasma IGF-I and IGFBP-3 increased in proportion to the corticosterone implant dose, but IGFBP-1 was unaffected. By contrast, IGF-I and IGFBP-3 were unaltered by corticosterone in the 30 STZ Ax rats, and IGFBP-1 increased in proportion with the dose of corticosterone.(ABSTRACT TRUNCATED AT 250 WORDS)
本文报道的实验旨在确定皮质酮如何调节正常大鼠和链脲佐菌素(STZ)诱导的糖尿病大鼠的生长以及血浆胰岛素样生长因子(IGF)-I和IGF结合蛋白(IGFBP)的浓度。雄性大鼠进行双侧肾上腺切除术(Ax)或假手术,然后每千克体重静脉注射0、30或65毫克STZ(0、30或65 STZ)以诱导不同程度的胰岛素缺乏,并植入含0、40或80%皮质酮的胆固醇100毫克丸剂。通过Western配体印迹法或免疫印迹法测定血浆IGFBP浓度的变化。在任何治疗组中均未检测到IGFBP-5和IGFBP-6。与假手术对照组相比,非糖尿病Ax大鼠的血浆IGFBP-2升高而IGF-I降低,但血浆IGFBP-3和-4无显著变化。肾上腺切除术对这些动物的胫骨生长或血浆IGFBP-1没有影响。未接受皮质酮的0、30和65 STZ Ax大鼠的血浆IGF-I、IGFBP-1和-3以及胫骨生长情况相同。这些动物的血浆IGFBP-4与注射的STZ量呈负相关,高剂量STZ组的IGFBP-2升高。在0 STZ Ax大鼠中,血浆IGF-I和IGFBP-3与皮质酮植入剂量成比例增加,但IGFBP-1不受影响。相比之下,30 STZ Ax大鼠的IGF-I和IGFBP-3不受皮质酮影响,而IGFBP-1与皮质酮剂量成比例增加。(摘要截短于250字)