Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022672 (acute tubular necrosis)
 2,175 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of administering insulin-like growth factor I (IGF-I) were examined in a model of ischemic acute tubular necrosis in rats. Injury was induced by 75 min of bilateral renal artery occlusion. Compared to rats administered vehicle, rats administered IGF-I (100 micrograms/day via continuous subcutaneous infusion) had significantly lower serum creatinine and blood urea nitrogen levels over the course of 7 days postocclusion. Glomerular filtration rate as determined by inulin clearance was examined on day 2 postocclusion and was significantly increased in IGF-I-treated animals (0.16 +/- 0.02 ml per min per 100 g of body weight) compared to vehicle-treated controls (0.08 +/- 0.02 ml per min per 100 g of body weight). The weight loss that occurred during the course of acute tubular necrosis was ameliorated by IGF-I. Mortality was reduced from 36.7% in vehicle-treated rats to 7.1% in rats administered IGF-I. Histologically, there was much less renal injury evident at day 7 postocclusion in the IGF-I-treated rats compared to vehicle-treated controls. In contrast, growth hormone (200 micrograms administered subcutaneously for 4 days) did not affect recovery of renal function or reduce mortality postreperfusion. This report demonstrates a beneficial effect of IGF-I administration in the setting of acute tubular necrosis. Several properties of IGF-I render it a pharmacological agent with excellent potential for treatment of this condition in humans.
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PMID:Insulin-like growth factor I accelerates recovery from ischemic acute tubular necrosis in the rat. 146 11

The renal growth hormone--insulin-like growth factor-I system in acute ischemic renal failure. Recovery from acute tubular necrosis (ATN) is accelerated by IGF-I therapy. Furthermore, the local renal growth hormone-IGF-I system may participate in the natural repair. We examined the IGF-I system in rat kidneys subjected to 60 minute ischemia compared to sham operated controls. Two days after injury, growth hormone receptor mRNA and IGF-I mRNA levels fell approximately 9 to 33% of control values. This was associated with a reduction in kidney immunoreactive IGF-I levels. In contrast, IGF-I receptor mRNA abundance was unchanged. However, plasma membrane IGF-I receptor binding on day 2 and day 7 was near double the control values (P < 0.01). Scatchard analysis revealed a near twofold increase in receptor number. Since receptor mRNA levels were unchanged, this implies receptor protein up-regulation. In contrast to unchanged IGF-I receptor mRNA levels, the abundance of mRNA levels of insulin-like growth factor binding proteins (IGFBP) -2, -3, -4 and -5 fell approximately 14 to 62% of control levels day 2 after injury (P < 0.05), suggesting reduced IGFBP production. Thus, the renal response to ischemic ATN, namely, low IGFBP mRNA levels and high IGF-I receptor number, may function to increase IGF-I bioavailability and thereby enhance the reparative actions of local and circulating IGF-I in ischemic ATN.
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PMID:Renal growth hormone--insulin-like growth factor-I system in acute renal failure. 754 60

We previously reported that following bilateral acute tubular necrosis (ATN) profound changes in the intrarenal insulin-like growth factor-I axis occurs which are unrelated to altered nutritional intake. In this current report we studied rats with unilateral ATN to assess whether these changes reflect a response to acute injury or the accompanying uremia. Compared to the contralateral kidney, the injured kidney showed an increase in IGF-I receptor number without a change in IGF-I receptor mRNA levels, a decrease in IGF-I mRNA and IGF-I protein levels, a decrease in growth hormone (GH) receptor mRNA abundance and receptor binding. There was also a decrease in IGF binding protein-2, -3 and -5 mRNA levels together with a fall in protein products. Since this unilateral ATN model excludes the influence of uremia and reduced nutritional intake, we surmised that these changes reflect a direct response to injury. Next, because of the reduced GH receptor binding noted above and the reported decrease in epidermal growth factor (EGF) expression in ATN, we tested the thesis that the low kidney IGF-I mRNA levels in ATN are partly due to a relative or absolute deficiency of these hormones. Administration of EGF or GH promptly increased ATN kidney IGF-I mRNA levels to control kidney values, lending support to the thesis. The response to EGF also suggests that the salutary effect of EGF treatment in ATN may partly be mediated by stimulating IGF-I production.
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PMID:Response of the intrarenal insulin-like growth factor-I axis to acute ischemic injury and treatment with growth hormone and epidermal growth factor. 882 16