Effects of streptozotocin-induced diabetes mellitus on growth and hepatic insulin-like growth factor I gene expression in the rat.
Poorly controlled diabetes mellitus in humans and animals is often accompanied by impaired growth. We undertook this study in young rats to determine whether the reduction in growth rate associated with streptozotocin (STZ)-induced diabetes might be related to changes in both serum insulin-like growth factor I (IGF-I) and IGF-II levels, and, if so, whether these changes reflect alterations in serum growth hormone (GH) and in hepatic IGF-I and IGF-II gene expression. Serum rat GH (rGH) levels were variable during the first 4 days after STZ administration, but during the subsequent 5- to 11-day period the mean (+/- SEM) levels in insulin-treated (DI) (21.4 +/- 4.9 ng/mL) and untreated (D) (8.5 +/- 1.5 ng/ml) diabetic rats were significantly (P less than .001) lower than in controls (C) (117.8 +/- 22.9 ng/mL). Multiple transcripts of IGF-I (7.0, 4.0, 1.9, 1.0 kb), but barely detectable amounts of IGF-II mRNA, were found in the livers of normal and diabetic rats by Northern blot analysis. Using dot blot analysis, we have shown that the abundance of total hepatic IGF-I mRNA in untreated, growth-retarded diabetic animals decreases rapidly over a period of 3 days after STZ administration. Both serum IGF-I and IGF-II levels are also diminished during this interval in these markedly hyperglycemic rats. Insulin treatment for 3 to 4 days, started either immediately (6 hours) or within 3 days after administering STZ, blunts diabetes-induced impairment of growth and restores mean hepatic IGF-I mRNA abundance to control levels, but does not normalize serum IGF-I and IGF-II concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medicine, University of Wisconsin, Center for Health Sciences, Madison.
H
H
Yang
A J
AJ
Scheff
D S
DS
Schalch
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D015152:Blotting, Northern; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000188:drug therapy / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D006130:Growth Disorders / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics; D013006:Growth Hormone / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000627:therapeutic use*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains; D013002:Somatomedins / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
D001786:Blood Glucose; D007328:Insulin; D012333:RNA, Messenger; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D013006:Growth Hormone