Insulin-like growth factor-I and growth hormone have different effects on serum lipoproteins and secretion of lipoproteins from cultured rat hepatocytes.
GH has previously been shown to regulate serum lipoprotein levels and hepatic secretion of apolipoprotein-B (apo-B) and apo-E in the rat. The aim of this investigation was to study a possible role of insulin-like growth factor-I (IGF-I) in this regulation. Adult female rats were hypophysectomized and treated with recombinant human IGF-I (1.25 mg/kg.day) as a sc continuous infusion for 7 days. The effects of IGF-I were compared with those of bovine GH, given either as a continuous sc infusion or as two daily sc injections. All hypophysectomized rats were given replacement therapy with L-T4 and cortisol. Serum IGF-I concentrations increased to similar levels as a result of treatment with bovine GH and IGF-I. There was no effect of IGF-I on serum concentrations of glucose or insulin, whereas GH, independent of its mode of administration, increased serum insulin concentrations. Food intake was not affected by treatment with IGF-I. IGF-I had no effect on serum concentrations of cholesterol or apo-E, whereas GH given twice daily decreased serum cholesterol concentrations, and a continuous infusion of GH increased serum apo-E concentrations. Serum triglyceride and apo-B concentrations increased markedly as a result of IGF-I treatment, whereas GH had no effect on serum triglycerides, but decreased serum apo-B concentrations. Hepatocytes were isolated from hypophysectomized rats treated with L-T4 and cortisol alone or in combination with IGF-I and kept in short term cultures. In this system, IGF-I had no effect on the incorporation of [3H]glycerol in triglycerides or the mass of triglycerides in the cells and medium. There was no effect of IGF-I treatment on the secretion of apo-E or apo-B. Moreover, there was no effect of IGF-I treatment on the relationship between newly synthesized and secreted apo-B 48 and apo-B 100, as determined by [35S]methionine labeling of the proteins. In conclusion, the previously observed effects of GH on serum lipoproteins and hepatic apolipoprotein secretion does not seem to be mediated via IGF-I, but IGF-I has its own unique effects on serum triglyceride and apo-B levels. The increases in serum apo-B and serum triglyceride concentrations after IGF-I treatment were not dependent on increased hepatic secretion of apo-B or triglycerides.
Sjöberg
A
A
Department of Physiology, Göteborg University, Sweden.
Oscarsson
J
J
Olofsson
S O
SO
Edén
S
S
D000818:Animals; D001055:Apolipoproteins B / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D001057:Apolipoproteins E / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D004435:Eating; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000494:pharmacology*; D008074:Lipoproteins / Q000097:blood* / Q000378:metabolism*; D008099:Liver / Q000166:cytology* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood
D001055:Apolipoproteins B; D001057:Apolipoproteins E; D001786:Blood Glucose; D007328:Insulin; D008074:Lipoproteins; D014280:Triglycerides; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D002784:Cholesterol