Nutrition and somatomedin. XXI. Insulin-like growth factor-I and somatomedin inhibitor in streptozotocin-diabetic rats: relation to ketogenesis and gluconeogenesis.
Diabetes is associated with a fall in serum insulin-like growth factor-I (IGF-1) and a rise in somatomedin inhibitor, a circulating factor(s) of approximately 30,000 MW that is released by the liver and can antagonize both somatomedin and insulin action. Levels of inhibitor correlate with levels of glucose, beta-hydroxybutyrate, and weight loss. To study pathways that could underlie the fall in IGF-1 and rise in inhibitor, the effects of metabolic inhibitors on circulating metabolic fuels, serum IGF-1, and serum somatomedin inhibitor activity were studied. Rats given streptozotocin exhibited weight loss of 14% +/- 0.1%, glucose 457 +/- 26 mg/dL, and beta-hydroxybutyrate (BOHB) 6.3 +/- 0.5 mmol/L. Somatomedin inhibitor was separated from IGF-1 by size exclusion HPLC at pH 3; IGF-1 was measured by RIA, and somatomedin inhibitor by cartilage bioassay. Diabetic animals exhibited a fall in IGF-1 to 76% of normal (P less than .02) and a rise in inhibitor to 270% of normal (P less than .01). 3-Mercaptopicolinic (3-MPA) acid, an inhibitor of gluconeogenesis, lowered glucose to 68 +/- 2 mg/dL and BOHB to 0.96 +/- 0.09 mmol/L (both P less than .01 v diabetic), but levels of inhibitor did not fall. Nicotinic acid, an inhibitor of lipolysis, did not affect glucose but reduced BOHB to 0.42 +/- 0.02 mmol/L; somatomedin inhibitor fell 19% below diabetic levels (NS) but remained above normal (P less than .01). In contrast, inhibition of fatty acid oxidation with methyl-2-tetradecylglycidate reduced glucose to 191 +/- 18 mg/dL but lowered BOHB to normal, 0.16 +/- 0.02 mmol/L, accompanied by normalization of somatomedin inhibitor levels (152% +/- 33% of normal, NS). Below 1.0 mmol/L BOHB, somatomedin inhibitor and BOHB were strongly correlated (r = .67, P less than .001); no comparable relation was found with glucose.(ABSTRACT TRUNCATED AT 250 WORDS)
Gagliardi
A R
AR
Department of Medicine, Emory University School of Medicine, Atlanta, GA.
Goldstein
S
S
Phillips
L S
LS
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects; D004852:Epoxy Compounds / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism; D005943:Gluconeogenesis / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000172:deficiency / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007657:Ketone Bodies / Q000096:biosynthesis; D008099:Liver / Q000378:metabolism; D008297:Male; D009525:Niacin / Q000494:pharmacology; D009752:Nutritional Status; D010848:Picolinic Acids / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013002:Somatomedins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology*
D004852:Epoxy Compounds; D005227:Fatty Acids; D007328:Insulin; D007657:Ketone Bodies; D010848:Picolinic Acids; D011422:Propionates; D013002:Somatomedins; C021250:somatomedin inhibitor; D009525:Niacin; D007334:Insulin-Like Growth Factor I; C008363:3-mercaptopicolinic acid; C017522:methyl 2-tetradecylglycidate