Acute effects of insulin-like growth factor I on glucose and amino acid metabolism in the awake fasted rat: comparison with insulin

• Published in: The Journal of clinical investigation 1989-05, Vol.83 (5), p.1717-1723
• Main Authors: JACOB, R, BARRETT, E, PLEWE, G, FAGIN, K. D, SHERWIN, R. S
• Format: Article
• Language: English
• Subjects: Amino Acids; Animals; Biological and medical sciences; Blood Glucose - metabolism; Fasting; Fundamental and applied biological sciences. Psychology; General aspects. Hormone interactions. Hormone actions on several organ systems. Adaptive reactions; Humans; Hypoglycemia - chemically induced; Infusions, Intravenous; Insulin - administration & dosage; Insulin-Like Growth Factor I - administration & dosage; Kinetics; Leucine; Male; Rats; Rats, Inbred Strains; Recombinant Proteins - administration & dosage; Somatomedins - administration & dosage; Vertebrates: endocrinology
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI114072

To elucidate the acute metabolic actions of insulin-like growth factor I (IGF-I), we administered a primed (250 micrograms/kg), continuous (5 micrograms/kg.min) infusion of human recombinant (Thr 59) IGF-I or saline to awake, chronically catheterized 24-h fasted rats for 90 min. IGF-I was also infused while maintaining euglycemia (glucose clamp technique) and its effects were compared to those of insulin. IGF-I infusion caused a twofold rise in IGF-I levels and a 75-85% decrease in plasma insulin. When IGF-I alone was given, plasma glucose fell by 30-40 mg/dl (P less than 0.005) due to a transient twofold increase (P less than 0.05) in glucose uptake; hepatic glucose production and plasma FFA levels remained unchanged. IGF-I infusion with maintenance of euglycemia produced a sustained rise in glucose uptake and a marked stimulation of [3-3H]glucose incorporation into tissue glycogen, but still failed to suppress glucose production and FFA levels. IGF-I also produced a generalized 30-40% reduction in plasma amino acids, regardless of whether or not hypoglycemia was prevented. This was associated with a decrease in leucine flux and a decline in the incorporation of [1-14C]leucine into muscle and liver protein (P less than 0.05). When insulin was infused in a dosage that mimicked the rise in glucose uptake seen with IGF-I, nearly identical changes in amino acid metabolism occurred. However, insulin suppressed glucose production by 65% and FFA levels by 40% (P less than 0.001). Furthermore, insulin was less effective than IGF-I in promoting glycogen synthesis. We conclude that (a) IGF-I produces hypoglycemia by selectively enhancing glucose uptake; (b) IGF-I is relatively ineffective in suppressing hepatic glucose production or FFA levels; and (c) IGF-I, like insulin, lowers circulating amino acids by reducing protein breakdown rather than by stimulating protein synthesis. Thus, IGF-I's metabolic actions in fasted rats are readily distinguished from insulin.