Insulin-like growth factor I has a direct effect on glucose and protein metabolism, but no effect on lipid metabolism in type 1 diabetes.
There is evidence of a metabolic role for IGF-I in type 1 diabetes, but it is unclear whether IGF-I acts indirectly by reducing GH secretion or has direct effects. Using stable isotopes we have investigated, on three separate occasions, the effect of a pulse of recombinant human GH, a sc injection of recombinant human IGF-I, and a placebo on glucose, lipid, and protein metabolism in subjects with type 1 diabetes during a basal insulin infusion and a hyperinsulinemic euglycemic clamp. Endogenous GH secretion was suppressed with octreotide. IGF-I reduced the hepatic glucose production rate (Ra), increased peripheral glucose uptake, and reduced protein breakdown during the basal insulin infusion (P < 0.05, P < 0.005, and P < 0.05, respectively, vs. placebo) and the hyperinsulinemic euglycemic clamp (P < 0.05, P < 0.005, and P < 0.05, respectively, vs. placebo). IGF-I had no effect on glycerol Ra, an index of lipolysis. GH increased glucose and glycerol Ra during the basal insulin infusion (P < 0.005 vs. placebo study), but the effects were no different from placebo during the clamp. In conclusion, IGF-I had a direct effect on glucose and protein metabolism, which was maintained during the hyperinsulinemic euglycemic clamp. This suggests that IGF-I acts in concert with insulin and may have an important role in maintaining glucose homeostasis and protein metabolism in type 1 diabetes.
Simpson
Helen L
HL
Department of Endocrinology and Diabetes, St. Thomas' Hospital, GKT School of Medicine, London, United Kingdom SE1 7EH. helen.simpson@kcl.ac.uk
Jackson
Nicola C
NC
Shojaee-Moradie
Fariba
F
Jones
Richard H
RH
Russell-Jones
David L
DL
Sönksen
Peter H
PH
Dunger
David B
DB
Umpleby
A Margot
AM
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D005990:Glycerol / Q000097:blood; D006706:Homeostasis; D019382:Human Growth Hormone / Q000097:blood / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000494:pharmacology*; D007700:Kinetics; D007930:Leucine / Q000097:blood; D008055:Lipids / Q000097:blood*; D008066:Lipolysis; D008099:Liver / Q000378:metabolism; D008657:Metabolic Clearance Rate; D010084:Oxidation-Reduction; D010919:Placebos; D011506:Proteins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D008055:Lipids; D010919:Placebos; D011506:Proteins; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D005934:Glucagon; D007930:Leucine; D005947:Glucose; D005990:Glycerol