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Department of Endocrinology and Diabetes, St. Thomas’ Hospital, GKT School of Medicine (H.L.S., N.C.J., F.S.-M., R.H.J., P.H.S., A.M.U.), London, United Kingdom SE1 7EH; Department of Pediatrics, University of Cambridge, Addenbrooke’s Hospital (D.B.D.), Cambridge, United Kingdom CB2 2QQ; and Department of Diabetes and Endocrinology, Royal Surrey County Hospital (D.L.R.-J.), Guildford, Surrey, United Kingdom GU2 5XX
Address all correspondence and requests for reprints to: Dr. Helen Simpson, Department of Endocrinology and Diabetes, St. Thomas’ Hospital, GKT School of Medicine, London, United Kingdom SE1 7EH. E-mail: helen.simpson{at}kcl.ac.uk.
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.
This work was supported by a fellowship from the Guys and St. Thomas’ Charitable Foundation.
Abbreviations: CV, Coefficient of variation; 
-KIC, -ketoisocaproate; MCR, metabolic clearance rate; NEFA, nonesterified fatty acids; NOLD, nonoxidative leucine disposal; Ra, production rate; Rd, rate of uptake; rh, recombinant human.
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