Effects of recombinant human IGF-I/IGF-binding protein-3 complex on glucose and glycerol metabolism in type 1 diabetes.
Recombinant human IGF-I (rhIGF-I) complexed with its natural binding protein IGF-binding protein (IGFBP)-3 (rhIGF-I/IGFBP-3) is a novel formulation that has been shown to improve insulin sensitivity in type 1 diabetes, yet the mechanisms are not clear. We used stable isotopes to investigate the effects of rhIGF-I/IGFBP-3 on glucose and glycerol metabolism in type 1 diabetes. Fifteen subjects (age 13-24 years; 10 males) were studied on three occasions in random order. Each study period lasted for two days, and an injection of either placebo or rhIGF-I/IGFBP-3 (0.1-0.8 mg x kg(-1) x day (-1)) was given subcutaneously at 6:00 p.m. on days 1 and 2. Following the second injection, the subjects were kept euglycemic overnight by a variable rate insulin infusion, followed by a 4-h, two-step (insulin 0.6 and 1.5 mU x kg(-1) x min (-1)) hyperinsulinemic-euglycemic clamp. During the overnight basal steady state, rhIGF-I/IGFBP-3 dose-dependently reduced endogenous glucose production rate (R(a)) (P = 0.004), while peripheral glucose uptake (R(d)) was not different from placebo. The increase in glucose R(d) during hyperinsulinemic clamp was greater following rhIGF-I/IGFBP-3 than placebo, both during the first (P = 0.008) and second step (P = 0.008) of the clamp. No significant differences were found in glycerol R(a), a measure of lipolysis, between rhIGF-I/IGFBP-3 and placebo. In conclusion, rhIGF-I/IGFBP-3 enhances glucose metabolism by controlling both endogenous glucose output and peripheral glucose uptake.
Saukkonen
Tero
T
Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK.
Shojaee-Moradie
Fariba
F
Williams
Rachel M
RM
Amin
Rakesh
R
Yuen
Kevin C
KC
Watts
Angie
A
Acerini
Carlo L
CL
Umpleby
A Margot
AM
Dunger
David B
DB
D020155:3-Hydroxybutyric Acid / Q000097:blood; D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005947:Glucose / Q000096:biosynthesis / Q000378:metabolism*; D015309:Glucose Clamp Technique; D005990:Glycerol / Q000378:metabolism*; D006801:Humans; D007279:Injections, Subcutaneous; D007328:Insulin / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000008:administration & dosage*; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage*; D008066:Lipolysis; D008297:Male; D010919:Placebos; D011994:Recombinant Proteins / Q000008:administration & dosage; D012727:Sex Characteristics
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D010919:Placebos; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D005947:Glucose; D005990:Glycerol; D020155:3-Hydroxybutyric Acid