TY - JOUR
T1 - Effects of recombinant human IGF-I/IGF-binding protein-3 complex on glucose and glycerol metabolism in type 1 diabetes
AU - Saukkonen, Tero
AU - Shojaee-Moradie, Fariba
AU - Williams, Rachel M.
AU - Amin, Rakesh
AU - Yuen, Kevin C.
AU - Watts, Angie
AU - Acerini, Carlo L.
AU - Umpleby, A. Margot
AU - Dunger, David B.
PY - 2006/8
Y1 - 2006/8
N2 - 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·kg-1·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·kg-1·min -1) hyperinsulinemic-euglycemic clamp. During the overnight basal steady state, rhIGF-I/IGFBP-3 dose-dependently reduced endogenous glucose production rate (Ra) (P = 0.004), while peripheral glucose uptake (Rd) was not different from placebo. The increase in glucose Rd 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 Ra, 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.
AB - 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·kg-1·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·kg-1·min -1) hyperinsulinemic-euglycemic clamp. During the overnight basal steady state, rhIGF-I/IGFBP-3 dose-dependently reduced endogenous glucose production rate (Ra) (P = 0.004), while peripheral glucose uptake (Rd) was not different from placebo. The increase in glucose Rd 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 Ra, 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.
KW - IGFBP, IGF-binding protein
KW - NEFA, nonesterified fatty acid
KW - rHIGF-I, recombinant human IGF-I
UR - http://www.scopus.com/inward/record.url?scp=33749336425&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33749336425&partnerID=8YFLogxK
U2 - 10.2337/db05-1646
DO - 10.2337/db05-1646
M3 - Article
C2 - 16873702
AN - SCOPUS:33749336425
SN - 0012-1797
VL - 55
SP - 2365
EP - 2370
JO - Diabetes
JF - Diabetes
IS - 8
ER -