Effect of IGF-I on FFA and glucose metabolism in control and type 2 diabetic subjects.
The effects of insulin-like growth factor I (IGF-I) and insulin on free fatty acid (FFA) and glucose metabolism were compared in eight control and eight type 2 diabetic subjects, who received a two-step euglycemic hyperinsulinemic (0.25 and 0.5 mU x kg(-1) x min(-1)) clamp and a two-step euglycemic IGF-I (26 and 52 pmol x kg(-1) x min(-1)) clamp with [3-(3)H]glucose, [1-(14)C]palmitate, and indirect calorimetry. The insulin and IGF-I infusion rates were chosen to augment glucose disposal (R(d)) to a similar extent in control subjects. In type 2 diabetic subjects, stimulation of R(d) (second clamp step) in response to both insulin and IGF-I was reduced by approximately 40-50% compared with control subjects. In control subjects, insulin was more effective than IGF-I in suppressing endogenous glucose production (EGP) during both clamp steps. In type 2 diabetic subjects, insulin-mediated suppression of EGP was impaired, whereas EGP suppression by IGF-I was similar to that of controls. In both control and diabetic subjects, IGF-I-mediated suppression of plasma FFA concentration and inhibition of FFA turnover were markedly impaired compared with insulin (P < 0.01-0.001). During the second IGF-I clamp step, suppression of plasma FFA concentration and FFA turnover was impaired in diabetic vs. control subjects (P < 0.05-0.01).


CONCLUSIONS
1) IGF-I is less effective than insulin in suppressing EGP and FFA turnover; 2) insulin-resistant type 2 diabetic subjects also exhibit IGF-I resistance in skeletal muscle. However, suppression of EGP by IGF-I is not impaired in diabetic individuals, indicating normal hepatic sensitivity to IGF-I.
Pratipanawatr
Thongchai
T
Diabetes Division, Department of Medicine, University of Texas Health Science Center, San Antonio, Texas 78229-3900, USA.
Pratipanawatr
Wilailak
W
Rosen
Clifford
C
Berria
Rachele
R
Bajaj
Mandeep
M
Cusi
Kenneth
K
Mandarino
Lawrence
L
Kashyap
Sangeta
S
Belfort
Renata
R
DeFronzo
Ralph A
RA
D000328:Adult; D001692:Biological Transport; D001786:Blood Glucose / Q000378:metabolism*; D002153:Calorimetry, Indirect; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004351:Drug Resistance; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D005947:Glucose / Q000096:biosynthesis; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D007333:Insulin Resistance; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000032:analysis / Q000494:pharmacology*; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D014316:Tritium
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D014316:Tritium; D007334:Insulin-Like Growth Factor I; D005947:Glucose