Tissue IGF-I Measured by Microdialysis Reflects Body Glucose Utilization After rhIGF-I Injection in Type 1 Diabetes.
BACKGROUND
Type 1 diabetes is associated with portal insulin deficiency and disturbances in the GH-IGF axis including low circulating IGF-I and GH hypersecretion. Whether peripheral hyperinsulinemia and GH hypersecretion, which are relevant to the development of vascular complications, result in elevated tissue IGF-I remains unknown.


OBJECTIVE
The purpose of this study was to determine the relationship between whole-body glucose uptake and tissue IGF-I measured by microdialysis.


METHODS
This was a single-blind placebo-controlled crossover study.


METHODS
The setting was a tertiary pediatric endocrine referral center.


METHODS
The participants were seven young male adults with type 1 diabetes.


METHODS
After an overnight fast, a 6-h lasting euglycemic clamp was performed (constant insulin infusion at 0.5 mU/kg × minute and variable glucose infusion rate [GIR]) and a subcutaneous injection of recombinant human (rh) IGF-I (120 μg/kg) or saline was given after 2 hours. In parallel, tissue IGF-I levels were determined by microdialysis (md-IGF-I).


METHODS
md-IGF-I levels in muscle and subcutaneous fat, and GIR were determined.


RESULTS
md-IGF-I levels were detectable but unchanged after saline. After rhIGF-I, muscle and subcutaneous fat md-IGF-I increased during the second and third hour and then reached a plateau up to 10-fold higher than baseline (P < .001). GIR was unchanged after saline, whereas it increased 2.5-fold concomitantly with the increase in md-IGF-I (P < .0001). In contrast, serum IGF-I was increased already at 30 minutes after rhIGF-I and reached a plateau 2-fold above baseline (P < .0001).


CONCLUSIONS
We demonstrate that md-IGF-I measurements are valid and physiologically relevant by reflecting rhIGF-I-induced glucose uptake. Future studies should be conducted to elucidate the role of local tissue IGF-I in diabetic vascular complications.
Pediatric Endocrinology Unit (K.E., M.-A.P., C.C.-S., A.-L.B.), Department of Women's and Children's Health, Karolinska Institute and Hospital, SE-171 76 Stockholm, Sweden; Children's Hospital (M.-A.P.), University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Medical Research Laboratory (Z.M., J.F.), Institute of Clinical Medicine, Faculty of Health, Aarhus University and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, DK-8000 Aarhus C, Denmark; and Division of Pediatrics (P.B.), Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-58185 Linköping, Sweden.
Klas
K
Ekström
Pediatric Endocrinology Unit (K.E., M.-A.P., C.C.-S., A.-L.B.), Department of Women's and Children's Health, Karolinska Institute and Hospital, SE-171 76 Stockholm, Sweden; Children's Hospital (M.-A.P.), University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Medical Research Laboratory (Z.M., J.F.), Institute of Clinical Medicine, Faculty of Health, Aarhus University and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, DK-8000 Aarhus C, Denmark; and Division of Pediatrics (P.B.), Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-58185 Linköping, Sweden.
Mari-Anne
MA
Pulkkinen
Pediatric Endocrinology Unit (K.E., M.-A.P., C.C.-S., A.-L.B.), Department of Women's and Children's Health, Karolinska Institute and Hospital, SE-171 76 Stockholm, Sweden; Children's Hospital (M.-A.P.), University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Medical Research Laboratory (Z.M., J.F.), Institute of Clinical Medicine, Faculty of Health, Aarhus University and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, DK-8000 Aarhus C, Denmark; and Division of Pediatrics (P.B.), Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-58185 Linköping, Sweden.
Christine
C
Carlsson-Skwirut
Pediatric Endocrinology Unit (K.E., M.-A.P., C.C.-S., A.-L.B.), Department of Women's and Children's Health, Karolinska Institute and Hospital, SE-171 76 Stockholm, Sweden; Children's Hospital (M.-A.P.), University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Medical Research Laboratory (Z.M., J.F.), Institute of Clinical Medicine, Faculty of Health, Aarhus University and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, DK-8000 Aarhus C, Denmark; and Division of Pediatrics (P.B.), Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-58185 Linköping, Sweden.
Anna-Lena
AL
Brorsson
Pediatric Endocrinology Unit (K.E., M.-A.P., C.C.-S., A.-L.B.), Department of Women's and Children's Health, Karolinska Institute and Hospital, SE-171 76 Stockholm, Sweden; Children's Hospital (M.-A.P.), University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Medical Research Laboratory (Z.M., J.F.), Institute of Clinical Medicine, Faculty of Health, Aarhus University and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, DK-8000 Aarhus C, Denmark; and Division of Pediatrics (P.B.), Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-58185 Linköping, Sweden.
Zhulin
Z
Ma
Pediatric Endocrinology Unit (K.E., M.-A.P., C.C.-S., A.-L.B.), Department of Women's and Children's Health, Karolinska Institute and Hospital, SE-171 76 Stockholm, Sweden; Children's Hospital (M.-A.P.), University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Medical Research Laboratory (Z.M., J.F.), Institute of Clinical Medicine, Faculty of Health, Aarhus University and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, DK-8000 Aarhus C, Denmark; and Division of Pediatrics (P.B.), Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-58185 Linköping, Sweden.
Jan
J
Frystyk
Pediatric Endocrinology Unit (K.E., M.-A.P., C.C.-S., A.-L.B.), Department of Women's and Children's Health, Karolinska Institute and Hospital, SE-171 76 Stockholm, Sweden; Children's Hospital (M.-A.P.), University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Medical Research Laboratory (Z.M., J.F.), Institute of Clinical Medicine, Faculty of Health, Aarhus University and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, DK-8000 Aarhus C, Denmark; and Division of Pediatrics (P.B.), Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-58185 Linköping, Sweden.
Peter
P
Bang
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis / Q000379:methods; D009132:Muscles / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D016037:Single-Blind Method; D050151:Subcutaneous Fat / Q000378:metabolism; D055815:Young Adult
D001786:Blood Glucose; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D005947:Glucose