Tissue IGF-I Measured by Microdialysis Reflects Body Glucose Utilization After rhIGF-I Injection in Type 1 Diabetes
2015 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 100, no 11, 4299-4306 p.Article in journal (Refereed) PublishedText
Context: 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. Design: This was a single-blind placebo-controlled crossover study. Setting: The setting was a tertiary pediatric endocrine referral center. Participants: The participants were seven young male adults with type 1 diabetes. Intervention: After an overnight fast, a 6-h lasting euglycemic clamp was performed (constant insulin infusion at 0.5mU/kg x minute and variable glucose infusion rate [GIR]) and a subcutaneous injection of recombinant human (rh) IGF-I (120 mu g/kg) or saline was given after 2 hours. In parallel, tissue IGF-I levels were determined by microdialysis (md-IGF-I). Main Outcome Measures: 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 less than .001). GIR was unchanged after saline, whereas it increased 2.5-fold concomitantly with the increase in md-IGF-I (P less than .0001). In contrast, serum IGF-I was increased already at 30 minutes after rhIGF-I and reached a plateau 2-fold above baseline (P less than .0001). Conclusion: 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.
Place, publisher, year, edition, pages
ENDOCRINE SOC , 2015. Vol. 100, no 11, 4299-4306 p.
IdentifiersURN: urn:nbn:se:liu:diva-123528DOI: 10.1210/jc.2015-2070ISI: 000364925700062PubMedID: 26331550OAI: oai:DiVA.org:liu-123528DiVA: diva2:886251
Funding Agencies|Jalmari and Rauha Ahokas Foundation; Samariten Foundation; Swedish Child Diabetes Foundation (Barndiabetesfonden); Foundation Frimurare Barnhuset in Stockholm; Society for Child Care (Sallskapet Barnavard); HRH Crown Princess Lovisa Society for Medicine; Stockholm County Council; ISPAD; Biomedicum Helsinki Foundation; Finnish Foundation for Pediatric Research; NovoNordisk (Bagsvaerd, Denmark); Ipsen (Kista, Sweden)2015-12-222015-12-212015-12-22