Tissue IGF-I Measured by Microdialysis Reflects Body Glucose Utilization After rhIGF-I Injection in Type 1 Diabetes

• Published in: The journal of clinical endocrinology and metabolism Vol. 100; no. 11; pp. 4299 - 4306
• Main Authors: Ekström, Klas, Pulkkinen, Mari-Anne, Carlsson-Skwirut, Christine, Brorsson, Anna-Lena, Ma, Zhulin, Frystyk, Jan, Bang, Peter
• Format: Journal Article
• Language: English
• Published: United States Endocrine Society 01.11.2015; Copyright by The Endocrine Society
• Subjects: Adult; Blood Glucose - metabolism; Cross-Over Studies; Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - metabolism; Glucose - metabolism; Glucose Clamp Technique; Humans; Insulin-Like Growth Factor I - analysis; Insulin-Like Growth Factor I - metabolism; Insulin-Like Growth Factor I - pharmacology; Male; Medicin och hälsovetenskap; Microdialysis - methods; Muscles - metabolism; Recombinant Proteins - pharmacology; Single-Blind Method; Subcutaneous Fat - metabolism; Young Adult
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2015-2070

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 0.5 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). 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 < .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). 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.