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Tissue IGF-I Measured by Microdialysis Reflects Body Glucose Utilization After rhIGF-I Injection in Type 1 Diabetes
Karolinska institutet.ORCID iD: 0000-0002-8136-6340
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2015 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 100, no 11, p. 4299-306Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2015. Vol. 100, no 11, p. 4299-306
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:du-27248DOI: 10.1210/jc.2015-2070PubMedID: 26331550OAI: oai:DiVA.org:du-27248DiVA, id: diva2:1188700
Available from: 2018-03-08 Created: 2018-03-08 Last updated: 2018-03-28Bibliographically approved

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