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Delayed Transcapillary Transport of Insulin to Muscle Interstitial Fluid in Obese Subjects
Open accessAbstract
Insulin-resistant subjects have a slow onset of insulin action, and the underlying mechanism has not been determined. To evaluate whether a delayed transcapillary transport is part of the peripheral insulin resistance, we followed the kinetics of infused insulin and inulin in plasma and muscle interstitial fluid in obese insulin-resistant patients and control subjects. A total of 10 lean and 10 obese men (BMI 24 ± 0.8 vs. 32 ± 0.8 kg/m2, P < 0.001) was evaluated during a hyperinsulinemic-euglycemic clamp (insulin infusion rate 120 mU · m−2 · min−1) combined with an inulin infusion. Measurements of insulin and inulin in plasma were taken by means of arterial-venous catheterization of the forearm and microdialysis in brachioradialis muscle combined with forearm blood flow measurements with vein occlusion pletysmography. The obese subjects had a significantly lower steady-state glucose infusion rate and, moreover, demonstrated a delayed appearance of insulin (time to achieve half-maximal concentration [T1/2] 72 ± 6 vs. 46 ± 6 min in control subjects, P < 0.05) as well as inulin (T1/2 83 ± 3 vs. 53 ± 7 min, P < 0.01) in the interstitial fluid. Also, the obese subjects had a delayed onset of insulin action (T1/2 70 ± 9 vs. 45 ± 5 min in control subjects, P < 0.05), and their forearm blood flow rate was significantly lower. These results demonstrate a delayed transcapillary transport of insulin and inulin from plasma to the muscle interstitial fluid and a delayed onset of insulin action in insulin-resistant obese subjects.
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“the gradient in insulin concentration from plasma to interstitial fluid is increased in humans with prediabetes and in mouse models of prediabetes during an insulin clamp,152-154 suggesting impaired microvascular insulin delivery.”
From The Vasculature in Prediabetes (2018) · cites this paper as [152]
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Zhang, W., Adak, S., Zhang, Q., Maimaituxun, G., Xu, R., Dong, G., Debnath, A., Wang, Y. M., Singamaneni, S., Wei, X., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.07.14.738288
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Metadata
- Authors
- Sjöstrand, M., Gudbjörnsdottir, S., Holmäng, A., Lönn, L., Strindberg, L., & Lönnroth, P.
- Affiliations
- Lundberg Laboratory for Diabetes Research, Sahlgrenska University Hospital, Göteborg, Sweden
- Wallenberg Laboratory, Sahlgrenska University Hospital, Göteborg, Sweden
- Department of Radiology, Sahlgrenska University Hospital, Göteborg, Sweden
- Sahlgrenska University Hospital (SE)
- ORCID
- Strindberg, Lena
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2002-09-01
- Volume
- 51
- Issue
- 9
- Pages
- 2742-2748
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2141757949
- Cited by
- 114
- References
- 51
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 3 · 2019: 2 · 2018: 6 · 2017: 2 · 2016: 7 · 2015: 7 · 2014: 8 · 2013: 9 · 2012: 9
- FWCI
- 3.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Novo Nordisk
- Vetenskapsrådet (12206)
- Novo Nordisk Pharma
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- insulin resistance, obesity, transcapillary transport, insulin kinetics, hyperinsulinemic-euglycemic clamp, forearm blood flow, microdialysis, brachioradialis muscle
- MeSH terms
- Adult, Blood Glucose, Capillaries, Extracellular Space, Forearm, Humans, Insulin, Insulin Resistance, Inulin, Male, Obesity, Reference Values, Regional Blood Flow, Thinness, Glucose Clamp Technique, Muscle, Skeletal
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