Delayed Transcapillary Transport of Insulin to Muscle Interstitial Fluid in Obese Subjects

Sjöstrand, Mikaela; Gudbjörnsdottir, Soffia; Holmäng, Agneta; Lönn, Lars; Strindberg, Lena; Lönnroth, Peter

doi:10.2337/diabetes.51.9.2742

Cited by 114Diabetes, Cardiovascular Risks, and LipoproteinsAdipokines, Inflammation, and Metabolic DiseasesDiabetes Management and Research

Delayed Transcapillary Transport of Insulin to Muscle Interstitial Fluid in Obese Subjects

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Sjöstrand, Mikaela, Gudbjörnsdottir, Soffia, Holmäng, Agneta, Lönn, Lars, Strindberg, Lena, Lönnroth, Peter·2002·Diabetes

DOI 10.2337/diabetes.51.9.2742

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Abstract

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, suggesting impaired microvascular insulin delivery.
“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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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
DOI: 10.2337/diabetes.51.9.2742
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 › Epidemiology › 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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Delayed Transcapillary Transport of Insulin to Muscle Interstitial Fluid in Obese Subjects

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