Cited by 470Diabetes, Cardiovascular Risks, and LipoproteinsMetabolism, Diabetes, and CancerDiabetes Management and Research

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Impaired Insulin-Mediated Skeletal Muscle Blood Flow in Patients With NIDDM

Laakso, Markku, Edelman, Steven V, Brechtel, Ginger, Baron, Alain D·1992·Diabetes

DOI 10.2337/diab.41.9.1076

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Abstract

Patients with non-insulin-dependent diabetes metlitus (NIDDM) exhibit decreased rates of skeletal muscle insulin-mediated glucose uptake (IMGU). Because IMGU is equal to the product of the arteriovenous glucose difference (AVGΔ) across and blood flow (F) into muscle (IMGU = AVGΔ × F), reduced tissue permeability (AVGΔ) and/or glucose and insulin delivery (F) can potentially lead to decreased IMGU. The components of skeletal muscle IMGU were studied in six obese NIDDM subjects (103 ± 9 kg) and compared with those previously determined in six lean (weight 68 ± 3 kg), and six obese (94 ± 3 kg) with normal glucose tolerance. The insulin dose-response curves for whole body and leg muscle IMGU were constructed using the combined euglycemic clamp and leg balance techniques during sequential insulin infusions (range of serum insulin 130–80,000 pmol/L). In lean, obese, and NIDDM subjects, whole body IMGU, femoral AVGΔ, and leg IMGU increased in a dose-dependent fashion over the range of insulin with an ED50 of 400–500 pmol/L in lean, 1000–1200 pmol/L in obese, and 4000–7000 pmol/L in NIDDM subjects (P < 0.01 lean vs. obese and NIDDM). In lean and obese subjects, maximally effective insulin concentrations increased leg blood flow ∼2-fold from basal with an ED50 of 266 pmol/L and 957 pmol/L, respectively (P < 0.01 lean vs. obese). In contrast, leg F did not increase from the basal value in NIDDM subjects (2.7 ± 0.1 vs. 3.5 ± 0.5 dl/min, NS). In the physiological range of insulin concentrations NIDDM subjects had lower body IMGU, leg F, femoral AVGΔ, and leg IMGU than obese and lean subjects, but at maximally effective insulin concentrations, femoral AVGA did not differ between obese and NIDDM subjects. Thus, 1) both reduced skeletal muscle tissue permeability and blood flow are found in NIDDM subjects and 2) impaired insulin-mediated augmentation of skeletal muscle blood flow in obese NIDDM patients is due to the diabetic state per se and not to the obesity status. Whether reduced skeletal muscle blood flow is the result or the cause of insulin resistance in patients with NIDDM remains to be elucidated.

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“…B1 show the insulin response of the whole-body and the legs, respectively, of individuals with leanness (blue), obesity (green), and diabetes (red) (45); both have the same order of r ( q ) from left to right: lean → obese → diabetic, indicating the strengthening of insulin resistance as the…”
Influential
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BackgroundResult
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“Email: barry.scheuermann@utoledo.edu K E Y W O R D S exercise hyperemia, muscle pump, vascular tone, vasodilation mismatch between blood flow and metabolic demand is often observed in diseased states, including type 2 diabetes mellitus (Laakso et al., 1992).”
Background

Authors: Laakso, M., Edelman, S. V., Brechtel, G., & Baron, A. D.
Affiliations: University of California San Diego (US)
ORCID: Laakso, Markku
Edelman, Steven V
Venue: Diabetes
Publisher: American Diabetes Association
Published: 1992-09-01
Volume: 41
Issue: 9
Pages: 1076-1083
ISSN: 0012-1797 (ISSN-L)
1939-327X
DOI: 10.2337/diab.41.9.1076
OpenAlex: W1984231396
Cited by: 470
References: 0
Citations by year: 2026: 1 · 2025: 2 · 2024: 2 · 2023: 5 · 2022: 10 · 2021: 5 · 2020: 4 · 2019: 10 · 2018: 4 · 2017: 7 · 2016: 7 · 2015: 14 · 2014: 7 · 2013: 9 · 2012: 7
FWCI: 14.58
Type: journal article
Language: en
Open access: closed
Locations: Diabetes (publishedVersion)
PubMed (publishedVersion)
Funders: University of California, Irvine
National Institute of Diabetes and Digestive and Kidney Diseases (DK42469)
National Center for Research Resources (M-01RR00827, M01RR000827)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords: type 2 diabetes, skeletal muscle blood flow, insulin-stimulated glucose uptake, insulin resistance, obesity, arteriovenous glucose difference, insulin dose-response, euglycemic clamp, femoral blood flow, glucose tolerance
MeSH terms: Adult, Blood Glucose, Diabetes Mellitus, Type 2, Dose-Response Relationship, Drug, Glucose, Humans, Insulin, Leg, Muscles, Obesity, Regional Blood Flow

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Impaired Insulin-Mediated Skeletal Muscle Blood Flow in Patients With NIDDM

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