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Cited by 303Pancreatic function and diabetesDiabetes Management and ResearchBarrier Structure and Function Studies

Insulin transport across capillaries is rate limiting for insulin action in dogs.

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Yang, Y J, Hope, I D, Ader, M, Bergman, R N·1989·Journal of Clinical Investigation
DOI 10.1172/jci114339PMC PMC304028
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Abstract

This study examined the relationship between transcapillary insulin transport and insulin action in vivo. During euglycemic clamps (n = 7) in normal conscious dogs we simultaneously measured plasma and thoracic duct lymph insulin and glucose utilization (Rd). Clamps consisted of an activation phase with constant insulin infusion (0.6 mU/kg per min) and a deactivation phase. [14C]Inulin was infused as a passively transported control substance. While [14C]inulin reached an equilibrium between plasma and lymph, steady-state (ss) plasma insulin was higher than lymph (P less than 0.05) and the ratio of 3:2 was maintained during basal, activation, and deactivation phases: 18 +/- 2 vs. 12 +/- 1, 51 +/- 2 vs. 32 +/- 1, and 18 +/- 3 vs. 13 +/- 1 microU/ml. In addition, it took longer for lymph insulin to reach ss than plasma insulin during activation and deactivation: 11 +/- 2 vs. 31 +/- 5 and 8 +/- 2 vs. 32 +/- 6 min (P less than 0.02). Rd increased from 2.6 +/- 0.1 to a ss of 6.6 +/- 0.4 mg/kg per min within 50 +/- 8 min. There was a remarkable similarity in the dynamics of insulin in lymph and Rd: the time to reach ss for Rd was not different from lymph insulin (P greater than 0.1), and the relative increases of the two measurements were similar, 164 +/- 45% and 189 +/- 29% (P greater than 0.05). While there was only a modest correlation (r = 0.78, P less than 0.01) between Rd and plasma insulin, the dynamic changes of lymph insulin and Rd showed a strong correlation (r = 0.95, P less than 0.01). The intimate relationship between lymph insulin and Rd suggests that the transcapillary insulin transport is primarily responsible for the delay in Rd. Thus, transcapillary transport may be rate limiting for insulin action, and if altered, it could be an important component of insulin resistance in obesity and diabetes mellitus.

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  • In dogs, transcapillary transport of insulin from plasma to interstitium is rate limiting for insulin-mediated glucose uptake.

    “in dogs, transcapillary transport of insulin from plasma to interstitium is rate limiting for insulin-mediated glucose uptake (8)”

    From Impaired insulin-induced sympathetic neural activation and vasodilation in skeletal muscle in obese humans. (1994) · cites this paper as [8]

  • The mechanisms that cause variable and unreliable insulin absorption from a CSII catheter into the circulation are poorly understood.

    “The mechanisms that cause variable and unreliable insulin absorption from a CSII catheter into the circulation are poorly understood.”

    From Detailed Analysis of Insulin Absorption Variability and the Tissue Response to Continuous Subcutaneous Insulin Infusion Catheter Implantation in Swine (2017) · cites this paper as [12]

    The Methods describe intravenous insulin infusion in dogs, and the Discussion concerns insulin moving from blood into the interstitium. Neither addresses variable absorption in the opposite direction—from a CSII catheter into circulation—or whether its mechanisms are poorly understood. Searches for CSII catheter absorption and subcutaneous infusion did not locate a relevant passage in our copy; page numbers were unavailable. (LLM, conf=0.77)

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Research works printed but not linked: 3

  1. Kasuga, M., Y. Fujita-Yamaguchi, D. L. Blithe, and C. R. Kahn. 1983. Tyrosine-specific protein kinase activity is associated with the purified insulin receptor. Proc. NatL. Acad. Sci. USA. 80:2137- 2141.
  2. Gaudino, M. 1949. Kinetics of distribution of inulin between two body water compartments. Proc. Soc. Exp. Biol. Med. 70:672- 674.
  3. Radziuk, J., K. H. Norwich, and M. Vranic. Measurement and validation of nonsteady turnover rates with applications to the inulin and glucose systems. Fed. Proc. 33:1855-1864.

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Authors
Yang, Y. J., Hope, I. D., Ader, M., & Bergman, R. N.
Affiliations
University of Southern California (US)
ORCID
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
1989-11-01
Volume
84
Issue
5
Pages
1620-1628
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci114339
PMC
PMC304028
OpenAlex
W2144827287
Cited by
303
References
2
Citations by year
2026: 2 · 2025: 9 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 6 · 2020: 7 · 2019: 3 · 2018: 8 · 2017: 10 · 2016: 9 · 2015: 12 · 2014: 10 · 2013: 13 · 2012: 8
FWCI
16.21
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • American Diabetes Association
  • National Institutes of Health (5t32gm008017-05, DK27619)
  • National Institute of General Medical Sciences (5T32GM08017)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK029867, DK27619, DK29867)
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords
insulin action, thoracic duct lymph, glucose utilization, euglycemic clamp, insulin resistance, dogs, inulin clearance, rate-determining step
MeSH terms
Animals, Biological Transport, Blood Glucose, Capillaries, Dogs, Glucose, Insulin, Inulin, Kinetics, Lymph, Male, Thoracic Duct, Glucose Clamp Technique

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