Transendothelial insulin transport is not saturable in vivo. No evidence for a receptor-mediated process.

Steil, Garry M.; Ader, Marilyn; Moore, Donna; Rebrin, Kerstin; Bergman, Richard N.

doi:10.1172/jci118572

Cited by 122 publications

(126 citation statements)

References 28 publications

Supporting

Mentioning

112

Contrasting

Order By: Relevance

“…IGF-IR are reported to be present at a 10-fold excess relative to IR in endothelial cells (5). Participation by IGF-IR in facilitating insulin transport from the vasculature may explain in part the lack of saturability of insulin transport observed in some in vivo studies (8,25).…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, microdialysis and lymphatic sampling studies (4,9,10,24,25) suggest that insulin concentrations within the muscle interstitium remain at 50% or less of simultaneously measured plasma insulin even after prolonged insulin infusions. These observations suggest that insulin egress from the vasculature is a potentially important site for regulation of insulin action in muscle.…”

mentioning

confidence: 99%

See 1 more Smart Citation

The vascular endothelial cell mediates insulin transport into skeletal muscle

Wang¹,

Liu²,

Li³

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

123

View full text Add to dashboard Cite

The pathways by which insulin exits the vasculature to muscle interstitium have not been characterized. In the present study, we infused FITC-labeled insulin to trace morphologically (using confocal immunohistochemical methods) insulin transport into rat skeletal muscle. We biopsied rectus muscle at 0, 10, 30, and 60 min after beginning a continuous (10 mU·min−1·kg−1), intravenous FITC-insulin infusion (with euglycemia maintained). The FITC-insulin distribution was compared with that of insulin receptors (IR), IGF-I receptors (IGF-IR), and caveolin-1 (a protein marker for caveolae) in skeletal muscle vasculature. We observed that muscle endothelium stained strongly for FITC-insulin within 10 min, and this persisted to 60 min. Endothelium stained more strongly for FITC-insulin than any other cellular elements in muscle. IR, IGF-IR, and caveolin-1 were also detected immunohistochemically in muscle endothelial cells. We further compared their intracellular distribution with that of FITC-insulin in cultured bovine aortic endothelial cells (bAECs). Considerable colocalization of IR or IGF-IR with FITC-insulin was noted. There was some but less overlap of IR or IGF-IR or FITC-insulin with caveolin-1. Immunoprecipitation of IR coprecipitated caveolin-1, and conversely the precipitation of caveolin-1 brought down IR. Furthermore, insulin increased the tyrosine phosphorylation of caveolin-1, and filipin (which inhibits caveolae formation) blocked insulin uptake. Finally, the ability of insulin, IGF-I, and IGF-I-blocking antibody to diminish insulin transport across bAECs grown on transwell plates suggested that IGF-IR, in addition to IR, can also mediate transendothelial insulin transit. We conclude that in vivo endothelial cells rapidly take up and concentrate insulin relative to plasma and muscle interstitium and that IGF-IR, like IR, may mediate insulin transit through endothelial cells in a process involving caveolae.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The vascular endothelial cell mediates insulin transport into skeletal muscle

Wang¹,

Liu²,

Li³

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

123

View full text Add to dashboard Cite

show abstract

“…Insulin movement between the plasma and interstitial fluid, (rate constant: ) is likely diffusion based, as it is not reported to be saturated [46,47]. Insulin degradation by cells (rate constant: ) is a complex, receptor-mediated process.…”

Section: Nicing Model Of Glucose-insulin Physiologymentioning

confidence: 99%

Insulin kinetics and the Neonatal Intensive Care Insulin–Nutrition–Glucose (NICING) model

Dickson

Pretty

Alsweiler

et al. 2017

Mathematical Biosciences

View full text Add to dashboard Cite

Background: Models of human glucose-insulin physiology have been developed for a range of uses, with similarly different levels of complexity and accuracy. STAR (Stochastic Targeted) is a modelbased approach to glycaemic control. Elevated blood glucose concentrations (hyperglycaemia) are a common complication of stress and prematurity in very premature infants, and have been associated with worsened outcomes and higher mortality. This research identifies and validates the model parameters for model-based glycaemic control in neonatal intensive care.

show abstract

“…The assay uses two monoclonal antibodies that bind to different epitopes on the insulin molecule and do not bind to proinsulin. The ELISA assay cross-reacts with canine insulin and has been previously validated in our laboratory [22]. C-peptide, glucagon, cortisol and growth hormone were measured using radioimmunoassay kits (Linco Research).…”

Section: Assaysmentioning

confidence: 99%