Quantification of insulin

Takayama, Masayuki; Yamauchi, Kazuyo; Aizawa, Toru

doi:10.1111/dme.12337

Cited by 14 publications

(22 citation statements)

References 5 publications

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“…Typical injections of a short-acting insulin (formulated as 100 IU/ ml, which is equivalent to 600 M; Ref. 45) deliver~10 IU (60 nmol) of the hormone at the injection site (20), which even if significantly diluted results in local concentrations in the mid-micromolar range. Strikingly, the process whereby such insulin injected below the skin reaches the circulation has not been properly documented.…”

Section: Introductionmentioning

confidence: 99%

Insulin uptake and action in microvascular endothelial cells of lymphatic and blood origin

Jaldín-Fincati

Pereira

Bilan

et al. 2018

American Journal of Physiology-Endocrinology and Metabolism

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Whereas the blood microvasculature constitutes a biological barrier to the action of blood-borne insulin on target tissues, the lymphatic microvasculature might act as a barrier to subcutaneously administrated insulin reaching the circulation. Here, we evaluate the interaction of insulin with primary microvascular endothelial cells of lymphatic [human dermal lymphatic endothelial cells (HDLEC)] and blood [human adipose microvascular endothelial cells (HAMEC)] origin, derived from human dermal and adipose tissues, respectively. HDLEC express higher levels of insulin receptor and signal in response to insulin as low as 2.5 nM, while HAMEC only activate signaling at 100 nM (a dose that blood vessels do not normally encounter). Low insulin acts specifically through the insulin receptor, while supraphysiological insulin acts through both the IR and insulin growth factor-1 receptor. At supraphysiological or injection site-compatible doses pertinent to lymphatic microvessels, insulin enters HAMEC and HDLEC via fluid-phase endocytosis. Conversely, at physiologically circulating doses (0.2 nM) pertinent to blood microvessels, insulin enters HAMEC through a receptor-mediated process requiring IR autophosphorylation but not downstream insulin signaling. At physiological doses, internalized insulin is barely degraded and is instead released intact to the extracellular medium. In conclusion, we document for the first time the mechanism of interaction of insulin with lymphatic endothelial cells, which may be relevant to insulin absorption during therapeutic injections. Furthermore, we describe distinct action and uptake routes for insulin at physiological and supraphysiological doses in blood microvascular endothelial cells, providing a potential explanation for previously conflicting studies on endothelial insulin uptake.

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Section: Introductionmentioning

confidence: 99%

Insulin uptake and action in microvascular endothelial cells of lymphatic and blood origin

Jaldín-Fincati

Pereira

Bilan

et al. 2018

American Journal of Physiology-Endocrinology and Metabolism

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“…All concentrations were converted to the same unit (μIU/mL for insulin and pg/mL for PP) as follows: for insulin, values in pmol/L were divided by 6.0 to convert them to μIU/mL. Based on a molecular weight of 5807.57 Da, 1 IU insulin equals 0.0347 mg ( 59–61 ). For PP, values in pmol/L were divided by 0.239 to convert them to pg/mL based on a molecular weight of 4181.77 Da ( 60 ).…”

Section: Methodsmentioning

confidence: 99%

Endocrine Cephalic Phase Responses to Food Cues: A Systematic Review

Lasschuijt

Mars

Graaf

et al. 2020

Advances in Nutrition

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Cephalic phase responses (CPRs) are conditioned anticipatory physiological responses to food cues. They occur before nutrient absorption and are hypothesized to be important for satiation and glucose homeostasis. Cephalic phase insulin responses (CPIRs) and pancreatic polypeptide responses (CPPPRs) are found consistently in animals, but human literature is inconclusive. We performed a systematic review of human studies to determine the magnitude and onset time of these CPRs. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to develop a search strategy. The terms included in the search strategy were cephalic or hormone response or endocrine response combined with insulin and pancreatic polypeptide (PP). The following databases were searched: Scopus (Elsevier), Science Direct, PubMed, Google Scholar, and The Cochrane Library. Initially, 582 original research articles were found, 50 were included for analysis. An insulin increase (≥1μIU/mL) was observed in 41% of the treatments (total n = 119). In 22% of all treatments the increase was significant from baseline. The median (IQR) insulin increase was 2.5 (1.6–4.5) μIU/mL, 30% above baseline at 5± 3 min after food cue onset (based on study treatments that induced ≥1 μIU/mL insulin increase). A PP increase (>10 pg/mL) was found in 48% of the treatments (total n = 42). In 21% of the treatments, the increase was significant from baseline. The median (IQR) PP increase was 99 (26–156) pg/mL, 68% above baseline at 9± 4 min after food cue onset (based on study treatments that induced ≥1 μIU/mL insulin increase). In conclusion, CPIRs are small compared with spontaneous fluctuations. Although CPPPRs are of a larger magnitude, both show substantial variation in magnitude and onset time. We found little evidence for CPIR or CPPPR affecting functional outcomes, that is, satiation and glucose homeostasis. Therefore, CPRs do not seem to be biologically meaningful in daily life.

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“…4,19 Some common insulin analogues include insulin lispro (Humalog®), insulin aspart (Novorapid®), insulin glulisine (Apidra®), and insulin glargine (Lantus®), all of which have a defined potency of 1 μIU/mL = 6.00 pmol/L, 4 while insulin detemir (Levemir®) has a lower potency at 1 μIU/mL = 24.0 pmol/L. 4…”

Section: Insulin Analoguesmentioning

confidence: 99%

“…4,20 Another critical issue in this regard is that insulin assays do not always measure, or fully measure, insulin analogues. 4 Further discussion of the measurement and potency of insulin analogues is outside the scope of this commentary. However, caution is recommended when interpreting laboratory results for insulin analogues for these reasons.…”

Section: Insulin Analoguesmentioning

confidence: 99%

Insulin Units and Conversion Factors: A Story of Truth, Boots, and Faster Half-Truths

Knopp

Holder-Pearson

Chase

2018

J Diabetes Sci Technol

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Conventional insulin concentration units (IU/mL or just U/mL) are bioefficacy based, whereas the Système International (SI) units (pmol/L) are mass based. In converting between these two different approaches, there are at least 2 well-accepted conversion factors, where there should be only 1. The correct value is not the most-used or well-accepted using online calculators, some journal styles, laboratory reports, and published articles. In short, an incorrect insulin conversion factor is widely used which underreports insulin concentrations by ~15%, with potentially significant research and clinical implications. This short commentary describes the history of insulin IU definitions and conversion factors, and highlights the widespread nature of conversion factor misuse, to provoke deeper interest and thought regarding numbers we so often use without thinking.

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Quantification of insulin

Cited by 14 publications

References 5 publications

Insulin uptake and action in microvascular endothelial cells of lymphatic and blood origin

Insulin uptake and action in microvascular endothelial cells of lymphatic and blood origin

Endocrine Cephalic Phase Responses to Food Cues: A Systematic Review

Insulin Units and Conversion Factors: A Story of Truth, Boots, and Faster Half-Truths

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