A Mass Spectrometric Method for Quantitation of Intact Insulin in Blood Samples

Darby, Shauna M.; Miller, Mark L.; Allen, Ralph O.; LeBeau, Marc A.

doi:10.1093/jat/25.1.8

Cited by 106 publications

(66 citation statements)

References 15 publications

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“…Average insulin levels in hyperinsulinemic malaria patients are approximately 1.6x10 -4 μM, with the highest recorded concentration at 4.7x10 -4 μM [53]. These levels contrast with blood levels of insulin in healthy patients that range from a fasting concentration of 1.7x10 -5 μM (0.1 ng/ml) to a nonfasting concentration of 5.9x10 -4 μM (3.4 ng/ml; [59]), indicating that blood levels of insulin can vary as much as 10-to 35-fold depending on nutrition and disease status.…”

Section: Insulin Signaling and Its Impact On Malaria Transmissionmentioning

confidence: 92%

The insulin signaling cascade from nematodes to mammals: Insights into innate immunity of Anopheles mosquitoes to malaria parasite infection

Luckhart

Riehle

2007

Developmental & Comparative Immunology

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As revealed over the past twenty years, the insulin signaling cascade plays a central role in regulating immune and oxidative stress responses that affect the life spans of mammals and two model invertebrates, the nematode Caenorhabitis elegans and the fruit fly Drosophila melanogaster. In mosquitoes, insulin signaling regulates key steps in egg maturation and immunity and likely affects aging, although the latter has yet to be examined in detail. Reproduction, immunity and aging critically influence the capacity of mosquitoes to effectively transmit malaria parasites. Current work has demonstrated that molecules from the invading parasite and the blood meal elicit functional responses in female mosquitoes that are regulated through the insulin signaling pathway or by crosstalk with interacting pathways. Defining the details of these regulatory interactions presents significant challenges for future research, but will increase our understanding of mosquito/malaria parasite transmission and of the conservation of insulin signaling as a key regulatory nexus in animal biology. Keywordsinsulin; Anopheles; Plasmodium; mosquito; malaria; aging; oxidative stress; innate immunity; nitric oxide; transforming growth factor; β In all well-studied metazoans, metabolism, growth, and longevity are coordinately regulated via a nexus that involves signaling cascades activated by insulin and insulin-like growth factors (IGF). Although these pathways differ in downstream physiological effects and some of their signaling proteins, the proteins themselves and their scaffolding interactions are largely conserved among model organisms ( Fig. 1), particularly in the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and the mouse Mus musculus. This review will examine our current understanding of how the insulin and IGF signaling cascades (ISC) regulate immunity in these diverse model organisms. In addition, we will explore how recent Correspondence to: Shirley Luckhart. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errorsmaybe discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Key targets of daf-16 regulation include genes for mitochondrial manganese superoxide dismutase (MnSOD) and glutathione S-transferase, which are closely linked to aging in C. elegans and other organisms, and genes for numerous C-type lectins, which play critical roles in cell adhesion and pathogen recognition [5]. Downregulation of these gene targets in daf-16 mutants would be predicted to enhance oxidative stress, which has been linked directly to aging in C. elegans [6,7], and decrease pathogen recognition [8]. Conversely, rescue of downregulated MnSOD...

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Section: Insulin Signaling and Its Impact On Malaria Transmissionmentioning

confidence: 92%

The insulin signaling cascade from nematodes to mammals: Insights into innate immunity of Anopheles mosquitoes to malaria parasite infection

Luckhart

Riehle

2007

Developmental & Comparative Immunology

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“…These methods are immunoassay [15][16][17][18], high performance liquid chromatography [19][20][21][22][23][24][25], and mass spectrometry [26][27][28][29][30]. According to the pharmacopeial method for the determination of insulin lispro, the mobile phase is constituted by phosphate buffer solution 0.1mol/L (pH 2.3) and acetonitrile.…”

Section: Introductionmentioning

confidence: 99%

Development of a New HPLC Method for the Determination of Lispro and Glargine Insulin Analogues in Pharmaceutical Preparations

Moreno¹,

Lucchesi²,

Dib³

et al. 2018

JAPLR

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A rapid, accurate and sensitive HPLC method has been developed and validated for the quantitative determination of lispro and glargine insulin analogues in pharmaceutical preparations. Pharmacopeial method for the determination of insulin lispro employed mobile phase constituted by phosphate buffer solution 0.1mol/L (pH 2.3) and acetonitrile (74 + 26, v/v) and flow rate of 0.8mL/ min. Retention time was estimated to be 25 minutes and the temperature of the column maintained to 40ºC. No pharmacopeial method was found to the determination of insulin glargine. For this reason, the aim of this study was to develop and validate a new chromatographic method for the determination of lispro and glargine insulin analogues in pharmaceutical preparations. Solutions were prepared using the mobile phase (methanol-water, 70:30) as solvent and filtered through a 0.2 µm membrane. Aliquots of 20µL were injected into the HPLC. The method validation parameters yielded good results and included range, linearity, precision, accuracy, specificity, and recovery. The calibration curves for lispro and glargine insulin analogues were linear from 0.1 to 3.5UI/ mL, with correlation coefficients of 0.9990 and 0.9995, respectively. The interday and intraday precisions (relative standard deviation) were less than 1%. The accuracy was studied and the recovery test indicated mean absolute of 100.99% and 98.76% for lispro and glargine insulin analogues, respectively. The results obtained by HPLC method were calculated by analysis of variance (ANOVA). We concluded that the HPLC method proposed is satisfactory for the quantification of lispro and glargine insulin analogues in pharmaceutical preparations. Keywords: Development of a New HPLC Method for the Determination of Lispro and Glargine Insulin Analogues in Pharmaceutical Preparations 30Copyright: ©2018 Moreno et al.the sample or the stationary phase by means of ion pairing. It should be noted that a change in buffer could result in a change in selectivity [32,33].In this work, the parameters developed for the determination of insulin analogues did not employed buffer, and the mobile phase (methanol/water, 70:30) used is simple and advantageous; the most quality control applications can be carried out with methanol/water as a mobile phase.For this reason, the purpose of the present work was to describe the development and validation of the simple and accurate HPLC method for the analysis of lispro and glargine insulin analogues in pharmaceutical preparations. Materials and Methods SamplesInsulin lispro (lot9074) and glargine insulin (lot73A) reference solutions with assigned purity of 100UI/mL as well the pharmaceutical preparations (injections) were generous donated by Eli Lilly (São Paulo, Brazil) and Sanofi-Aventis Ltda (São Paulo, Brazil). Insulin lispro injection was claimed to contain 100UI/mL of drug and glycerol, metacresol, sodium phosphate, zinc oxide and water as excipient. Insulin glargine injection was claimed to contain 100UI/mL of drug and glycerol, cresol, hydrochlor...

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“…-5 ·mol·l -1 (0.1·ng·ml -1 ) at fasting to 5.9ϫ10 -4 ·mol·l -1 [3.4 ng·ml -1 (Darby et al, 2001)] without fasting, indicating that blood levels of insulin can vary as much as 10-to 35-fold depending on nutrition and disease status.…”

Section: Introductionmentioning

confidence: 99%

Insulin regulates aging and oxidative stress in Anopheles stephensi

Kang

Mott

Tapley

et al. 2008

Journal of Experimental Biology

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SUMMARYObservations from nematodes to mammals indicate that insulin/insulin-like growth factor signaling (IIS) regulates lifespan. As in other organisms, IIS is conserved in mosquitoes and signaling occurs in multiple tissues. During bloodfeeding, mosquitoes ingest human insulin. This simple observation suggested that exogenous insulin could mimic the endogenous hormonal control of aging in mosquitoes, providing a new model to examine this phenomenon at the organismal and cellular levels. To this end, female Anopheles stephensi mosquitoes were maintained on diets containing human insulin provided daily in sucrose or three times weekly by artificial bloodmeal. Regardless of delivery route, mosquitoes provided with insulin at 1.7ϫ10 -4 and 1.7ϫ10 -3 ·mol·l -1 , doses 0.3-fold and 3.0-fold higher than non-fasting blood levels, died at a faster rate than controls. In mammals, IIS induces the synthesis of reactive oxygen species and downregulates antioxidants, events that increase oxidative stress and that have been associated with reduced lifespan. Insulin treatment of mosquito cells in vitro induced hydrogen peroxide synthesis while dietary supplementation reduced total superoxide dismutase (SOD) activity and manganese SOD activity relative to controls. The effects of insulin on mortality were reversed when diets were supplemented with manganese (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP), a cell-permeable SOD mimetic agent, suggesting that insulin-induced mortality was due to oxidative stress. In addition, dietary insulin activated Akt/protein kinase B and extracellular signal-regulated kinase (ERK) in the mosquito midgut, suggesting that, as observed in Caenorhabditis elegans, the midgut may act as a ʻsignaling centerʼ for mosquito aging.

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A Mass Spectrometric Method for Quantitation of Intact Insulin in Blood Samples

Cited by 106 publications

References 15 publications

The insulin signaling cascade from nematodes to mammals: Insights into innate immunity of Anopheles mosquitoes to malaria parasite infection

The insulin signaling cascade from nematodes to mammals: Insights into innate immunity of Anopheles mosquitoes to malaria parasite infection

Development of a New HPLC Method for the Determination of Lispro and Glargine Insulin Analogues in Pharmaceutical Preparations

Insulin regulates aging and oxidative stress in Anopheles stephensi

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