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Clinical Chemistry 39: 578-582, 1993;
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Clinical Chemistry, Vol 39, 578-582, Copyright © 1993 by American Association for Clinical Chemistry

Enzyme immunoassay for intact human insulin in serum or plasma

L Andersen, B Dinesen, PN Jorgensen, F Poulsen and ME Roder
Novo Nordisk A/S, Bagsvaerd, Denmark.

We describe an enzyme-linked two-site immunoassay for quantitation of intact insulin in human serum and plasma. The method uses two murine monoclonal antibodies that bind to two different epitopes on the insulin molecule. The immunoassay is specific. Human proinsulin is not bound by the antibodies, and the binding of partially processed proinsulin intermediates is believed to be of minor clinical importance. The relative response of human, bovine, and porcine insulin is 1, 1, and 3, respectively. The assay is sensitive (detection limit 5 pmol/L), accurate (101% recovery with 50 pmol/L insulin added to samples, 95% with 100 pmol/L, and 89% with 300 pmol/L), and fast (results within 3 h), and has a high analytical capacity (done in microtiter plates). The working assay range selected is 5-600 pmol/L, corresponding to a clinically useful range. Because of its specificity, this two-site immunoassay gives results that are lower than those obtained by using a competitive radioimmunoassay, both in normal individuals and in non-insulin-dependent diabetics.


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DiabetesHome page
M. K. Dea, M. Hamilton-Wessler, M. Ader, D. Moore, L. Schaffer, M. Loftager, A. Volund, and R. N. Bergman
Albumin Binding of Acylated Insulin (NN304) Does Not Deter Action to Stimulate Glucose Uptake
Diabetes, March 1, 2002; 51(3): 762 - 769.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Endocrinol. Metab.Home page
N. Porksen, T. Grofte, J. Greisen, A. Mengel, C. Juhl, J. D. Veldhuis, O. Schmitz, M. Rossle, and H. Vilstrup
Human insulin release processes measured by intraportal sampling
Am J Physiol Endocrinol Metab, March 1, 2002; 282(3): E695 - E702.
[Abstract] [Full Text] [PDF]


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DiabetesHome page
C. Juhl, T. Grofte, P. C. Butler, J. D. Veldhuis, O. Schmitz, and N. Porksen
Effects of Fasting on Physiologically Pulsatile Insulin Release in Healthy Humans
Diabetes, February 1, 2002; 51(90001): S255 - 257.
[Abstract] [Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
S. H. Song, L. Kjems, R. Ritzel, S. M. McIntyre, M. L. Johnson, J. D. Veldhuis, and P. C. Butler
Pulsatile Insulin Secretion by Human Pancreatic Islets
J. Clin. Endocrinol. Metab., January 1, 2002; 87(1): 213 - 221.
[Abstract] [Full Text] [PDF]


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Diabetes CareHome page
C. H. Gravholt, B. Nyholm, B. Saltin, O. Schmitz, and J. S. Christiansen
Muscle Fiber Composition and Capillary Density in Turner Syndrome: Evidence of increased muscle fiber size related to insulin resistance
Diabetes Care, September 1, 2001; 24(9): 1668 - 1673.
[Abstract] [Full Text] [PDF]


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DiabetesHome page
L. L. Kjems, B. M. Kirby, E. M. Welsh, J. D. Veldhuis, M. Straume, S. S. McIntyre, D. Yang, P. Lefebvre, and P. C. Butler
Decrease in {beta}-Cell Mass Leads to Impaired Pulsatile Insulin Secretion, Reduced Postprandial Hepatic Insulin Clearance, and Relative Hyperglucagonemia in the Minipig
Diabetes, September 1, 2001; 50(9): 2001 - 2012.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Endocrinol. Metab.Home page
K. Fosgerau, S. D. Mittelman, A. Sunehag, M. K. Dea, K. Lundgren, and R. N. Bergman
Lack of hepatic "interregulation" during inhibition of glycogenolysis in a canine model
Am J Physiol Endocrinol Metab, August 1, 2001; 281(2): E375 - E383.
[Abstract] [Full Text] [PDF]


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GlycobiologyHome page
T. Osterbye, K. H. Jorgensen, P. Fredman, J. Tranum-Jensen, A. Kaas, J. Brange, J. L. Whittingham, and K. Buschard
Sulfatide promotes the folding of proinsulin, preserves insulin crystals, and mediates its monomerization
Glycobiology, June 1, 2001; 11(6): 473 - 479.
[Abstract] [Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
C. H. Gravholt, N. Møller, M. D. Jensen, J. S. Christiansen, and O. Schmitz
Physiological Levels of Glucagon Do Not Influence Lipolysis in Abdominal Adipose Tissue as Assessed by Microdialysis
J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 2085 - 2089.
[Abstract] [Full Text]


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DiabetesHome page
C. Hauerslev Foss, E. Vestbo, A. Frøland, H.J. Gjessing, C.E. Mogensen, and E.M. Damsgaard
Autonomic Neuropathy in Nondiabetic Offspring of Type 2 Diabetic Subjects Is Associated With Urinary Albumin Excretion Rate and 24-h Ambulatory Blood Pressure: The Fredericia Study
Diabetes, March 1, 2001; 50(3): 630 - 636.
[Abstract] [Full Text]


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Diabetes CareHome page
K. Hermansen, M. Søndergaard, L. Høie, M. Carstensen, and B. Brock
Beneficial Effects of a Soy-Based Dietary Supplement on Lipid Levels and Cardiovascular Risk Markers in Type 2 Diabetic Subjects
Diabetes Care, February 1, 2001; 24(2): 228 - 233.
[Abstract] [Full Text]


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NeurologyHome page
J. Rattya, J. Turkka, A. J. Pakarinen, M. Knip, M. A. Kotila, O. Lukkarinen, V.V. Myllyla, and J. I.T. Isojarvi
Reproductive effects of valproate, carbamazepine, and oxcarbazepine in men with epilepsy
Neurology, January 9, 2001; 56(1): 31 - 36.
[Abstract] [Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
S. H. Song, S. S. McIntyre, H. Shah, J. D. Veldhuis, P. C. Hayes, and P. C. Butler
Direct Measurement of Pulsatile Insulin Secretion from the Portal Vein in Human Subjects
J. Clin. Endocrinol. Metab., December 1, 2000; 85(12): 4491 - 4499.
[Abstract] [Full Text]


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StrokeHome page
B. Lindahl, B. Dinesen, M. Eliasson, M. Roder, G. Hallmans, and B. Stegmayr
High Proinsulin Levels Precede First-Ever Stroke in a Nondiabetic Population
Stroke, December 1, 2000; 31(12): 2936 - 2941.
[Abstract] [Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
S. A. Urhammer, T. Hansen, K. Borch-Johnsen, and O. Pedersen
Studies of the Synergistic Effect of the Trp/Arg64 Polymorphism of the {beta}3-Adrenergic Receptor Gene and the -3826 A->G Variant of the Uncoupling Protein-1 Gene on Features of Obesity and Insulin Resistance in a Population-Based Sample of 379 Young Danish Subjects
J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3151 - 3154.
[Abstract] [Full Text]


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Am. J. Physiol. Endocrinol. Metab.Home page
T. Laedtke, L. Kjems, N. Porksen, O. Schmitz, J. Veldhuis, P. C. Kao, and P. C. Butler
Overnight inhibition of insulin secretion restores pulsatility and proinsulin/insulin ratio in type 2 diabetes
Am J Physiol Endocrinol Metab, September 1, 2000; 279(3): E520 - E528.
[Abstract] [Full Text] [PDF]


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Arch. Dis. Child. Fetal Neonatal Ed.Home page
F. Ebbesen, A. Joergensen, E. Hoseth, P.-H. Kaad, M. Moeller, V. Holsteen, and M. Rix
Neonatal hypoglycaemia and withdrawal symptoms after exposure in utero to valproate
Arch. Dis. Child. Fetal Neonatal Ed., September 1, 2000; 83(2): 124F - 129.
[Abstract] [Full Text]


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Am. J. Physiol. Endocrinol. Metab.Home page
C. B. Juhl, N. Porksen, J. Sturis, A. P. Hansen, J. D. Veldhuis, S. Pincus, M. Fineman, and O. Schmitz
High-frequency oscillations in circulating amylin concentrations in healthy humans
Am J Physiol Endocrinol Metab, March 1, 2000; 278(3): E484 - E490.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Endocrinol. Metab.Home page
N. Porksen, C. Juhl, M. Hollingdal, S. M. Pincus, J. Sturis, J. D. Veldhuis, and O. Schmitz
Concordant induction of rapid in vivo pulsatile insulin secretion by recurrent punctuated glucose infusions
Am J Physiol Endocrinol Metab, January 1, 2000; 278(1): E162 - E170.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Endocrinol. Metab.Home page
C. H. Gravholt, O. Schmitz, L. Simonsen, J. Bulow, J. S. Christiansen, and N. Moller
Effects of a physiological GH pulse on interstitial glycerol in abdominal and femoral adipose tissue
Am J Physiol Endocrinol Metab, November 1, 1999; 277(5): E848 - E854.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Endocrinol. Metab.Home page
J. M. Richey, M. Ader, D. Moore, and R. N. Bergman
Angiotensin II induces insulin resistance independent of changes in interstitial insulin
Am J Physiol Endocrinol Metab, November 1, 1999; 277(5): E920 - E926.
[Abstract] [Full Text] [PDF]


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Am. J. Clin. Nutr.Home page
C. Thomsen, O. Rasmussen, T. Lousen, J. J Holst, S. Fenselau, J. Schrezenmeir, and K. Hermansen
Differential effects of saturated and monounsaturated fatty acids on postprandial lipemia and incretin responses in healthy subjects
Am. J. Clinical Nutrition, June 1, 1999; 69(6): 1135 - 1143.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Endocrinol. Metab.Home page
X.-J. Zhang, D. L. Chinkes, S. E. Wolf, and R. R. Wolfe
Insulin but not growth hormone stimulates protein anabolism in skin wound and muscle
Am J Physiol Endocrinol Metab, April 1, 1999; 276(4): E712 - E720.
[Abstract] [Full Text] [PDF]


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PediatricsHome page
J. Rättyä, L. Vainionpää, M. Knip, P. Lanning, and J. I. T. Isojärvi
The Effects of Valproate, Carbamazepine, and Oxcarbazepine on Growth and Sexual Maturation in Girls With Epilepsy
Pediatrics, March 1, 1999; 103(3): 588 - 593.
[Abstract] [Full Text]


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J. Clin. Endocrinol. Metab.Home page
S. A. Urhammer, T. Hansen, C. T. Ekstrøm, H. Eiberg, and O. Pedersen
The Ala/Val98 Polymorphism of the Hepatocyte Nuclear Factor-1{alpha} Gene Contributes to the Interindividual Variation in Serum C-Peptide Response during an Oral Glucose Tolerance Test: Evidence from Studies of 231 Glucose-Tolerant First Degree Relatives of Type 2 Diabetic Probands
J. Clin. Endocrinol. Metab., December 1, 1998; 83(12): 4506 - 4509.
[Abstract] [Full Text]


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J. Clin. Endocrinol. Metab.Home page
S. A. Urhammer, A. M. Møller, B. Nyholm, C. T. Ekstrøm, H. Eiberg, J. O. Clausen, T. Hansen, O. Pedersen, and O. Schmitz
The Effect of Two Frequent Amino Acid Variants of the Hepatocyte Nuclear Factor-1{alpha} Gene on Estimates of the Pancreatic {beta}-Cell Function in Caucasian Glucose-Tolerant First-Degree Relatives of Type 2 Diabetic Patients
J. Clin. Endocrinol. Metab., November 1, 1998; 83(11): 3992 - 3995.
[Abstract] [Full Text]


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Clin. Chem.Home page
M. Deberg, P. Houssa, B. H. Frank, F. Sodoyez-Goffaux, and J.-C. Sodoyez
Highly specific radioimmunoassay for human insulin based on immune exclusion of all insulin precursors
Clin. Chem., July 1, 1998; 44(7): 1504 - 1513.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Endocrinol. Metab.Home page
E. Christiansen, L. L. Kjems, A. Volund, A. Tibell, C. Binder, and S. Madsbad
Insulin secretion rates estimated by two mathematical methods in pancreas-kidney transplant recipients
Am J Physiol Endocrinol Metab, April 1, 1998; 274(4): E716 - E725.
[Abstract] [Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
R. Hovorka, L. Chassin, S. D. Luzio, R. Playle, and D. R. Owens
Pancreatic {beta}-Cell Responsiveness during Meal Tolerance Test: Model Assessment in Normal Subjects and Subjects with Newly Diagnosed Noninsulin-Dependent Diabetes Mellitus
J. Clin. Endocrinol. Metab., March 1, 1998; 83(3): 744 - 750.
[Abstract] [Full Text]


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Am. J. Physiol. Endocrinol. Metab.Home page
X.-J. Zhang, D. L. Chinkes, D. Doyle Jr., and R. R. Wolfe
Metabolism of skin and muscle protein is regulated differently in response to nutrition
Am J Physiol Endocrinol Metab, March 1, 1998; 274(3): E484 - E492.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Endocrinol. Metab.Home page
N. Porksen, B. Nyholm, J. D. Veldhuis, P. C. Butler, and O. Schmitz
In humans at least 75% of insulin secretion arises from punctuated insulin secretory bursts
Am J Physiol Endocrinol Metab, November 1, 1997; 273(5): E908 - E914.
[Abstract] [Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
C. H. Gravholt, R. W. Naeraa, S. Fisker, and J. S. Christiansen
Body Composition and Physical Fitness Are Major Determinants of the Growth Hormone-Insulin-Like Growth Factor Axis Aberrations in Adult Turner's Syndrome, with Important Modulations by Treatment with 17{beta}-Estradiol
J. Clin. Endocrinol. Metab., August 1, 1997; 82(8): 2570 - 2577.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
J. S. Jensen
Renal and Systemic Transvascular Albumin Leakage in Severe Atherosclerosis
Arterioscler Thromb Vasc Biol, September 1, 1995; 15(9): 1324 - 1329.
[Abstract] [Full Text]




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