WordNet

possessing no distinctive quality or characteristics
one who does not side with any party in a war or dispute
having no net electric charge (同)electroneutral
lacking distinguishing quality or characteristics; "a neutral personality that made no impression whatever"
not supporting or favoring either side in a war, dispute, or contest
a simple protein found in fish sperm; rich in arginine; simpler in composition than globulin or albumin; counteracts the anticoagulant effect of heparin

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『中立の』;中立国の / 『公平な』,不偏不党の / (人・物が)特色のはっきりしない;(色が)はっきりしない,くすんだ / (酸性でもアルカリ性でもない)中性の / (電気が)中性の,(物体が)帯電していない / (自動車などのギアが)ニュートラルの / (文法で)中性の / 〈C〉(戦争・論争などで)中立の人;中立国民;中立国 / 〈C〉くすんだ色,灰色 / 〈U〉(自動車などのギヤの)ニュートラル(動力のかかっていない状態・位置)

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/08/09 16:37:34」(JST)

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NPH insulin (or neutral protamine Hagedorn) (also known as Humulin N, Novolin N, Novolin NPH, NPH Iletin II, and isophane insulin), is an intermediate-acting insulin given to help control the blood sugar level of those with diabetes. NPH was created in 1936 when Nordisk formulated "isophane" porcine insulin by adding neutral protamine to regular insulin.

This is a suspension of crystalline zinc insulin combined with the positively charged polypeptide, protamine. When injected subcutaneously, it has an intermediate duration of action, meaning longer than that of regular insulin, and shorter than ultralente, glargine or detemir.

History

Hans Christian Hagedorn (1888–1971) and August Krogh (1874–1949) obtained the rights for insulin from Banting and Best in Toronto. In 1923 they formed Nordisk Insulinlaboratorium, and in 1926 with August Kongsted he obtained a Danish Royal Charter as a non-profit foundation.

In 1936, Hagedorn and B. Norman Jensen discovered that the effects of injected insulin could be prolonged by the addition of protamine obtained from the "milt" or semen of river trout. The insulin would be added to the protamine, but the solution would have to be brought to pH 7 for injection. Canada later produced bok insulin, a mixture of zinc, protamine and porcine insulin. This mixture only needed to be shaken before injection.

In 1946, Nordisk was able to form crystals of protamine and insulin and marketed it in 1950 as NPH insulin. NPH insulin has the advantage that it can be mixed with an insulin that has a faster onset to complement its longer lasting action, which is the primary reason NPH remains on the market today, because manufacturers sell a variety of premixed insulin formulations. However, numerous medical studies have suggested that NPH has one of the least consistent absorption rates when injected subcutaneously, and a majority of head-to-head comparisons with Lente insulin usually found Lente provided superior glycemic control.

Eventually all animal insulins made by Novo Nordisk were replaced by synthetic, recombinant 'human' insulin. Synthetic 'human' insulin is also complexed with protamine to form NPH.

NPH insulin is cloudy and has an onset of 3–4 hours. Its peak is 4–9 hours and its duration is about 15 hours.

Administration

NPH insulin may be combined with faster acting insulin to allow more accurate dosing and better blood sugar level control. When administered this way, the two insulin types will normally be combined in the same syringe. NPH and fast-acting insulin bind when mixed, so they should not be combined until it is time to inject. Patients are instructed on the proper procedure to prepare this type of injection to minimize the likelihood of combining two types of insulin in the same vial.

Timeline

1926 Nordisk receives Danish charter to produce insulin
1936 Hagedorn discovers that adding protamine to insulin prolongs the effect of insulin
1936 Canadians D.M. Scott and A.M. Fisher formulate zinc insulin mixture and license to Novo
1946 Nordisk crystallizes a protamine and insulin mixture
1950 Nordisk markets NPH insulin
1953 Nordisk markets "Lente" zinc insulin mixtures.

References

Baganz, H. M.; Carfagno, S. C.; Cowan, B. Y.; Dillon, E. S. (1951). "NPH insulin; its comparison with previous insulin regimens". The American journal of the medical sciences 222 (1): 1–6. PMID 14846799.
Burnham, D. K. (1951). "Insulin and insulin mixtures; nph insulin". California medicine 75 (6): 412–415. PMC 1521099. PMID 14886746. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1521099.
Lacey, A. H. (1952). "A comparison of preparations of NPH insulin". The Journal of pharmacology and experimental therapeutics 105 (2): 196–202. PMID 14928221.
Deckert, T.; Hansen, B.; Kølendorf, K.; Poulsen, J. S.; Smith, M. (1982). "Absorption of NPH-insulin from subcutaneous tissue: A methodological study in pigs". Acta pharmacologica et toxicologica 51 (1): 30–37. PMID 6751023.
Kølendorf, K.; Bojsen, J. (1982). "Kinetics of subcutaneous NPH insulin in diabetics". Clinical pharmacology and therapeutics 31 (4): 494–500. PMID 7060331.

UpToDate Contents

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1. インスリンに対する過敏症反応 hypersensitivity reactions to insulins
2. 糖尿病におけるインスリン療法の一般原則 general principles of insulin therapy in diabetes mellitus
3. 妊娠前糖尿病：出産前の血糖コントロール pregestational diabetes mellitus prenatal glycemic control
4. 1型糖尿病の小児および青年における低血糖 hypoglycemia in children and adolescents with type 1 diabetes mellitus
5. 2型糖尿病における持続性高血糖のマネージメント management of persistent hyperglycemia in type 2 diabetes mellitus

English Journal

Effects of mealtime insulin aspart and bedtime neutral protamine Hagedorn insulin on postprandial coagulation and fibrinolysis in patients with type 2 diabetes.

Bladbjerg EM, Henriksen JE, Akram S, Gram J.SourceUnit for Thrombosis Research, Institute of Public Health, University of Southern Denmark, Esbjerg, Denmark Department of Clinical Biochemistry, Hospital of South West Denmark, Esbjerg, Denmark Department of Endocrinology, Odense University Hospital, Odense, Denmark Department of Endocrinology, Hospital of South West Denmark, Esbjerg, Denmark.
Diabetes, obesity & metabolism.Diabetes Obes Metab.2012 May;14(5):447-53. doi: 10.1111/j.1463-1326.2011.01547.x. Epub 2012 Jan 6.
Aim: Acute hyperglycaemia induces coagulation activation in diabetes patients. We hypothesized that rapid-acting insulin has a beneficial postprandial effect on coagulation and fibrinolysis compared with intermediate-acting insulin because of its ability to lower postprandial hyperglycaemia. Methods
PMID 22151836

A2 noradrenergic nerve cell metabolic transducer and nutrient transporter adaptation to hypoglycemia: Impact of estrogen.

Koshy Cherian A, Briski KP.SourceDepartment of Basic Pharmaceutical Sciences, College of Pharmacy, The University Louisiana at Monroe, Monroe, Louisiana.
Journal of neuroscience research.J Neurosci Res.2012 Mar 19. doi: 10.1002/jnr.23032. [Epub ahead of print]
CNS neurons exhibit sustained activation by recurring hypoglycemia in the presence of estrogen. We investigated the impact of estradiol on fuel uptake and detection of energy imbalance by hindbrain A2 metabolosensory neurons during acute vs. chronic hypoglycemia. A2 neurons were laser dissected from
PMID 22431334