NPH insulin
Encyclopedia
NPH insulin (also known as Humulin N, Novolin N, Novolin NPH, NPH Lletin 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
.
(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.
Novo Nordisk
Novo Nordisk manufactures and markets pharmaceutical products and services. Created in 1989 through a merger of two Danish companies dating back to the 1920s, it has become one of the world's leading companies in diabetes care, where Novo Nordisk pursues research into pulmonary delivery systems;...
formulated "isophane" porcine insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
by adding neutral protamine
Protamine
Protamines are small, arginine-rich, nuclear proteins that replace histones late in the haploid phase of spermatogenesis and are believed essential for sperm head condensation and DNA stabilization. They may allow for denser packaging of DNA in spermatozoon than histones, but they must be...
to regular insulin.
This is a suspension of crystalline zinc insulin combined with the positively charged polypeptide, protamine
Protamine
Protamines are small, arginine-rich, nuclear proteins that replace histones late in the haploid phase of spermatogenesis and are believed essential for sperm head condensation and DNA stabilization. They may allow for denser packaging of DNA in spermatozoon than histones, but they must be...
. When injected subcutaneously, it has an intermediate duration of action, meaning longer than that of regular insulin, and shorter than ultralente, glargine
Insulin glargine
Insulin glargine, marketed by Sanofi-Aventis under the name Lantus, is a long-acting basal insulin analogue, given once daily to help control the blood sugar level of those with diabetes. It consists of microcrystals that slowly release insulin, giving a long duration of action of 18 to 26 hours,...
or detemir
Insulin detemir
Insulin detemir is a long-acting human insulin analogue for maintaining the basal level of insulin. Novo Nordisk markets it under the trade name Levemir. It is an insulin analogue in which a fatty acid is bound to the lysine amino acid at position B29. It is quickly absorbed after which it binds...
.
History
Hans Christian HagedornHans Christian Hagedorn
Hans Christian Hagedorn was the creator of NPH insulin and Nordisk Insulinlaboratorium.-Biography:Hagedorn and August Krogh obtained the rights for insulin from Banting and Best in Toronto. In 1923 they formed Nordisk Insulinlaboratorium, and in 1926 with August Krogh he obtained a Danish Royal...
(1888–1971) and August Krogh (1874–1949) obtained the rights for insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
from Banting
Frederick Banting
Sir Frederick Grant Banting, KBE, MC, FRS, FRSC was a Canadian medical scientist, doctor and Nobel laureate noted as one of the main discoverers of insulin....
and Best in Toronto
Toronto
Toronto is the provincial capital of Ontario and the largest city in Canada. It is located in Southern Ontario on the northwestern shore of Lake Ontario. A relatively modern city, Toronto's history dates back to the late-18th century, when its land was first purchased by the British monarchy from...
. 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
Protamine
Protamines are small, arginine-rich, nuclear proteins that replace histones late in the haploid phase of spermatogenesis and are believed essential for sperm head condensation and DNA stabilization. They may allow for denser packaging of DNA in spermatozoon than histones, but they must be...
obtained from the "milt" or semen
Semen
Semen is an organic fluid, also known as seminal fluid, that may contain spermatozoa. It is secreted by the gonads and other sexual organs of male or hermaphroditic animals and can fertilize female ova...
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
Canada
Canada is a North American country consisting of ten provinces and three territories. Located in the northern part of the continent, it extends from the Atlantic Ocean in the east to the Pacific Ocean in the west, and northward into the Arctic Ocean...
later produced bok insulin, a mixture of zinc
Zinc
Zinc , or spelter , is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first element in group 12 of the periodic table. Zinc is, in some respects, chemically similar to magnesium, because its ion is of similar size and its only common oxidation state is +2...
, 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
Recombinant DNA
Recombinant DNA molecules are DNA sequences that result from the use of laboratory methods to bring together genetic material from multiple sources, creating sequences that would not otherwise be found in biological organisms...
'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 NovoNovo NordiskNovo Nordisk manufactures and markets pharmaceutical products and services. Created in 1989 through a merger of two Danish companies dating back to the 1920s, it has become one of the world's leading companies in diabetes care, where Novo Nordisk pursues research into pulmonary delivery systems;...
- 1946 Nordisk crystallizes a protamine and insulin mixture
- 1950 Nordisk markets NPH insulin
- 1953 Nordisk markets "Lente" zinc insulin mixtures.