Rayos, Devonn Jay C.

(19-21832)

BS-ChE 4A

A Report on Recombinant Human Insulin And Their Place in Diabetes Therapy

The gold standard of care for persons with type 1 and severe type 2 diabetes is
insulin replacement therapy. Previously, cow and pig pancreatic tissue were used to
make the hormone. Later, human insulin made from a semi-synthetic version of animal
insulin. Recombinant human insulin became widely available through biosynthesis in
microorganisms (Yeast, Escherichia coli) as a result of the advancement of
recombinant DNA technology, permitting consistent and reasonably priced supplies of
the hormone globally. One of the earliest biotech products was recombinant human
insulin. It was created in response to the demand for a reliable and enough supply on a
global scale. Animal insulins and semi-synthetic insulins created by modifying animal
insulins were superseded by recombinant human insulin. Regulatory approval was
necessary for bioequivalence research. Throughout these operations, three reference
products—Humulin® (Eli Lilly and Co.), Novolin® (NovoNordisk), and Insuman®
(Sanofi)—were synthesized independently.

People with diabetes didn't survive very long since there wasn't much that could
be done to treat them until the discovery of insulin in 1921. The conventional course of
therapy for diabetes was to place patients on extremely restricted diets with little to no
carbs. The patients might live a few more years even though they couldn't be saved.
Patients have occasionally even died from malnutrition as a result of tight diets (some of
which recommended as few as 450 calories per day!). Later, in 1889, two German
scientists by the names of Oskar Minkowski and Joseph von Mering discovered that
after having their pancreatic glands removed, dogs quickly acquired signs of diabetes
and finally passed away. This gave rise to the theory that "pancreatic chemicals" like
insulin were created in the pancreas. Later, the main objective of the search was the
Langerhans islands (a fancy name for clusters of specialized cells in the pancreas).
According to Sir Edward Albert Sharpey-hypothesis Shafer's from 1910, diabetics'
pancreases are deficient in just one molecule. He chose to call this molecule insulin,
which is derived from the Latin word insula, which means "island." The news about insulin
spread around the world like wildfire. Then, the first genetically engineered, synthetic
“human” insulin was produced in 1978 using E. coli bacteria to produce the insulin. Eli
Lilly went on in 1982 to sell the first commercially available biosynthetic human insulin
under the brand name Humulin.

Recombinant human insulin is produced by inserting a gene encoding the pre-

pro-insulin precursor protein into a DNA vector, which is subsequently inserted into a
host. The culture and fermentation conditions are closely controlled during the product
synthesis to enhance yields. A fusion protein made by fermentation is transformed into
bioactive human insulin through a post-translational process. The final phase in the
production process is the multi-stage purification of human insulin until the needed high
degree of purity is obtained. The pharmaceutical manufacturing of the various insulin
preparations and the crystallization of the finished product come next.
 Next, the biosynthesis of human insulin was used as the model for creating insulin
analogues with different amino acid sequences and time-action properties. The
creation of insulin precursor proteins, post-translational modification, and purification
are all stages that are employed to make insulin analogues. Several insulin analogues
are created by changing the encoded gene sequence. Fast-acting (rapid-acting)
analogs readily absorb from the site of subcutaneous (sc) injection within 10 to 15
minutes (lispro, aspart, glulisine insulin). Long-acting analogues maintain basal insulin
levels for longer than 24 hours (insulin glargine, insulin detemir). NPH insulin (Humulin N,
Novolin N, Insuman Basal) is a suspension of human insulin in protamine with a length of
action of 16 to 20 hours and a clear peak of action, in contrast to insulin glargine, which
has a duration of action of more than 24 hours and a flat time-action profile activity
(intermediate acting).

Human insulin biosimilars are created to closely resemble the reference insulin
products. The European approval process has been developed and is being put into
practice, notwithstanding the possibility that different nations' regulatory frameworks for
these biosimilar insulins would differ (WC500144124). In order to prove their safety and
effectiveness, biosimilar insulins must overcome a number of regulatory obstacles
related to bioequivalence and clinical investigations.

Recombinant human insulin has been the standard for a long time. The
formulations for lunchtime injection (soluble), basic support (NPH), and traditional
therapy (pre-mix combination) are well known and available in a variety of useful forms
(disposable and reusable insulin pens). Based on availability and affordability, human
insulin formulations are frequently chosen as the best options for treating type 1
diabetes. Even though there are a number of first therapies for type 2 diabetes, when
other glycemic control methods fail, early insulin therapy is always the best choice. In
many countries, pricing and reimbursement are important challenges. The economies
of scale involved in the pharmaceutical processing of formulations and the production
of human insulin must be taken into consideration. Both conventional human insulin and
NPH insulin are still used in many countries. The affordability of treatment has a big
impact on the availability of several insulin analogues, each of which has advantages
including quick absorption and long-lasting action. Preparations containing
recombinant human insulin for the treatment of diabetes have a well-established
record of efficacy; in countries where cost is still a significant determining factor, this is
the main area of concern.

References:

Sandow J, Landgraf W, Becker R, Seipke G. Equivalent Recombinant Human Insulin

Preparations and their Place in Therapy. Eur Endocrinol. 2015 Apr;11(1):10-16. doi:
10.17925/EE.2015.11.01.10. Epub 2015 Apr 11. PMID: 29632560; PMCID: PMC5819055.

The History of a Wonderful Thing We Call Insulin | ADA. (n.d.). Retrieved September 24,
2022, from https://diabetes.org/blog/history-wonderful-thing-we-call-
insulin#:%7E:text=The%20first%20genetically%20engineered%2C%20synthetic,under%20t
he%20brand%20name%20Humulin.