Proteomic Changes to the Updated Discovery of Engineered Insulin and Its Analogs: Pros and Cons (original) (raw)

Recombinant Human Insulins – Clinical Efficacy and Safety in Diabetes Therapy

European Endocrinology

Insulin replacement therapy is the standard of care for patients with type 1 and advanced type 2 diabetes mellitus. Porcine and bovine pancreatic tissue was the source of the hormone for many years, followed by semisynthetic human insulin obtained by modification of animal insulin. With the development of recombinant DNA technology, recombinant (biosynthetic) human insulin became available in large amounts by biosynthesis in microorganisms (Escherichia coli, yeast) providing reliable supplies of the hormone worldwide at affordable costs. The purity and pharmaceutical quality of recombinant human insulin was demonstrated to be superior to animal and semisynthetic insulin and patients with diabetes could be safely and effectively transferred from animal or semisynthetic human insulin to recombinant human insulin with no change expected in insulin dose. The decision for change remains a clinical objective, follow-up after any change of insulin product is recommended to confirm clinical...

Human Insulin: History, Recent Advances, and Expression Systems for Mass Production

Biomedical Research and Therapy, 2021

The significant rise in the number of diabetic patients worldwide, as well as the development of new insulin delivery techniques such as inhalation or oral administration which require higher dosages, are expected to increase the demand for recombinant insulin. Current manufacturing technologies will be unable to fulfill the rising demand for inexpensive insulin due to their production capacity limitations and high production costs. Production of therapeutic recombinant insulin requires a suitable host organism with adequate post-translational modification and refolding machinery. E. coli and S. cerevisiae have been used extensively to make recombinant human insulin for medicinal applications. However, transgenic plants are particularly appealing expression systems as they can be used to synthesize huge amounts of insulin for human medicinal purposes. Plant-based expression systems have the potential for high-capacity insulin synthesis at a minimal cost. The significant production of biologically active proinsulin in seeds or leaves with long-term stability provides a low-cost technique to develop proinsulin for both injectable and oral administration. Recently, stem cell therapy is being utilized for the treatment of diabetes, as these cells are capable of differentiating into insulin producing c ells. With the advancement of regenerative medicine research for different chronic diseases, treatment for type 1 diabetes mellitus has been reported. The current review concentrates on several biotechnological attributes applied to the rapid and mass synthesis of biologically active insulin and its analogs in microbes, various types of stem cells and transgenic crops.

Insulin's 85th anniversary—An enduring medical miracle

Diabetes Research and Clinical Practice, 2007

In 1922, the discovery of insulin led to a revolution in diabetes management. Since then, many improvements have been made to insulin preparations: early preparations of bovine and porcine insulins were purified and their duration of action prolonged, giving rise to the introduction of Neutral Protamine Hagedorn (NPH) insulin and monocomponent insulins. Then, with the advances in genetic engineering in the 1980s, it became possible to produce recombinant human insulin. Nowadays, modern molecular biology techniques enable the production of insulin analogues, which have several advantages over human insulin preparations including a reduced risk of hypoglycaemia. Insulin delivery is still predominantly via subcutaneous injections, but alternative routes of insulin administration are being investigated. Pulmonary delivery has emerged as the most feasible option thus far but oral delivery is an ultimate goal, although basic problems of insulin stability in the gut and absorption from the gastrointestinal tract still need to be resolved. The availability of a true artificial pancreas by means of a closed-loop system, linking continuous glucose monitoring with insulin-pump technology, would also constitute a significant advance, but major technological problems still need to be overcome.

Industrial Production of Insulin by Genetically Modified Organism

Asian Journal of Science and Applied Technology

Insulin is a hormone secreted from the β cells of the islets of Langerhans, a specific group of cells in the pancreas. Life would not exist without insulin. In order to utilize the glucose (energy) found within the carbohydrate-laden foods we consume, insulin must be present to facilitate its (glucose) absorption. The rapid increase in the number of diabetic patients globally and exploration of alternate insulin delivery methods such as inhalation or oral route that rely on higher doses, is bound to escalate the demand for recombinant insulin in near future. Recombinant human insulin has been produced predominantly using E. coli (Escherichia coli)and Saccharomyces cerevisiae (a species of yeast) for therapeutic use in human. Current manufacturing technologies would be unable to meet the growing demand of affordable insulin due to limitation in production capacity and high production cost. Insulin is one of the most important drugs in medical science therefore it is important to have...

Protein engineering of insulin: Two novel fast-acting insulins [B16Ala]insulin and [B26Ala]insulin

Science in China Series C, 2003

Blood glucose lowering assay proved that [B16Ala]insulin and [B26Ala]insulin exhibit potency of acute blood glucose lowering in normal pigs, which demonstrates that they are fastacting insulin. Single-chain precursor of [B16Ala]insulin and [B26Ala]insulin is [B16Ala]PIP and [B26Ala]PIP, respectively, which are suitable for gene expression. Secretory expression level of the precursors in methylotrophic yeast Pichia pastoris was quite high, 650 mg/L and 130 mg/L, respectively. In vivo biological assay showed that the two fast-acting insulins have full or nearly full biological activity. So both [B16Ala]insulin and [B26Ala]insulin can be well developed as fast-acting insulin for clinic use.

Equivalent Recombinant Human Insulin Preparations and their Place in Therapy

European Endocrinology, 2014

Recombinant human insulin was one of the first products of biotechnology. It was developed in response to the need for a consistent and sufficient worldwide supply. Recombinant human insulin replaced the animal insulins and semisynthetic insulins obtained by modification of animal insulins. Bioequivalence studies were required for regulatory approval. Three reference products were independently established during these procedures: Humulin® (Eli Lilly and Co), Novolin® (NovoNordisk) and Insuman® (Sanofi). Numerous brand names have been used during the commercial development of recombinant human insulin formulations. In this review, three current brand names are used for consistent identification. Human insulin for Humulin and Insuman are produced by fermentation in bacteria (Escherichia coli) and for Novolin in yeast (Saccharomyces cerevisiae). The bioequivalence of recombinant human insulin products was investigated in euglycaemic clamp studies. An overview of such bioequivalence st...

Insulin gene structure and function: a review of studies using recombinant DNA methodology

Diabetes Care, 1984

This review focuses on recent advances in molecular biology as they pertain to the insulin gene and diabetes mellitus. The structure of the human insulin gene is examined, and factors related to its normal functioning in the beta cells of the pancreas are explored. DNA polymorphisms near the insulin locus and their relationship with certain types of diabetes are considered, as are recently characterized human insulin gene mutations. Events in animal models for diabetes that reflect altered insulin gene expression are discussed and the potential application of gene therapy in human diabetes is examined. Recombinant DNA methodology holds great promise as a tool for providing better understanding of the causes of diabetes and potential curative treatment, DIABETES CARE 1984; 7:386-94.

Insulin Past, Present, and Future: 100 Years from Leonard Thompson

Diabetology, 2022

Before the discovery of insulin and the critical role of the pancreas vis-à-vis diabetes mellitus pathophysiology, childhood diabetes or what we now call type 1 or autoimmune diabetes mellitus was almost universally fatal. In limited-resource countries (LRC) around the world, this remains sadly true because of the expense and unavailability of medical care, medical information, and/or medications. In 1889, Minkowski and Mering identified the pancreas as the likely source of the problem in pancreatectomized dog experiments, and Langerhans, working with Virchow, identified the islands of pancreatic tissue now named after Langerhans as the likely source of the problem. Prior to that, Cawley, Boucherdat, Zuelzer, Gley, de Meyer, Schafer, Scott, Kleiner, and Paulescu all worked on this problem with varying results until Banting, Best, MacLeod, and Collip in Toronto in 1921 successfully treated pancreatectomized dogs with an alcohol-based pancreatic extract and then were the first to do t...

Recombinant Human Insulin in Global Diabetes Management – Focus on Clinical Efficacy

European Endocrinology

Biosynthetic human insulin and insulin analogues are the mainstay of insulin therapy for both type 1 and type 2 diabetes although access to human insulin at affordable prices remains a global issue. The world is experiencing an exponential rise in the prevalence of diabetes presenting an urgent need to establish effective diabetes therapy in countries burdened by inadequate health care budgets, malnutrition and infectious diseases. Recombinant human insulin has replaced animal insulins and animal-based semisynthetic human insulin thereby available in sufficient quantities and at affordable prices able to provide global access to insulin therapy. In many patients, analog insulins can offer additional clinical benefit, although at a considerably higher price thus severely restricting availability in low income countries. The approval process for recombinant human insulins (i.e. biosimilars) and analogue insulins is highly variable in the developing countries in contrast to Europe and ...