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The article discusses contributions of insulin to science in medicine. Topics include convenience of use and the achievable magnitude of glycaemic control alongside a low risk of hypoglycaemia; and pivotal advance made it possible to produce human insulin in unlimited quantities and paved the way for engineering in insulin analogues.

The discovery of insulin in 1921 and the progress achieved in the ensuing century highlight the promise and challenge of biochemically modifying the molecule to achieve optimization of its delivery and therapeutic efficacy. Normal endogenous insulin secretion consists of a highly orchestrated physiologic loop wherein multiple metabolic signals trigger the pancreatic β cells to secrete the precise amount of insulin into the portal system required to maintain euglycemia. Accordingly, in the treatment of diabetes, attempting to replicate this complex physiology with exogenous insulin therapy given subcutaneously presents a clinical challenge. In this context, recombinant DNA-based technology has enabled the development of insulin analogs that have been specifically designed to confer advantageous pharmacodynamic features that can better mimic endogenous insulin secretion. In this review, we discuss the development of the most widely available insulin preparations and provide evidence-based insight into their use in clinical practice. The discovery of insulin in 1921 and the progress achieved in the ensuing century highlight the promise and challenge of biochemically modifying the molecule to achieve optimization of its delivery and therapeutic efficacy. In this review, Kramer et al. discuss the development of the most widely available insulin preparations and provide evidence-based insight into their use in clinical practice. [ABSTRACT FROM AUTHOR]

The purpose of this article is to describe the research of Nicolae Constantin Paulescu and to emphasize his role in the discovery of insulin. Methods: We made a thorough review of the literature and research in the Romanian Academy Archive in order to find adequate references. Results: In 1912 N.C. Paulescu analysed the clinical and biochemical alterations in diabetic patients and in dogs after performing a pancreatectomy, that apart hyperglycemia and glycosuria (carbohydrate metabolism), had noted also changes in lipid and protein metabolism. In 1916 he started the experiments with a pancreas extract obtained by his original method, that was injected intravenously to the diabetic dogs. The results of his first experiments showed: "The pancreatic extract injected into a peripheral vein produce: 1) A diminution and even a temporary suppression of diabetic hyperglycemia, which may be replaced by hypoglycemia; 2) A diminution or even temporary suppression of glycosuria; 3) A diminution of blood urea; 4) A diminution of urinary urea. In other words, the intravenous injection of the pancreatic extract has as effect the disappearance of diabetic symptoms. The attenuation of the diabetic syndrome begins immediately after the injection. It reaches a maximum after 2 hours,- and it lasts for about 12 hours". He concluded as such: "This discovery,- which sheds a bright light over the pathogenesis of diabetes gives us also the key for the treatment of this syndrome". In 1921, Paulescu had published extensively his data in two outstanding French journals 8 months before the first publication of Banting and Best from February 1922. It is clear that insulin has been discovered in Europe. Conclusion: Paulescu thought that a new hormone - Pancreine, that he discovered is the key element in the treatment of diabetes, but his outstanding research was unfairly neglected. [ABSTRACT FROM AUTHOR]

Since the discovery of insulin, continuous developments of this peptide have led to better management of diabetes mellitus, thus leading to a decrease in diabetes-related mortality. Despite these developments, we have seen an increase in diabetes cases, which has further necessitated more innovative methods for diabetes management. The subcutaneous administration of insulin remains the mainstay therapy for type 1 diabetes mellitus. However, despite the availability of insulin analogues with improved pharmacokinetics, challenges with conventional administration exist. The challenges associated with insulin injections include hypoglycaemic episodes, needle phobia, and injection-site inflammation, which all have been reported to reduce patient compliance. Ongoing research on diabetes management strives to develop therapies that provide improved glycaemic control with minimal side effects. In part, for these reasons, we have seen an increase in the search and development of alternative insulin delivery systems that are envisaged to circumvent the shortfalls associated with the conventional administration route. Several alternative drug delivery systems, such as oral, pulmonary, buccal, nasal, and transdermal, have been explored in the last century. These efforts have not been without victory, as we have seen the emergence of pulmonary (Exubera and Afrezza) and buccal insulin delivery systems licenced for therapeutic use. Despite the success seen in these two systems, their marketability and popularity have been severely compromised due to reported safety concerns. Although oral insulin delivery has always shown promise in the past decades; however, it was only limited to preclinical trials. The main challenge associated with this delivery route is poor bioavailability, which necessitates high insulin concentration to be administered. Due to recent developments, oral insulin has reached phase 3 clinical trials. It is believed that patients would prefer oral insulin as their preference is often observed for oral antidiabetics over injected ones. In the last decade, transdermal insulin has also gained interest, where delivery of insulin with a concomitant reduction in blood glucose concentration has been demonstrated in vivo. However, at present, there are no clinical studies that have reported the efficacy of transdermal insulin administration. With technological advancement, there is a potential to develop yet another insulin delivery system that would likely enter the markets. As these novel delivery systems have been found to be effective, emerging competing products should be welcome and appreciated., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The discovery of insulin in 1921 – due to the efforts of the Canadian research team based in Toronto – has been a landmark achievement in the history of medicine. Lives of people with diabetes were changed forever, considering that in the pre-insulin era this was a deadly condition. Insulin, right after its discovery, became the first hormone to be purified for human use, the first to be unraveled in its amino acid sequence and to be synthetized by DNA-recombinant technique, the first to be modified in its amino acid sequence to modify its duration of action. As such the discovery of insulin represents a pivotal point in medical history. Since the early days of its production, insulin has been improved in its pharmacokinetic and pharmacodynamic properties in the attempt to faithfully reproduce diurnal physiologic plasma insulin fluctuations. The evolution of insulin molecule has been paralleled by evolution in the way the hormone is administered. Once-weekly insulins will be available soon, and glucose-responsive "smart" insulins start showing their potential in early clinical studies. The first century of insulin as therapy was marked by relentless search for better formulations, a search that has not stopped yet. New technologies may have, indeed, the potential to provide further improvement of safety and efficacy of insulin therapy and, therefore, contribute to improvement of the quality of life of people with diabetes. • Before insulin, type 1 diabetes was a fatal disease. • The discovery of insulin in 1921 contributed to a better understanding of diabetes. • Since its discovery, insulin preparations have continued to evolve. • New delivery systems and alternative routes of administration have been developed. • New insulins, including weekly, oral and smart insulins, may soon be available. [ABSTRACT FROM AUTHOR]

Insulin discovery has been always related with Banting and Macleod, but the historic true is another. A huge number of researchers set the bases for the discovery that by cientific merit corresponded to rumanian professor Nicolae Constantine Paulescu, whom, for different reasons was denied the Nobel Prize. The objective of this paper is to recognize the life achievements and cientific contributions of doctor Paulescu and the circumstances that he experienced in relation to the Medicine Nobel Prize of 1923 by the insulin discovery. [ABSTRACT FROM AUTHOR]

The isolation and purification of insulin nearly 100 years ago has been one of the most ground-breaking discoveries in the history of medicine. Subsequent determination of the specific structure of human insulin has permitted further developments and modifications of the formulations of insulin to allow improved quality of care and quality of life for patients with diabetes. In this paper, we will review insulin structure and biosynthesis, treatment and prognosis of type 1 diabetes prior to insulin therapy, experimentation leading to the discovery of insulin, and the first patients to be treated with insulin., (Copyright© of YS Medical Media ltd.)