Strengthening The Chemical Structure Of Insulin Can Lead To Future Non-perishable Insulin Pills
A team of Australian chemistry students have strengthened the chemical bonds of insulin to make it stable even at warm temperatures -- a breakthrough that could simplify diabetes management. The finding could shed light on how insulin works, and eventually lead to insulin pills, rather than injections or pumps. Insulin needs to be kept cold because it is made of weak chemical bonds that degrade at temperatures above 40 degrees Fahrenheit, making it inactive. But using a series of chemical reactions, the research team, comprised of students from Monash University in Australia, replaced the unstable bonds with stronger, carbon-based ones. Play Video Play Loaded: 0% Progress: 0% Remaining Time -0:00 This is a modal window. Foreground --- White Black Red Green Blue Yellow Magenta Cyan --- Opaque Semi-Opaque Background --- White Black Red Green Blue Yellow Magenta Cyan --- Opaque Semi-Transparent Transparent Window --- White Black Red Green Blue Yellow Magenta Cyan --- Opaque Semi-Transparent Transparent Font Size 50% 75% 100% 125% 150% 175% 200% 300% 400% Text Edge Style None Raised Depressed Uniform Dropshadow Font Family Default Monospace Serif Proportional Serif Monospace Sans-Serif Proportional Sans-Serif Casual Script Small Caps Defaults Done The stronger bonds stabilize the insulin's two protein chains without interfering with its natural activity, according to a story about the findings at SciGuru. The so-called "dicarba" insulins were stable at room temperature for several years, SciGuru says. Even more promising is that the findings provide insight into how insulin works. People with Type 1 and Type 2 diabetes do not produce enough insulin, whether it's the result of an auto-immune disorder that stops producing it entirely (Type 1) or a condition brought on by othe Continue reading >>
How Insulin Is Made - Material, Manufacture, History, Used, Parts, Components, Structure, Steps, Product
Background Insulin is a hormone that regulates the amount of glucose (sugar) in the blood and is required for the body to function normally. Insulin is produced by cells in the pancreas, called the islets of Langerhans. These cells continuously release a small amount of insulin into the body, but they release surges of the hormone in response to a rise in the blood glucose level. Certain cells in the body change the food ingested into energy, or blood glucose, that cells can use. Every time a person eats, the blood glucose rises. Raised blood glucose triggers the cells in the islets of Langerhans to release the necessary amount of insulin. Insulin allows the blood glucose to be transported from the blood into the cells. Cells have an outer wall, called a membrane, that controls what enters and exits the cell. Researchers do not yet know exactly how insulin works, but they do know insulin binds to receptors on the cell's membrane. This activates a set of transport molecules so that glucose and proteins can enter the cell. The cells can then use the glucose as energy to carry out its functions. Once transported into the cell, the blood glucose level is returned to normal within hours. Without insulin, the blood glucose builds up in the blood and the cells are starved of their energy source. Some of the symptoms that may occur include fatigue, constant infections, blurred eye sight, numbness, tingling in the hands or legs, increased thirst, and slowed healing of bruises or cuts. The cells will begin to use fat, the energy source stored for emergencies. When this happens for too long a time the body produces ketones, chemicals produced by the liver. Ketones can poison and kill cells if they build up in the body over an extended period of time. This can lead to serious illne Continue reading >>
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Insulin
Insulin is a hormone, which contriutes to cell signalling. Its main function is the regulation of blood sugar levels, by causing the liver and muscles to increase uptake of glucose [1]. Insulin is produced from a single gene which codes for the peptide proinsulin; a precursor molecule. Mutations in this gene can result in a faulty protein; causing type 1 diabetes or a possible predisposition to type 2 diabetes [2][3]. Insulin regulates the blood glucose levels in different ways. It enhances the glucose transport at a cellular level by stimulation of the glucose transporter (GLUT) family. Insulin also has an effect on gene expression which is up or down regulated in the homeostasis process to maintain the optimum blood glucose levels. Insulin is released by the beta-cells (Islets of Langerhans) of the pancreas. Contents [hide] 1 History 2 Insulin stimulates glycogen synthesis 3 Origin of structure 4 Forming the structure of Insulin 5 Physical properties 6 Using recombinant DNA technology to produce active insulin molecules 7 References Insulin was first discovered in 1921 by Dr Frederick Banting and Charles Best after removing the pancreas from dogs and cattle[4]. Frederick Sanger's pioneering research led him to discover the amino acid sequence of the insulin in 1953 [5]. Insulin stimulates glycogen synthesis When blood sugar levels are high, insulin binds to a tyrosine kinase receptor. Binding of insulin triggers a phosphorylation cascade, preventing phosphorylation of glycogen synthase as this inactivates it's activity [6]. Insulin acts antagonistically to the hormone glucagon, which acts on glycogen storage in response to low blood sugar levels [7]. This serves as an effective homeostasis mechanism. Origin of structure Insulin (a globular protein) is extracted and pu Continue reading >>
Insulin
Insulin is a small peptide (protein) consisting of fifty-one amino acids synthesized and stored within the pancreas, an organ situated behind the stomach. The protein itself consists of two chains, denoted A and B, linked by disulfide (sulfur-sulfur) bridges between cysteine residues (see Figure 1). Insulin is a hormone, a chemical transported in the blood that controls and regulates the activity of certain cells or organs in the body. When blood sugar levels rise following a meal, the pancreas is stimulated to release insulin into the bloodstream. In order for tissues to absorb glucose from the blood, they must first bind insulin. Glucose metabolism is necessary for cell growth and energy needs associated with cell function. When insulin binds to receptors on cell membranes, glucose transporter proteins are released from within the cell to the surface of the cell membrane. Once on the exterior surface of cells, glucose transporters can carry sugar from the blood into the tissue where it is metabolized. Without insulin, cells cannot absorb glucose and effectively starve. A deficiency in insulin production results in a condition called diabetes mellitus. Approximately 6.2 percent of the population in the United States is affected with diabetes. Type 1 diabetics account for 10 percent of those individuals suffering from diabetes mellitus. It is also known as juvenile diabetes and generally develops in young people, typically between the ages of ten and fifteen years, as a result of an autoimmune disorder. Why the body's immune system turns on itself, attacking and destroying beta cells, the pancreatic cells in which insulin is synthesized, is not clear. The unfortunate consequence is insulin deficiency. The majority of individuals afflicted with diabetes mellitus suffer f Continue reading >>
Frontiers | Landmarks In Insulin Research | Endocrinology
Front. Endocrinol., 22 November 2011 | Colin W. Ward1 and Michael C. Lawrence 1,2* 1 Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia 2 Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia Ever since the discovery of insulin and its role in the regulation of glucose uptake and utilization, there has been great interest in insulin, its structure and the way in which it interacts with its receptor and effects signal transduction. As the 90th anniversary of the discovery of insulin approaches, it is timely to provide an overview of the landmark discoveries relating to the structure and function of this remarkable molecule and its receptor. Frederick Banting made the first public presentation of the discovery of insulin to the Association of American Physicians in 1922 ( Banting et al., 1922 ). The remarkable story of the Toronto group of Banting, Charles Best, James Collip, and John Macleod and their monumental finding is now well documented ( Bliss, 1982 ; Rosenfeld, 2002 ; King, 2003 ). The discovery was followed shortly after by the successful large-scale production of insulin in 1923 by the USA company Eli Lilly, resulting from a collaboration between the Toronto researchers and the companys director of biochemical research George Clowes. This was followed rapidly by the treatment of patients with insulin produced in Copenhagen. August Krogh, a doctor and researcher in metabolic diseases, and his wife Marie, a type II diabetic, had heard about Banting and Bests research while touring the USA in late 1922 and were granted permission to produce insulin in Denmark. On his return to Denmark, Krogh, together with Hans Christian Hagedorn, founded the Nordisk Insulinlaboratorium with the financial support of pharmaci Continue reading >>
Insulin (ox) [
»Insulin is a protein that affects the metabolism of glucose.It is obtained from the pancreas of healthy bovine or porcine animals,or both,used for food by humans.Its potency,calculated on the dried basis,is not less than 26.5USP Insulin Units in each mg;Insulin labeled as purified contains not less than 27.0USP Insulin Units in each mg,calculated on the dried basis.The proinsulin content,determined by a validated method,is not more than 10ppm. NOTE—One USP Insulin Unit is equivalent to 0.0342mg of pure Insulin derived from beef or 0.0345mg of pure Insulin derived from pork. Packaging and storage— Preserve in tight containers.Store,protected from light,in a freezer. Labeling— Label it to indicate the one or more animal species to which it is related,as pork,as beef,or as a mixture of pork and beef.If the Insulin is purified,label it as such. Identification— A: The retention time of the insulin peak in the chromatogram of the Assay preparationcorresponds to the retention time of the appropriate species in the chromatogram of the Identification preparation,as obtained in the Assay.[NOTE—It may be necessary to inject a mixture of Assay preparationand Identification preparation.] B: Proceed as directed for Identificationtest BunderInsulin Human,except to use 1mg of USP Insulin Reference Standard of the appropriate species to prepare the Standard digest solution,to use 1mg of Insulin to prepare the Test digest solution,and to obtain a resolution,R,between digest fragments IIand IIIof not less than 1.9:meets the requirements. Related compounds— Solvent— Dissolve 28.4g of anhydrous sodium sulfate in 1000mLof water.Pipet 2.7mLof phosphoric acid into this solution,adjust,if necessary,with ethanolamine to a pHof 2.3,and mix. Solution A— Prepare a filtered and deg Continue reading >>
Three-dimensional Atomic Structure Of Insulin And Its Relationship To Activity
The three-dimensional structure of the insulin molecule has been determined by single crystal x-ray analysis. The two chains are compactly arranged with the A chain lying above a central helical region of the B chain. From each end of the helix the terminal residues extend as arms, and the A chain is enclosed between these. This limits the A chain to one surface of the molecule. Two surfaces, made up of B chain residues, are nonpolar and are buried by the aggregation of the molecule into a dimer and then into a hexamer. The insulin molecules of the 12,000 molecular weight dimer are related by an approximate twofold axis. Three such dimers can come together and in the presence of zinc ions form the stable 36,000 molecular weight hexamer. The three dimers have identical structures and are related by a threefold axis. The approximate twofold axis of the dimer is perpendicular to this. There is good evidence that insulin is stored in the granule as small crystals of this hexamer. The A chain terminal residues A1 glycine, A5 glutamine, A19 tyrosine and A21 asparagine are on the surface of the molecule. They are invariant and not involved in the aggregation of the molecule. Their deletion affects both the structure and activity of insulin. Substitution at A1 glycine, especially of bulky groups, reduces activity substantially but seems to affect the molecular structure less. In proinsulin the connecting peptide appears to cover these residues. Therefore the surface A chain terminal residues apparently are important to the molecule's activity. Continue reading >>
Insulin - An Overview | Sciencedirect Topics
Insulin is a protein consisting of two polypeptide chains, A chain and B chain, linked together by disulfide bonds. Brian L. Furman, in xPharm: The Comprehensive Pharmacology Reference , 2007 Insulin is normally secreted rapidly from the beta-cells of the pancreatic islets in response to nutrients absorbed after a meal. In type 1 diabetes mellitus, there may be an absolute insulin deficiency as a consequence of autoimmune destruction of the beta-cells. On the other hand, in type 2 diabetes mellitus, insulin secretion is impaired and is inadequate to overcome peripheral insulin resistance. Insulin preparations are used to replace the deficient hormone in the treatment of diabetes, and currently, there is no alternative therapy for type 1 diabetes. Insulin is also to be used in the treatment of type 2 diabetes when this cannot be adequately controlled by orally active antidiabetic drugs. The aim of treatment using insulin is to maintain euglycemia (a plasma glucose level of 47 mmol/L) without causing hypoglycemia. There is much evidence that good control in both type 1 and type 2 diabetes will reduce the development of long-term microvascular and neuropathic complications of the disorder DCCT Research Group (1993), UK Prospective Diabetes Study Group (1998). However, good control is difficult to achieve because of the difficulty of administering insulin in a way that mimics physiological insulin secretion, with rapid peaks during and immediately after a meal and low, basal concentrations between meals. Insulin preparations are now largely based on human insulin prepared by enzymic modification of porcine insulin [human insulin (emp)], by chemical combination of the A and B chains produced using bacteria genetically modified by recombinant DNA technology [human insulin (c Continue reading >>
What Are The Possible Side Effects Of Insulin Glulisine (apidra, Apidra Opticlik Cartridge, Apidra Solostar Pen)?
APIDRA (insulin glulisine [rDNA origin]) Solution for Injection DESCRIPTION APIDRA® (insulin glulisine [rDNA origin] injection) is a rapid-acting human insulin analog used to lower blood glucose. Insulin glulisine is produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli (K12). Insulin glulisine differs from human insulin in that the amino acid asparagine at position B3 is replaced by lysine and the lysine in position B29 is replaced by glutamic acid. Chemically, insulin glulisine is 3B-lysine29B-glutamic acid-human insulin, has the empirical formula C258H384N64O78S6 and a molecular weight of 5823 and has the following structural formula: APIDRA is a sterile, aqueous, clear, and colorless solution. Each milliliter of APIDRA contains 100 units (3.49 mg) insulin glulisine, 3.15 mg metacresol, 6 mg tromethamine, 5 mg sodium chloride, 0.01 mg polysorbate 20, and water for injection. APIDRA has a pH of approximately 7.3. The pH is adjusted by addition of aqueous solutions of hydrochloric acid and/or sodium hydroxide. font size A A A Type 2 diabetes: See Diabetes, type 2. Source: MedTerms™ Medical Dictionary Continue reading >>
Insulin
With a speed no longer seen in drug discovery and development, insulin was isolated for the first time in 1921 from animal sources and commercialized within 12 months. Decades later, it took just four years for developers to move from expressing recombinant insulin in bacteria to launching the world's first biotechnology drug product. Scientists Frederick G. Banting and Charles H. Best, working in a lab provided by John J. R. MacLeod at the University of Toronto, isolated the polypeptide hormone and began testing it in dogs. By 1922, with the help of James B. Collip and pharmaceutical company partners, the researchers could purify and produce animal-based insulin in larger quantities. Insulin is produced by beta cells in the pancreas and is the most important hormone in the body to regulate blood glucose levels. A partial or complete lack of insulin causes diabetes, which, untreated, is often fatal by the teenage years. The World Health Organization reports that an estimated 177 million people worldwide have diabetes. Although not a cure, insulin injections have been the standard treatment since 1924. Before insulin was discovered, diabetes was managed through diet, which allowed patients to survive, but generally for just a few years after diagnosis. Remarkable medical results were achieved with the first insulin injections. Doctors finally had a means to offer patients a nearly normal quality of life, and it quickly became necessary to increase insulin production. The Toronto scientists had trouble, however, with consistently isolating and purifying the drug. Connaught Laboratories in Canada, now part of Sanofi-Aventis, assisted, and Eli Lilly & Co. proposed developing large-scale production methods. The university initially rebuffed offers from Lilly, but an agreemen Continue reading >>
Structural Biochemistry/protein Function/insulin
Insulin is a hormone secreted by the pancreas that regulates glucose levels in the blood. Without insulin, cells cannot use the energy from glucose to carry out functions within the body. Insulin was first discovered in 1921 by Frederick Grant Banting and Charles Best from extracted substances from the pancreas of dogs in their laboratory. The material was then used to keep diabetic dogs alive, and then used in 1922 on a 14 year old diabetic boy. The FDA approved insulin in 1939. In 1966 insulin was synthesized by Michael Katsoyannis in his laboratory, which marked the first complete hormone to be successfully synthesized. Synthetic insulin is used as a drug to treat diabetes, and the current forms on the market include insulin from bovine and porcine pancreases, but the most widely used is a form made from recombinant human insulin. Insulin is made in the pancreas by beta cells. After the body takes in food, these beta cells release insulin, which enables cells in the liver, muscles and fat tissues to take up glucose and either store it as glycogen or allow blood to transfer it to organs in the body for use as an energy source. This process stops the use of fat as a source of energy. When glucose levels are elevated in the blood, insulin is produced at higher rates by the pancreas in order to maintain normal sugar concentrations in the blood. Without insulin, the body cannot process glucose effectively and glucose begins to build up in the blood stream instead of being transported to different cells . In contrast with elevated levels of glucose in the blood, when there is a deficit of glucose available to the body, alpha cells in the pancreas release glucagon, a hormone that causes the liver to convert stored glycogen into usable glucose which is then released into the Continue reading >>
Insulin Peptide Hormone, Chemical Structure. Important Drug In T
Insulin peptide hormone, chemical structure. Important drug in treatment of diabetes. Shown in het hexameric form, bound to zinc ions. Atoms are represented as spheres. Coloring: purple A chains, blue B chains. Continue reading >>
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Pursuit Of A Perfect Insulin
Insulin remains indispensable in the treatment of diabetes, but its use is hampered by its narrow therapeutic index. Although advances in peptide chemistry and recombinant DNA-based macromolecule synthesis have enabled the synthesis of structurally optimized insulin analogues, the growing epidemics of obesity and diabetes have emphasized the need for diabetes therapies that are more efficacious, safe and convenient. Accordingly, a broad set of drug candidates, targeting hyperglycaemia plus other disease abnormalities, is now progressing through the clinic. The development of an insulin therapy that is responsive to glucose concentration remains an ultimate goal, with initial prototypes now reaching the proof-of-concept stage. Simultaneously, the first alternatives to injectable delivery have progressed to registration. Home, P. et al. Insulin therapy in people with type 2 diabetes: opportunities and challenges? Diabetes Care 37, 1499–1508 (2014). A panel of specialists provides guidelines to initiating insulin therapy in the context of recent findings and novel treatment options. Gough, S. C. et al. One-year efficacy and safety of a fixed combination of insulin degludec and liraglutide in patients with type 2 diabetes: results of a 26-week extension to a 26-week main trial. Diabetes Obes. Metab. 17, 965–973 (2015). This extended clinical study underscores the benefits of combination therapy of insulin with GLP1 analogues. Vora, J. & Heise, T. Variability of glucose cowering effect as a limiting factor in optimizing basal insulin therapy: a review. Diabetes Obes. Metab. 15, 701–712 (2013). The identification of inter-and intra-patient variability as the major issue of the current insulin therapies and establishing it as a primary consideration for future treatments Continue reading >>
A Note On The Structure Of Insulin
View Affiliations © 1948 American Institute of Physics. View Affiliations 2. W. J. Taylor and R. S. Pitzer, J. Research Nat. Bur. Stand. 38, 1 (1947); Google Scholar G. Herzberg, Infrared and Raman Spectra of Polyatomic Molecules (D. Van Nostrand Company, Inc., New York, 1945). Google ScholarCrossref, CAS © 1948 American Institute of Physics. View Affiliations © 1948 American Institute of Physics. View Affiliations © 1948 American Institute of Physics. Continue reading >>
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Structure Of Insulin
Insulin is composed of two peptide chains referred to as the A chain and B chain. A and B chains are linked together by two disulfide bonds, and an additional disulfide is formed within the A chain. In most species, the A chain consists of 21 amino acids and the B chain of 30 amino acids. Although the amino acid sequence of insulin varies among species, certain segments of the molecule are highly conserved, including the positions of the three disulfide bonds, both ends of the A chain and the C-terminal residues of the B chain. These similarities in the amino acid sequence of insulin lead to a three dimensional conformation of insulin that is very similar among species, and insulin from one animal is very likely biologically active in other species. Indeed, pig insulin has been widely used to treat human patients. Insulin molecules have a tendency to form dimers in solution due to hydrogen-bonding between the C-termini of B chains. Additionally, in the presence of zinc ions, insulin dimers associate into hexamers. These interactions have important clinical ramifications. Monomers and dimers readily diffuse into blood, whereas hexamers diffuse poorly. Hence, absorption of insulin preparations containing a high proportion of hexamers is delayed and somewhat slow. This phenomenon, among others, has stimulated development of a number of recombinant insulin analogs. The first of these molecules to be marketed - called insulin lispro - is engineered such that lysine and proline residues on the C-terminal end of the B chain are reversed; this modification does not alter receptor binding, but minimizes the tendency to form dimers and hexamers. Send comments to [email protected] Continue reading >>
