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 >>
Tweet Human insulin is the name which describes synthetic insulin which is laboratory grown to mimic the insulin in humans. Human insulin was developed through the 1960s and 1970s and approved for pharmaceutical use in 1982. Before human insulin was developed animal insulin, usually a purified form of porcine (pork) insulin, was used. How is human insulin produced? Human insulin is laboratory created by growing insulin proteins within E-coli bacteria (Escherichia coli). What types of human insulin are available? Human insulin is available in two forms, a short acting (regular) form and an intermediate acting (NPH) form. NPH (Neutral Protamine Hagedorn) insulin, also known as isophane insulin, is a suspension meaning that the insulin vial should be rolled or repeatedly turned upside down to ensure the solution is uniformly cloudy. Some examples of human insulin: Regular (short acting): Humulin S, Actrapid, Insuman Rapid NPH (intermediate acting): Humulin I, Insuman basal, Insulatard Premixed human insulins: Humulin M2, M3 and M5, Insuman Comb 15, 25 and 50 What are premixed human insulins? Premixed insulins consist of a mix of regular and NPH insulin. The premixed insulins are available in a number of different ratios of mixing. For example Humulin M3 is a mix of 30% short acting to 70% intermediate whereas Humulin M5 is made up of 50% of both short and intermediate acting. In recent years there has been a trend to replace human insulins with newer premixed analogue insulins. How quickly do human insulins act? Short acting (regular) insulin starts to act from about 30 minutes after injecting, with their peak action occurring between 2 and 3 hours after injecting. The duration is up to 10 hours. Intermediate acting (NPH) insulin takes about 2 to 4 hours to start acting, h Continue reading >>
Diabetics Not Told Of Insulin Risk
Evidence that thousands of diabetics in Britain may have suffered a deterioration in their health from synthetic insulin has been withheld by the British Diabetics Association, whose role is to advise patients and to protect their interests. The evidence was contained in a report, commissioned by the association and completed six years ago, which highlighted dangers faced by about 10 per cent of the 150,000 diabetics who had been switched from the traditional animal-derived insulin to synthetic human insulin. Some of those adversely affected began, without warning, to go into comas, known as hypoglycaemic episodes or 'hypos'. Some suffered severe injuries, a few crashed their cars, and others believed they would have died had they not been rescued as they lay unconscious. An estimated 15,000 people may still suffer because they are injecting themselves twice a day with insulin that may not suit them. Many doctors are unaware of the problem, or have failed to put their patients back on animal insulin because they do not know it is still available. The association says it did not publish the report because it was 'too alarmist'. Simon O'Neill, head of diabetes care services, said the association agreed that up to 20 per cent of insulin injectors preferred animal insulin and had experienced difficulties with synthetic insulin. He added that the association had published a report, The Insulin Debate, which dealt with the issues, continued to keep members informed of developments, and campaigned to keep animal insulin available to sufferers. Synthetic insulin is manufactured by two major drug companies, the Danish Novo Nordisk and US giant Elli Lilly. Neither company accepts that the synthetic version has negative effects. The report was compiled following 3,000 letters of c Continue reading >>
First Successful Laboratory Production Of Human Insulin Announced
South San Francisco, Calif. -- September 6, 1978 -- Genentech, Inc. and City of Hope National Medical Center, a private research institution and hospital in Duarte, California today announced the successful laboratory production of human insulin using recombinant DNA technology. Insulin is a protein hormone produced in the pancreas and used in the metabolism of sugar and other carbohydrates. The synthesis of human insulin was done using a process similar to the fermentation process used to make antibiotics. The achievement may be the most significant advance in the treatment of diabetes since the development of animal insulin for human use in the 1920's. The insulin synthesis is the first laboratory production DNA technology. Recombinant DNA is the technique of combining the genes of different organisms to form a hybrid molecule. DNA (deoxyribonucleic acid), the substances genes are composed of, contains the chemical record in which genetic information is encoded. Scientists at Genentech and City of Hope inserted synthetic genes carrying the genetic code for human insulin, along with the necessary control mechanism, into an E. coli bacterial strain which is a laboratory derivative of a common bacteria found in the human intestine. Once inside the bacteria, the genes were "switched-on" by the bacteria to translate the code into either "A" or "B" protein chains found in insulin. The separate chains were then joined to construct complete insulin molecules. The development of genetically engineered human insulin was funded by Genentech. However, the work was a cooperative effort between Genentech and City of Hope. The synthesis of human insulin gene was accomplished by four scientists at City of Hope Medical Center led by Roberto Crea, Ph.D., and Keichi Itakura, Ph.D. Scien Continue reading >>
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History Of Insulin
Dr Frederick Banting and medical student Charles Best perform experiments on the pancreases of dogs in Toronto, Canada. Professor John Macleod provides Banting and Best with a laboratory to carry out the experiments. When the pancreases are removed the dogs showed symptoms of diabetes. The pancreas was then sliced and ground up into an injectable extract. This is injected a few times a day which helped the dogs to regain health. Given the early success, Macleod wants to see more evidence that the procedure worked and provides pancreases from cows to make the extract which is named ‘insulin’. Bertram Collip, a biochemist, joins the research team to provide help with purifying the insulin to be used for testing on humans. Banting and Best clearly had confidence in the insulin as they were the first humans to test the insulin by injecting themselves with it which caused them to experience weakness and dizziness, signs of hypoglycemia. After the group had experimented enough to gain an understanding of the required doses and how best to treat hypoglycemia, their insulin is deemed ready to be tried on patients. Tweet Type 2 diabetes mellitus is a metabolic disorder that results in hyperglycemia (high blood glucose levels) due to the body: Being ineffective at using the insulin it has produced; also known as insulin resistance and/or Being unable to produce enough insulin Type 2 diabetes is characterised by the body being unable to metabolise glucose (a simple sugar). This leads to high levels of blood glucose which over time may damage the organs of the body. From this, it can be understood that for someone with diabetes something that is food for ordinary people can become a sort of metabolic poison. This is why people with diabetes are advised to avoid sources of dieta Continue reading >>
How Insulin Is Made Using Bacteria
Website Search Description: Synthetic human insulin was the first golden molecule of the biotech industry and the direct result of recombinant DNA technology. Currently, millions of diabetics worldwide use synthetic insulin to regulate their blood sugar levels. Synthetic insulin is made in both bacteria and yeast. Keywords: recombinant dna technology,blood sugar levels,human insulin,biotech industry,diabetics,molecule,bacteria,yeast Synthetic human insulin was the first golden molecule of the biotech industry and the direct result of recombinant DNA technology. Currently, millions of diabetics worldwide use synthetic insulin to regulate their blood sugar levels. Synthetic insulin i Continue reading >>
The Great Debate: Natural Animal Or Artificial ‘human’ Insulin?
Home » Diabetic Commonsense » The Great Debate: Natural Animal or Artificial ‘Human’ Insulin? Diabetes commonsense The Great Debate: Natural Animal or Artificial ‘Human’ Insulin? Progress towards becoming a well-balanced diabetic is not helped by the wide range and increasing choice of insulins being put on the market. Is this complication really necessary? Over forty varieties of insulin (3) are advertised and none of them would be on the shelves unless manufacturers could make a profit by selling them. Commonsense tells me to complain loudly about having to find my way and make the right choices through the insulin maze. It does not matter if we select the wrong toothpaste or cat food, but insulin is different. The diabetic community cannot survive without this life-saving drug. We therefore form a captive market and, as any economist will tell you, this creates a perfect opportunity for experts to manipulate and exploit us. Have our gurus the time or inclination to guide us through this jungle of short, medium, long-term and mixed insulins? Do they explain the scientific jargon and help us make a free and informed choice? In this search for the right insulin, newly-diagnosed diabetics, handcuffed by ignorance and fear, are particularly vulnerable. No way can they decide for themselves which insulin to use. They have to be guided by the care team who, in these circumstances, have no option but to take control. Let us hope that sooner rather than later, these fledgling diabetics will be able to fly from the nest and act on their own initiative to make an informed choice of which insulin suits them best. Three clues will help us make up our mind. The first is not to abdicate in favour of the care team or encourage them to steal our melody. The second clue is n Continue reading >>
Why Is Insulin So Expensive In The U.s.?
Dr. Jeremy Greene sees a lot of patients with diabetes that's out of control. In fact, he says, sometimes their blood sugar is "so high that you can't even record the number on their glucometer." Greene, a professor of medicine and history of medicine at Johns Hopkins University, started asking patients at his clinic in Baltimore why they had so much trouble keeping their blood sugar stable. He was shocked by their answer: the high cost of insulin. Greene decided to call some local pharmacies, to ask about low-cost options. He was told no such options existed. "Only then did I realize there is no such thing as generic insulin in the United States in the year 2015," he says. Greene wondered why that was the case. Why was a medicine more than 90 years old so expensive? He started looking into the history of insulin, and has published a paper about his findings in this week's issue of the New England Journal of Medicine. The story of insulin, it turns out, starts back in the late 1800s. That's when scientists discovered a link between diabetes and damaged cells in the pancreas — cells that produce insulin. In the early 1920s, researchers in Toronto extracted insulin from cattle pancreases and gave it to people who had diabetes, as part of a clinical trial. The first patient was a 14-year-old boy, who made a dramatic recovery. Most others recovered as well. Soon, insulin from pigs and cattle was being produced and sold on a massive scale around the world. But for some, the early forms of the medicine weren't ideal. Many people required multiple injections every day, and some developed minor allergic reactions. Over the next few decades, scientists figured out how to produce higher-quality insulin, Greene says. They made the drug purer, so recipients had fewer bad reaction Continue reading >>
In 1978, Genentech scientist Dennis Kleid toured a factory in Indiana where insulin was being made from pigs and cattle. “There was a line of train cars filled with frozen pancreases,” he says. At the time, it took 8,000 pounds of pancreas glands from 23,500 animals to make one pound of insulin. Diabetics lack this hormone, which regulates the amount of glucose in the blood. The manufacturer, Eli Lilly, needed 56 million animals per year to meet the increasing U.S. demand for the drug. They had to find a new insulin alternative, fast. Genentech had the expertise to make synthetic human insulin—in laboratories, from bacteria, using their recently-proven recombinant DNA technology. But could they make enough of the miniscule insulin molecules to replace these trainloads of pancreases and provide an alternative option for people living with diabetes? The scientists would have to coax the bacteria to produce insulin from the synthetic DNA at high enough concentrations to make an economically viable product. This meant that each bacteria needed to churn out so much of the protein per cell that if they could do it, they’d look like stuffed olives under a microscope. If not, Genentech’s work would have ended as a scientific curiosity, with no new option for diabetics. I don’t want to hear that word, impossible...tell me what you need to get it done. Kleid didn’t think they could get that kind of yield. He told Genentech founder, Bob Swanson, flat-out that it couldn’t be done. But Swanson refused to accept it. “I don’t want to hear that word, impossible,” he told Kleid. “Tell me what you need to get it done.” The high-stakes, high-pressure race to create synthetic insulin had started over a year earlier. Eli Lilly, the main U.S. producer of insulin, ha Continue reading >>
Human Insulin As Good As Costly Synthetic Versions
Human Insulin as Good as Costly Synthetic Versions FRIDAY, June 29, 2018 (HealthDay News) -- Human insulin is as safe and effective as newer, more expensive insulin analog drugs for people with type 2 diabetes , researchers report. The new study included people with type 2 diabetes who were followed for an average of 1.7 years after they started using insulin. "We found that for patients with type 2 diabetes in usual practice, the use of the more expensive insulin analogs did not appear to result in better safety -- at least as defined by hospital or emergency visits for hypoglycemia -- or better blood sugar control," said lead author Dr. Kasia Lipska. She is an assistant professor of medicine at Yale School of Medicine. "This suggests that many people with type 2 diabetes should consider starting with [human] insulin, instead of insulin analogs, especially if cost is an issue for them," she added in a Yale news release. About 25 percent of people with type 2 diabetes eventually require insulin to control their blood sugar. According to study co-author Andrew Karter, "For decades, people initiating insulin treatment were prescribed human insulin. Then in the 2000s, a new generation of long-acting insulin analogs emerged that were designed to mimic human insulin." Karter is a senior research scientist in Kaiser Permanente's division of research. Lipska explained that "the problem is that insulin analogs are much more expensive" than human insulin. A vial of insulin analog costs about $200 to $300, compared with $25 for a vial of human insulin. In the United States, the cost of analog insulin tripled between 2002 and 2013, the study authors noted. Previous research by Karter showed that higher out-of-pocket costs make diabetes patients less likely to take prescribed medi 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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How Did They Make Insulin From Recombinant Dna?
Recombinant DNA is a technology scientists developed that made it possible to insert a human gene into the genetic material of a common bacterium. This “recombinant” micro-organism could now produce the protein encoded by the human gene. Continue reading >>
Synthetic human insulin is identical to your own. However, relative to the rapid-acting insulin analogs, regular human insulin has several undesirable features. Synthetic human insulin is identical in structure to your own natural insulin. But when it is injected under the skin it doesn’t work as well as natural insulin. This is because injected human insulin clumps together and takes a long time to get absorbed. The activity of this synthetic human insulin is not well synchronized with your body’s needs. In this section, you will find information about: Fast-acting injected insulin Relative to the rapid-acting insulin analogs, Regular human insulin has undesirable features, such as a delayed onset of action, and variable peak and duration of action when it is injected under the skin. Because of this, fewer and fewer medical providers are prescribing Regular insulin. The delayed onset of action is the reason you have to inject the insulin and wait before eating. And the variable duration of action predisposes to low blood sugars long after the meal is over. REGULAR INSULIN IS LESS PREDICTABLE THAN RAPID-ACTING ANALOG VERSIONS when injected under the skin. NPH (Neutral Protamine Hagedorn) is an intermediate-acting human insulin that is used to cover blood sugar between meals, and to satisfy your overnight insulin requirement. A fish protein, protamine, has been added to the Regular human insulin to delay its absorption. This long acting insulin is a cloudy suspension that needs to be remixed thoroughly before each injection. Because NPH is a suspension of different sized crystals, it has a very unpredictable absorption rate and action. This results in more frequent low and high blood sugars. The use of NPH has declined with the availability of other long-acting insul Continue reading >>
This article is about the insulin protein. For uses of insulin in treating diabetes, see insulin (medication). Not to be confused with Inulin. Insulin (from Latin insula, island) is a peptide hormone produced by beta cells of the pancreatic islets, and it is considered to be the main anabolic hormone of the body. It regulates the metabolism of carbohydrates, fats and protein by promoting the absorption of, especially, glucose from the blood into fat, liver and skeletal muscle cells. In these tissues the absorbed glucose is converted into either glycogen via glycogenesis or fats (triglycerides) via lipogenesis, or, in the case of the liver, into both. Glucose production and secretion by the liver is strongly inhibited by high concentrations of insulin in the blood. Circulating insulin also affects the synthesis of proteins in a wide variety of tissues. It is therefore an anabolic hormone, promoting the conversion of small molecules in the blood into large molecules inside the cells. Low insulin levels in the blood have the opposite effect by promoting widespread catabolism, especially of reserve body fat. Beta cells are sensitive to glucose concentrations, also known as blood sugar levels. When the glucose level is high, the beta cells secrete insulin into the blood; when glucose levels are low, secretion of insulin is inhibited. Their neighboring alpha cells, by taking their cues from the beta cells, secrete glucagon into the blood in the opposite manner: increased secretion when blood glucose is low, and decreased secretion when glucose concentrations are high. Glucagon, through stimulating the liver to release glucose by glycogenolysis and gluconeogenesis, has the opposite effect of insulin. The secretion of insulin and glucagon into the Continue reading >>
How Is Artificial Insulin Made?
What a great question! Im not sure how much detail youre interested in, but here is the short answer. Insulin is created in a special non-disease-producing laboratory strain of E. coli bacteria (not the same type that causes diarrhea and kidney problems that you may be familiar with) that has been genetically altered by the addition of the gene for human insulin production. The bacteria produces the insulin which is then chemically harvested from the medium in which the bacteria is grown, purified and prepared for human use. Here is the long answer if you are interested: [Note: the following is adapted from Overview of Biotechnology at the End of the 20th Century. Please see that reference for even more details.] Modern biotechnology began when recombinant human insulin was first marketed in the United States in 1982. The effort leading up to this landmark event began in the early 1970s when research scientists developed protocols to construct vectors, by cutting out and pasting pieces of DNA together to create a new piece of DNA (recombinant DNA), that could be inserted into the bacterium, Escherichia coli (transformation). If one of the pieces of the new DNA included a gene which produced a protein enzyme that broke down a particular antibiotic, the bacterium would be resistant to that antibiotic and could grow in a medium containing it. To the piece of DNA that conferred resistance of Escherichia coli to a particular antibiotic was added the human gene for the making of insulin. If this recombinant DNA containing the human insulin gene was used to transform Escherichia coli,and the bacteria were plated on an agar plate containing the antibiotic, the bacteria that grew contained not only the antibiotic resistant gene but also the insulin gene. Additional new pieces o Continue reading >>