Gene Could Help Explain Insulin Resistance
Health researchers have known for decades that Type 2 diabetes results from a phenomenon called insulin resistance, but what causes insulin resistance has remained a mystery. Now, researchers at the Stanford University School of Medicine and the University of Wisconsin-Madison have begun to untangle a web of connections that includes a gene; mitochondria, which produce energy for cells; insulin resistance; and how well the body’s metabolism functions. “We’ve identified a mechanism for insulin resistance that involves a gene that ties insulin resistance to mitochondrial function,” said Joshua Knowles, MD, PhD, an assistant professor of cardiovascular medicine at Stanford. A paper describing the work was published in the Oct. 4 issue of Cell Reports. Knowles is the senior author, and Indumathi Chennamsetty, PhD, a postdoctoral scholar at Stanford, is the lead author. Insulin is a hormone secreted by the pancreas that helps fat and muscle cells take glucose from the blood. When a person’s cells stop responding to insulin, the person has insulin resistance and glucose builds up in the blood, signaling the pancreas to produce ever more insulin. Insulin resistance severe enough to damage body tissues is common. One 2015 study estimated that nearly 35 percent of all U.S. adults are sufficiently insulin-resistant to be at greater risk of diabetes and cardiovascular disease. The environmental causes of the skyrocketing rate of insulin resistance in the United States include poor diet and sedentary habits, but the molecular mechanisms have been unknown, said Knowles. Suspect gene Previous work by Knowles and his team linked a variant of a human gene called NAT2 with insulin resistance in humans. In mice, suppressing a similar gene, called Nat1, caused metabolic dysfunct Continue reading >>
Genetic Variant Is Linked To Obesity And Insulin Resistance
Follow all of ScienceDaily's latest research news and top science headlines ! Genetic variant is linked to obesity and insulin resistance A large study in people at risk of diabetes has found a direct association between the presence of a small genetic alteration in a hormone receptor and increased body fat and insulin resistance. The results suggest an adverse role for a previously described genetic variant, the BclI polymorphism. A large study in people at risk of diabetes has found a direct association between the presence of a small genetic alteration in a hormone receptor and increased body fat and insulin resistance. The results, presented June 26 at The Endocrine Society's 94th Annual Meeting in Houston, suggest an adverse role for a previously described genetic variant, the BclI polymorphism. "Our findings support the idea that even small variations in hormone receptor sensitivity can have metabolic implications, such as obesity or diabetes," said co-author Bastiaan Havekes, MD, PhD, of Maastricht University Medical Center, Maastricht, the Netherlands. "Endocrinologists should not just focus on hormone levels themselves. Taking into account hormone receptor sensitivity could help in better understanding hormone-mediated effects on metabolism," he said. The inherited BclI polymorphism occurs in the gene encoding for the glucocorticoid receptor, which controls the actions of glucocorticoids, steroid hormones that affect every system in the body. This small variant makes the receptor more sensitive to glucocorticoids, resulting in greater effects with similar hormone levels, Havekes said. The effects of this change appear to be similar to, although much smaller than, the excessive glucocorticoid exposure that can occur from certain medications or diseases, Havekes Continue reading >>
Insulin Gene Expression Is Regulated By Dna Methylation
Insulin Gene Expression Is Regulated by DNA Methylation Current address: Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita-City, Japan Affiliation Department of Diabetes, Endocrinology, & Metabolism, Research Institute of City of Hope, Duarte, California, United States of America Current address: Department of Orthopedic Surgery, Rush University Medical Center, Chicago, Illinois, United States of America Affiliation Department of Biology, Beckman Research Institute of City of Hope, Duarte, California, United States of America Affiliation Department of Diabetes, Endocrinology, & Metabolism, Research Institute of City of Hope, Duarte, California, United States of America Affiliation Department of Diabetes, Endocrinology, & Metabolism, Research Institute of City of Hope, Duarte, California, United States of America Affiliation Department of Diabetes, Endocrinology, & Metabolism, Research Institute of City of Hope, Duarte, California, United States of America Affiliation Department of Diabetes, Endocrinology, & Metabolism, Research Institute of City of Hope, Duarte, California, United States of America Affiliation Department of Diabetes, Endocrinology, & Metabolism, Research Institute of City of Hope, Duarte, California, United States of America Affiliation Department of Biology, Beckman Research Institute of City of Hope, Duarte, California, United States of America Affiliation Department of Diabetes, Endocrinology, & Metabolism, Research Institute of City of Hope, Duarte, California, United States of America Continue reading >>
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Genetic engineering The control of all the normal activities of a bacterium depends upon its single chromosome and small rings of genes called plasmids. In genetic engineering pieces of chromosome from a different organism can be inserted into a plasmid. This allows the bacteria to make a new substance. the gene the genetic engineers want may be in a human chromosome - it might be the gene for insulin production they use an enzyme to cut the insulin gene out of the chromosome plasmids are then removed from bacterial cells the plasmids are cut open with an enzyme a human insulin gene is inserted into each plasmid the genetic engineers encourage the bacteria to accept the genetically modified plasmids bacteria with the insulin gene are then multiplied each bacterium will produce a tiny volume of insulin by culturing the genetically engineered bacteria, limitless supplies of insulin may be produced Genetic engineering is used for the production of substances which used to be both expensive and difficult to produce. Examples include: insulin for the control of diabetes antibiotics such as penicillin various vaccines for the control of disease Genetic engineering and insulin production Genetic engineering is a way of producing organisms which have genotypes best suited for a particular function. In the past man has used selective breeding to achieve this. This was done by choosing only his most suitable animals and plants for breeding. Genetic engineering has several advantages over selective breeding. Some are: particular single characteristics can be selected the selection may be quicker a desirable characteristic can be transferred from one species to another There are dangers involved with genetic engineering since it involves creating completely new strains of bacteria. Continue reading >>
Type 1 Diabetes Associates With The Insulin Gene.
Background The insulin gene (INS) on chromosome 11p 15 codes for the islet beta cell protein, pre-proinsulin, a peptide of 110 amino acids. Preproinsulin, a precursor, is processed by proteases to proinsulin by removal of the signal peptide and ultimately to biologically active insulin after the cleavage of C-peptide (figure 1). Autoimmunity to insulin in diabetes In type 1 diabetes insulin producing beta cells are the focus of autoimmune destruction, and their loss results in diabetes. Evidence from the NOD mouse model of autoimmune diabetes suggests that insulin is the primary autoantigen in this model   and autoantibodies to insulin can indeed be detected in humans in the first year of life. Further evidence that insulin itself plays a fundamental role in the pathogenesis of autoimmune diabetes emerged when genetic associations between INS and type 1 diabetes were reported by Bell and colleagues in 1984 in a relatively small study of 113 affected individuals compared with 83 healthy controls and 76 with type 2 diabetes. This association has been consistently replicated in every genetic analysis since: genome wide association studies (GWAS) have confirmed that the insulin gene locus is the second most important susceptibility locus after the HLA locus, contributing about 10% of genetic susceptibility. Molecular Biology of the insulin Gene The insulin gene comprises 3 exons and 2 introns interspersed with several polymorphisms in linkage disequilibrium. Type 1 diabetes is most closely associated with a variable number tandem repeat (VNTR) in the INS promoter  about 0.5Kb upstream of the transcription start site. Although highly polymorphic, three different classes of alleles exist at this locus, short class 1 variants (26-63 repeats), intermediate cla Continue reading >>
Mutations In The Insulin Gene Can Cause Neonatal Diabetes
Mutations in the insulin gene can cause neonatal diabetes Mutations in the insulin gene can cause permanent neonatal diabetes, an unusual form of diabetes that affects very young children and results in lifelong dependence on insulin injections, report researchers from the University of Chicago and Peninsula University (Exeter, UK) in Sept. 18, 2007, issue of the Proceedings of the National Academy of Sciences, published early online. Although abnormal insulin has been associated with milder cases of type 2 diabetes since the discovery of insulin Chicago in 1979, this is the first time that an insulin mutation has been connected to severe diabetes with onset early in life. The researchers describe 10 mutations, found in 21 patients from 16 families. They suspect that the mutations alter the way insulin folds during its synthesis. They suggest that these improperly folded proteins interfere with other cellular processes in ways that eventually kill the cells that produce insulin. This is a novel and potentially treatable cause of diabetes in infants, said study author Louis Philipson , MD, PhD, professor of medicine at the University of Chicago. Its exciting because each of these patients has one normal insulin gene as well as one mutated gene. If we could detect the disease early enough and somehow silence the abnormal gene, or just protect insulin-producing cells from the damage caused by misfolding, we might be able to preserve or restore the patients own insulin production. The effort to learn more about possible genetic causes of neonatal diabetes followed a flurry of publicity last September. Philipson and colleagues at the University of Chicago using a protocol developed by co-author Andrew Hattersley, MD, Professor of Molecular Medicine at Peninsula University w Continue reading >>
Gene Therapy For Type 1 Diabetes Aims To Eliminate Daily Insulin Injections
Researchers at the University of Wisconsin School of Medicine and Public Health are one step closer to developing a gene therapy for Type 1 diabetes mellitus – a development that could one day eliminate the need for daily insulin shots and provide a way to better regulate glucose metabolism, a factor critical for preventing the most problematic complications of the disease. The study, reported in the June 27, 2013, issue of the journal PLOS ONE, describes a small sequence of DNA that, when injected into the veins of diabetic rats, create insulin-producing cells that help normalize blood sugar levels and perfect the regulation of glucose metabolism. It is the first known study to demonstrate how a DNA-based insulin gene therapy has the potential to treat type 1 diabetes. “Even we were surprised that a single injection could provide perfect glycemic control for up to six weeks,” says Hans Sollinger, the Folkert O. Belzer Professor of Surgery at the UW School of Medicine and Public Health. “After receiving the therapy, the diabetic rats had insulin and glucose levels that resembled exactly what you would find in healthy animals.” The DNA sequence of the therapy works by sensing an increase in glucose concentrations in the body (such as after a meal) and then, with the help of a glucose inducible response element (GIRE), prompts the injected DNA to produce insulin, similar to the way normal pancreatic cells do. But instead of targeting pancreatic cells, the therapy exclusively targets the liver. “We chose the liver as the ideal target for this therapy because of its ability to regenerate,” says Sollinger. “In order for the therapy to be effective, the DNA needs to enter and attach to millions of cells, so the liver’s ability to replace dead cells was an ob Continue reading >>
- Betalin Aims To End Insulin Injections By Treating Type 1 Diabetes With Cell Transplants
- New diabetes treatment could eliminate need for insulin injections
- Relative effectiveness of insulin pump treatment over multiple daily injections and structured education during flexible intensive insulin treatment for type 1 diabetes: cluster randomised trial (REPOSE)
For bacteria to make insulin, where do they get the insulin gene to insert into the bacteria? Back in the 1970's scientists managed to coax bacteria into making the insulin that many people need to treat their diabetes. They did this by putting the human insulin gene into the bacteria. The insulin gene they used came from human DNA. The scientists were able to get this gene in a couple of different ways. Neither of which was very easy back in the 70's! One group managed to make it on a machine called a DNA synthesizer. Like its name sounds, this machine makes DNA. Luckily the insulin gene is small since these machines could only make small snippets of DNA. A second group managed to fish it out of human DNA. This was done by putting random pieces of human DNA into bacteria and finding the bacterium that had the insulin gene. This is really hard to do but used to be the only way to get big pieces of DNA. Nowadays, what with the human genome project, it'd be much easier. By knowing just a bit about the gene they're interested in, scientists can just go look it up on the computer. Then they can simply pluck the DNA they're interested in right out of a tube of human DNA. Of course getting the gene isn't enough. You also need to get it into bacteria and have the bacteria be able to read the gene. Then you need to purify the insulin away from the bacteria. Luckily you only asked about the first part so I'll focus on that. What I thought I'd do is go over how scientists originally got the insulin gene. Then we'll look at what they might do now in a similar situation. But first, we're going to need to go into a little background. We need to go over what genes and proteins are and how they're related. Only then will we see how scientists were able to go from the insulin protein Continue reading >>
What Is Genetic Engineering?
Genetic engineering refers to the direct manipulation of DNA to alter an organism’s characteristics (phenotype) in a particular way. What is genetic engineering? Genetic engineering, sometimes called genetic modification, is the process of altering the DNA? in an organism’s genome?. This may mean changing one base pair? (A-T or C-G), deleting a whole region of DNA, or introducing an additional copy of a gene?. It may also mean extracting DNA from another organism’s genome and combining it with the DNA of that individual. Genetic engineering is used by scientists to enhance or modify the characteristics of an individual organism. For example, genetic engineering can be used to produce plants that have a higher nutritional value or can tolerate exposure to herbicides. How does genetic engineering work? To help explain the process of genetic engineering we have taken the example of insulin, a protein? that helps regulate the sugar levels in our blood. Normally insulin? is produced in the pancreas?, but in people with type 1 diabetes? there is a problem with insulin production. People with diabetes therefore have to inject insulin to control their blood sugar levels. Genetic engineering has been used to produce a type of insulin, very similar to our own, from yeast and bacteria? like E. coli?. This genetically modified insulin, ‘Humulin’ was licensed for human use in 1982. The genetic engineering process A small section is then cut out of the circular plasmid by restriction enzymes, ‘molecular scissors’. The gene for human insulin is inserted into the gap in the plasmid. This plasmid is now genetically modified. The genetically modified plasmid is introduced into a new bacteria or yeast cell. This cell then divides rapidly and starts making insulin. To create Continue reading >>
Scientists Report Using Bacteria To Produce The Gene For Insulin
Archives |Scientists Report Using Bacteria To Produce the Gene for Insulin Scientists Report Using Bacteria To Produce the Gene for Insulin May 24, 1977, Page 1 The New York Times Archives WASHINGTON, May 23—Scientists in California reported today that bacteria bred in laboratories have been engineered to make the gene for insulin, a developmeat that could provide a virtually limitless supply of the vital hormone and have an important impact on the treatment and understanding of diabetes. Giving bacteria the ability to make insulin has been one of the most discussed goals of recombinant. DNA research, controversial realm of genetic experimentation known popularly as gene splicing. What the scientists at the University of California at San Francisco did was to transplant into bacteria the genes from rat cells that carry the genetic instructions for making insulin. It is believed to he the first time this was accomplished with the gene for making insulin, or any other important animal hormone. Now, the scientists said there should be no major. scientific obstacles to doing the same with the genes for human insulin. But the worldwide demand for insulin is believed to be putting some strain on these supplies. And some diabetics develop allergic reactions to the animal insulin or its chemical precursors. It is conservatively estimated that there are more than two million diabetics in this country. A copious supply of purified human insulin would therefore he an important resource. Drug companies are known to he interested in the possibilities of producing insulin in bacterial cultures, I The experiments reported today are helieved to be an important step toward production of that kind. In order to live, mammals and humans need insulin, a protein hormone secreted Laborator Continue reading >>
Ins Insulin [ Homo Sapiens (human) ]
Data suggest early peaks in glucagon-like peptide-1 and glucagon secretion/blood level together trigger exaggerated insulinotropic response (high insulin secretion/level) to eating and consequent hypoglycaemia in patients with postprandial hypoglycaemia as a postoperative complication following Roux-en-Y gastric bypass for obesity complicated by type 2 diabetes; this retrospective cohort study was conducted in London. Studies on the susceptibility to aggregation of truncated analogs of insulin amyloidogenic core show three groups of peptides. Truncation of A13-A419 fragment shows that fibrous structures are formed by all peptides bearing (13)H-LeuTyr-OH(14). Propensity to aggregation was found for (16)H-TyrLeu-OH(17) B12-B17 fragment. Insulin secretion by pancreatic beta-cells increases after adrenalectomy for aldosterone-producing adenomas; adrenalectomy in these patients prevents primary aldosteronism; such data suggest that aldosterone excess inhibits insulin secretion by pancreatic beta-cells. This retrospective study was conducted in Japan. Continue reading >>
The Insulin Gene Is Located On Chromosome 11 In Humans
The polypeptide hormone insulin is required for normal glucose homeostasis. Insulin deprivation results in diabetes, a disease affecting up to 5% of the human population1,2. In some animals there are two insulin genes3; however, in most others, including humans, a single gene is present. The conclusion that there is a single insulin gene in humans is based on the finding of a single insulin species and on genetic studies involving mutant insulin alleles4,5. As the pattern of inheritance of insulin defects is not sex linked, the insulin gene must be located on an autosomal chromosome5. Recently, genomic DNA segments containing the human and rat insulin genes have been cloned and the DNA has been sequenced6–8. The fact that mouse and rat insulins are identical3 suggests that the insulin gene sequences and organization are similar. A knowledge of the restriction endonuclease map for the human and mouse insulin genes enables human or mouse insulin DNA sequences to be distinguished in somatic cell hybrids between the two species. In the present study, somatic cell hybrid gene mapping methodologies9 have been used to determine the chromosome localization10 of the human insulin gene. Human–mouse cell hybrids with different numbers and combinations of human chromosomes were examined for the presence of specific human chromosomes and the human insulin gene using cloned human and rat cDNA probes. A 14-kilobase DNA fragment containing the human insulin gene was present in some cell hybrids and was easily distinguished from the DNA fragments containing the mouse insulin gene found in all cell hybrids. Co-existence of the 14-kilobase fragment and chromosome 11 indicate that the insulin gene resolves on chromosome 11 in humans. Continue reading >>
The polypeptide hormone insulin is required for normal glucose homeostasis. Lack of insulin or insulin insufficiency leads to diabetes that affects up to 5% of the human population. Gene location Insulin is formed as a precursor protein preproinsulin. This is coded by the INS gene. In some animals there are two insulin genes or two genes that code for insulin. In most animals, including humans, a single gene is present. The hypothesis of a single gene is enhanced by the genetic studies of inheritance of defects in the insulin gene. In addition, there seems to be no sex-predilection while inheriting defects in the insulin gene. This means that the gene coding for insulin does not lie in the sex chromosomes (XX for females and XY for males) but in the autosomes (the 20 pairs of chromosomes barring the one pair of sex chromosomes). The insulin gene has been recently uncoded in its complete form in genomic studies. Human and rat insulin genes have been cloned and the DNA has been sequenced. It was seen that mouse and rat insulins are identical and they have similar gene sequences and organization. Similarities in genetic sequences in human have been found as well. Studies reveal that the 14-kilobase fragment that codes for insulin lies on the chromosome 11 in humans. Gene stimulation and inhibition The insulin gene is expressed almost exclusively in pancreatic β-cells. Glucose in blood is the major stimulant that regulates the insulin gene expression and enables the beta cells to produce insulin and maintain an adequate store of intracellular insulin to sustain the secretory demand. Glucose in blood acts via transcription factors like pancreatic/duodenal homeobox-1 (PDX-1, mammalian homologue of avian MafA/L-Maf (MafA), Beta2/Neuro D (B2)), and controls the rate of transcr 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 >>
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 >>
- The Vaccine Against Diabetes Has Been Officially Announced And The Entire World Is Celebrating The News!
- Vaccine to Reverse Diabetes Has Been Officially Announced and the Whole World is Celebrating the News!
- The Vaccine Against Diabetes Has Been Officially Announced And The Entire World Is Celebrating The News!