This article was distributed via email by the Juvenile Diabetes Research Foundation on Feb. 10, 2005. We repost it here for educational purposes only.
The Diabetes Center at UCSF and the UCSF Pediatric Diabetes Program are launching a study to assess the ability of an over-the-counter antioxidant to prevent or delay the long-term complications of type 1 diabetes.
Most people are aware that the long-term effects of diabetes include blindness, kidney failure, and nerve damage. Recently, researchers have discovered that high blood sugar increases the amount of free-radicals in those with diabetes. It is believed that these free-radicals cause retinopathy (eye damage), nephropathy (kidney damage) and neuropathy (nerve damage) by a process called “oxidative stress”.
Researchers at UCSF believe that alpha-lipoic acid, a potent anti-oxidant, could decrease oxidative stress, thereby preventing or delaying the devastating long-term complications of diabetes.
Although alpha-lipoic acid is gaining recognition as an effective treatment for diabetes complications after they have occurred, its ability to prevent or delay these complications has not yet been studied in humans. The UCSF study will be the first to assess if this natural anti-oxidant has a future role in preventing or delaying the long-term complications of type 1 diabetes.
In this study, 30 adolescents with type 1 diabetes will be given alpha-lipoic acid, and 10 adolescents with type 1 diabetes will be given placebo pills. The amount of oxidative stress before and after 3 months of treatment will be compared. If the results are promising, a more extensive study will be launched to further explore if alpha-lipoic acid can successfully prevent or delay eye, kidney, and nerve damage.
The study's principal investigators include: Dr. Stephen Gitelman, Professor of Clinical Pediatrics and Director of the UCSF Pediatric Diabetes Program, and Dr. Eric Huang, Clinical Fellow in the Division of Pediatric Endocrinology.
If you or your child is interested in participating in this study, please contact Dr. Huang by phone – (415)-476-8216, or e-mail huange1@itsa.ucsf.edu
To learn more about diabetes research at UCSF, visit http://m1e.net/c?22835818-iHLZru3hKBFHA%40846840-OD4y7WPERUQ9Y
Sunday, February 20, 2005
Diabetes Center at UCSF researchers in national beta cell effort
This article was distributed by the Diabetes Center at UCSF on Feb. 15, 2005. We repost it here for educational purposes only.
Diabetes Center researchers in national beta cell effort
In keeping with the Diabetes Center’s tradition of collaboration, faculty members Michael German, MD, Matthias Hebrok, PhD, and Didier Stainier, PhD are working in a national consortium with nearly twenty other renowned U.S. scientists to "fast track" the creation of insulin-producing beta cells.
This esteemed group of researchers, known as the Beta Cell Biology Consortium (BCBC), was formed by the National Institutes of Health (NIH) in 2001 to advance the scientific community's understanding of pancreatic islet development and function. It is believed that this knowledge is critical if we are to succeed in converting human stem cells into insulin-producing beta cells.
In addition to sitting on the Consortium’s steering committee, Dr. German heads up the “Molecular Control of Pancreatic Islet Development” program of the BCBC. The program utilizes zebrafish, and human stem cells as model systems. In mouse model systems, the consortium is examining new strategies to rapidly manipulate genes that play essential roles in the development of the pancreas, with the aim to determine exactly what genes play a role in beta cell development and if this knowledge can be used to create new sources of beta cells. Dr. Hebrok’s BCBC project aims to define the role of neuronal guiding molecules during islet formation.
In addition to the Beta Cell Biology Consortium, Diabetes Center researchers are actively involved in a number of other important national and international collaborations, such as Type 1 Diabetes TrialNet and the Type 1 Diabetes Genetics Consortium, as well as being home to the Immune Tolerance Network.
Diabetes Center researchers in national beta cell effort
In keeping with the Diabetes Center’s tradition of collaboration, faculty members Michael German, MD, Matthias Hebrok, PhD, and Didier Stainier, PhD are working in a national consortium with nearly twenty other renowned U.S. scientists to "fast track" the creation of insulin-producing beta cells.
This esteemed group of researchers, known as the Beta Cell Biology Consortium (BCBC), was formed by the National Institutes of Health (NIH) in 2001 to advance the scientific community's understanding of pancreatic islet development and function. It is believed that this knowledge is critical if we are to succeed in converting human stem cells into insulin-producing beta cells.
In addition to sitting on the Consortium’s steering committee, Dr. German heads up the “Molecular Control of Pancreatic Islet Development” program of the BCBC. The program utilizes zebrafish, and human stem cells as model systems. In mouse model systems, the consortium is examining new strategies to rapidly manipulate genes that play essential roles in the development of the pancreas, with the aim to determine exactly what genes play a role in beta cell development and if this knowledge can be used to create new sources of beta cells. Dr. Hebrok’s BCBC project aims to define the role of neuronal guiding molecules during islet formation.
In addition to the Beta Cell Biology Consortium, Diabetes Center researchers are actively involved in a number of other important national and international collaborations, such as Type 1 Diabetes TrialNet and the Type 1 Diabetes Genetics Consortium, as well as being home to the Immune Tolerance Network.
New research into gene-disease relationship
This we distributed Feb. 15 by the Diabetes Center at UCSF. We repost this very technical but interesting article here for educational purposes only.
Don't shoot the messenger... silence it!
Michael McManus, PhD is exploring new ways to stop bad genes
A new tool that gives researchers the ability to block disease-causing genes is the next wave in biotechnology. If successful, “RNA interference” (known as RNAi) could provide new cures for everything from cancer to HIV to diabetes. Dr. Michael McManus, a world leader in RNAi, recently moved his MIT laboratory to the Diabetes Center at UCSF to focus his groundbreaking research on the problem of diabetes.
--
In the era of the human genome, it is clear that our genes play a vital role in determining our health. Mutations in specific genes, either inherited or caused by environmental damage, are responsible for a wide array of human disease. Subverting these mutated genes and the damage they cause would address disease at its source, providing long-lasting or permanent cures.
But exactly how do you stop a bad gene? There are several ways. For one, you could target the DNA that encodes the bad gene. Known as gene therapy, this technique has met with only limited success. On the other hand, you could target the proteins that precipitate the ill-effects of the bad genes. While this has proven more practical, in many cases, one bad gene can affect the function of many different proteins and so therapies targeted at proteins are often only partially effective.
RNA, the lesser-known cousin of DNA offers a third technique. RNA is an intermediary in the creation of proteins from genes. Single-stranded RNA molecules, known as messenger RNA act as templates for constructing new proteins encoded by the gene. Therefore, shutting down the RNA of a specific gene should do the trick. To date, attempts at targeting RNA with “antisense” pieces of artificial single-stranded RNA that bind and disable the messenger RNA have not been overly successful.
However, in 1998 a new form of RNA was discovered known as “small interfering RNA” or siRNA. These short, single stranded molecules are part of an ancient mechanism for regulating genes that is found in both plants and in animals as diverse as yeast and humans. Each piece of siRNA is specific for a given gene and is capable of stopping its expression, halting the effects of the mutation or overexpression that is causing a disease.
According to Dr. McManus, “siRNA acts like a one-way volume dial on a radio -- quickly turning down the amount of a specific gene that is expressed. We call the process ‘gene silencing’."
Over 300 hundred of these small RNA volume knobs have been discovered. Now called microRNAs, scientists are only beginning to determine which specific genes that each acts upon. According to McManus, however, one microRNA known as miR-375 was recently found to regulate insulin secretion.
“We certainly expect that we will uncover additional control RNAs that relate to both type 1 and type 2 diabetes,” says McManus. “In the meantime, we are working to learn more about how siRNA functions and how we can harness this discovery to develop new therapies.”
Dr. McManus is currently investigating a gene called “Dicer,” which was originally discovered through the Human Genome Project. Dicer is a naturally occurring protein that acts like a pair of scissors to cut double stranded RNA into the siRNAs that regulate gene expression. Without it, gene silencing doesn’t work. So determining exactly how Dicer functions and the pathways that microRNAs use to silence specific genes may lead to new treatments for diseases where gene silencing has broken down. His studies may also offer ways to enhance the "tailored siRNAs" that could be used to treat diseases like diabetes.
Researchers have already tailor-made siRNA that target the gene Phosphatase-1B (PTP-1B), which is involved in insulin resistance.
While this treatment gives the appearance of a "magic bullet", McManus says the biggest challenge so far is finding ways to deliver siRNAs to the cells.
“In organisms such as plants and worms, siRNAs are easily taken up by cells. In mammals, siRNAs need help from chemical carriers,” he says. Many pharmaceutical companies are working day and night to develop chemical treatments intended to deliver the siRNA to the intended target. "RNAi has transformed the way scientists are performing gene function studies and has consumed the biotech industry like wildfire. It was recently given the title of 'Breakthrough of the Year' by Science magazine, and Fortune magazine has heralded it as 'Biotech's Billion-Dollar Breakthrough'." McManus says, "I believe it will revolutionize the way we look at medicine".
“In addition to his work with Dicer, McManus is collaborating with other Diabetes Center scientists like Mike German and Matthias Hebrok. Among other things, they are looking to determine the role of microRNAs in beta cell development.
“There is much research to be done” he says. “I came here because of the fantastic forward-thinking attitude in research and medicine. Look around you, UCSF is a place of tremendous growth and accomplishments. The UCSF Diabetes Center is at the forefront -- it is a place where my research can contribute to the major advances being made in both basic science and the curing of diseases such as diabetes.”
Don't shoot the messenger... silence it!
Michael McManus, PhD is exploring new ways to stop bad genes
A new tool that gives researchers the ability to block disease-causing genes is the next wave in biotechnology. If successful, “RNA interference” (known as RNAi) could provide new cures for everything from cancer to HIV to diabetes. Dr. Michael McManus, a world leader in RNAi, recently moved his MIT laboratory to the Diabetes Center at UCSF to focus his groundbreaking research on the problem of diabetes.
--
In the era of the human genome, it is clear that our genes play a vital role in determining our health. Mutations in specific genes, either inherited or caused by environmental damage, are responsible for a wide array of human disease. Subverting these mutated genes and the damage they cause would address disease at its source, providing long-lasting or permanent cures.
But exactly how do you stop a bad gene? There are several ways. For one, you could target the DNA that encodes the bad gene. Known as gene therapy, this technique has met with only limited success. On the other hand, you could target the proteins that precipitate the ill-effects of the bad genes. While this has proven more practical, in many cases, one bad gene can affect the function of many different proteins and so therapies targeted at proteins are often only partially effective.
RNA, the lesser-known cousin of DNA offers a third technique. RNA is an intermediary in the creation of proteins from genes. Single-stranded RNA molecules, known as messenger RNA act as templates for constructing new proteins encoded by the gene. Therefore, shutting down the RNA of a specific gene should do the trick. To date, attempts at targeting RNA with “antisense” pieces of artificial single-stranded RNA that bind and disable the messenger RNA have not been overly successful.
However, in 1998 a new form of RNA was discovered known as “small interfering RNA” or siRNA. These short, single stranded molecules are part of an ancient mechanism for regulating genes that is found in both plants and in animals as diverse as yeast and humans. Each piece of siRNA is specific for a given gene and is capable of stopping its expression, halting the effects of the mutation or overexpression that is causing a disease.
According to Dr. McManus, “siRNA acts like a one-way volume dial on a radio -- quickly turning down the amount of a specific gene that is expressed. We call the process ‘gene silencing’."
Over 300 hundred of these small RNA volume knobs have been discovered. Now called microRNAs, scientists are only beginning to determine which specific genes that each acts upon. According to McManus, however, one microRNA known as miR-375 was recently found to regulate insulin secretion.
“We certainly expect that we will uncover additional control RNAs that relate to both type 1 and type 2 diabetes,” says McManus. “In the meantime, we are working to learn more about how siRNA functions and how we can harness this discovery to develop new therapies.”
Dr. McManus is currently investigating a gene called “Dicer,” which was originally discovered through the Human Genome Project. Dicer is a naturally occurring protein that acts like a pair of scissors to cut double stranded RNA into the siRNAs that regulate gene expression. Without it, gene silencing doesn’t work. So determining exactly how Dicer functions and the pathways that microRNAs use to silence specific genes may lead to new treatments for diseases where gene silencing has broken down. His studies may also offer ways to enhance the "tailored siRNAs" that could be used to treat diseases like diabetes.
Researchers have already tailor-made siRNA that target the gene Phosphatase-1B (PTP-1B), which is involved in insulin resistance.
While this treatment gives the appearance of a "magic bullet", McManus says the biggest challenge so far is finding ways to deliver siRNAs to the cells.
“In organisms such as plants and worms, siRNAs are easily taken up by cells. In mammals, siRNAs need help from chemical carriers,” he says. Many pharmaceutical companies are working day and night to develop chemical treatments intended to deliver the siRNA to the intended target. "RNAi has transformed the way scientists are performing gene function studies and has consumed the biotech industry like wildfire. It was recently given the title of 'Breakthrough of the Year' by Science magazine, and Fortune magazine has heralded it as 'Biotech's Billion-Dollar Breakthrough'." McManus says, "I believe it will revolutionize the way we look at medicine".
“In addition to his work with Dicer, McManus is collaborating with other Diabetes Center scientists like Mike German and Matthias Hebrok. Among other things, they are looking to determine the role of microRNAs in beta cell development.
“There is much research to be done” he says. “I came here because of the fantastic forward-thinking attitude in research and medicine. Look around you, UCSF is a place of tremendous growth and accomplishments. The UCSF Diabetes Center is at the forefront -- it is a place where my research can contribute to the major advances being made in both basic science and the curing of diseases such as diabetes.”
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