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Discovery of new gene associated with diabetes risk suggests link with body clock
December 08, 2008A connection between the body clock and abnormalities in metabolism and diabetes has been suggested in new research by an international team involving the University of Oxford, the Wellcome Trust Sanger Institute and the MRC Epidemiology Unit in Cambridge.
The researchers have identified a gene involved in the way the body responds to the 24 hour day-night cycle that is strongly linked to high blood sugar levels and an increased risk of type 2 diabetes. The results of the genome-wide association scan are published in Nature Genetics.
"We have extremely strong, incontrovertible evidence that the gene encoding melatonin receptor 1B is associated with high fasting glucose levels and increased risk of type 2 diabetes," says Professor Mark McCarthy of the Oxford Centre for Diabetes, Endocrinology and Metabolism at the University of Oxford.
Melatonin is a hormone that is strongly tied to control of our sleep-wake cycles, with concentrations in the blood peaking at night-time and dipping during the day. As a result, melatonin is implicated in conditions like jetlag and sleep disorders.
Disrupted sleep patterns are known to be associated with a range of health problems including metabolic disorders like diabetes, but it is not understood how they are connected. In identifying a link between a melatonin receptor and blood sugar levels, this study provides genetic evidence that mechanisms controlled by our body clock are connected to the machinery that keeps us metabolically healthy. It seems likely that the action of melatonin on the pancreas is being disturbed in this case, the researchers suggest.
The international research collaboration combined ten genome-wide association scans involving a total of over 36,000 individuals of European descent. A variant in the gene encoding melatonin receptor 1B (MTNR1B) showed a rise of 0.07 mmol/l in fasting glucose level on average and a 9% increase in risk of type 2 diabetes for each copy of the gene variant inherited from a parent.
"High fasting glucose levels are early markers of diabetes and this observation provides important clues about the possible mechanisms linking genes to diabetes risk," says Professor Nick Wareham, Director of the MRC Epidemiology Unit in Cambridge.
Other genes have previously been shown to be associated with high blood sugar levels, but have not shown an increase in diabetes risk. The melatonin receptor found in this genome-wide study is the first gene to be linked to both high blood sugar and increased risk of diabetes.
"Although levels of glucose in the blood are used to diagnose diabetes, most of the genes previously associated with high glucose levels do not increase risk of diabetes," says Dr Inês Barroso from the Wellcome Trust Sanger Institute. "We have found a variant - a G in the genome in place of a C - in MTNR1B. This single-letter change influences both sugar levels and diabetes. This remarkable result should allow us to gain new insight into this problem."
Wellcome Trust Sanger Institute
Melatonin is a hormone that is strongly tied to control of our sleep-wake cycles, with concentrations in the blood peaking at night-time and dipping during the day. As a result, melatonin is implicated in conditions like jetlag and sleep disorders.
Disrupted sleep patterns are known to be associated with a range of health problems including metabolic disorders like diabetes, but it is not understood how they are connected. In identifying a link between a melatonin receptor and blood sugar levels, this study provides genetic evidence that mechanisms controlled by our body clock are connected to the machinery that keeps us metabolically healthy. It seems likely that the action of melatonin on the pancreas is being disturbed in this case, the researchers suggest.
The international research collaboration combined ten genome-wide association scans involving a total of over 36,000 individuals of European descent. A variant in the gene encoding melatonin receptor 1B (MTNR1B) showed a rise of 0.07 mmol/l in fasting glucose level on average and a 9% increase in risk of type 2 diabetes for each copy of the gene variant inherited from a parent.
"High fasting glucose levels are early markers of diabetes and this observation provides important clues about the possible mechanisms linking genes to diabetes risk," says Professor Nick Wareham, Director of the MRC Epidemiology Unit in Cambridge.
Other genes have previously been shown to be associated with high blood sugar levels, but have not shown an increase in diabetes risk. The melatonin receptor found in this genome-wide study is the first gene to be linked to both high blood sugar and increased risk of diabetes.
"Although levels of glucose in the blood are used to diagnose diabetes, most of the genes previously associated with high glucose levels do not increase risk of diabetes," says Dr Inês Barroso from the Wellcome Trust Sanger Institute. "We have found a variant - a G in the genome in place of a C - in MTNR1B. This single-letter change influences both sugar levels and diabetes. This remarkable result should allow us to gain new insight into this problem."
Wellcome Trust Sanger Institute
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An atomic-level look at an HIV accomplice
Since the discovery in 2007 that a component of human semen called SEVI boosts infectivity of the virus that causes AIDS, researchers have been trying to learn more about SEVI and how it works, in hopes of thwarting its infection-promoting activity.
Scripps research scientists find new link between insulin and core body temperature
A team led by scientists at The Scripps Research Institute have discovered a direct link between insulin-a hormone long associated with metabolism and metabolic disorders such as diabetes-and core body temperature.
Scientists find molecular trigger that helps prevent aging and disease
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Pivotal study for PSD502 -- the first potential treatment for premature ejaculation
At the annual meeting of the Sexual Medicine Society of North America (SMSNA), Inc. in San Diego, Sciele Pharma, Inc., a Shionogi Company and Plethora Solutions Limited, a wholly owned subsidiary of Plethora Solutions Holdings PLC ("Plethora" - AIM:PLE)., today presented data from its second positive pivotal study of PSD502 for the treatment of premature ejaculation (PE).
Night Beat, Overtime and a Disrupted Sleep Pattern Can Harm Officers' Health
A police officer who works the night shift, typically from 8 p.m. to 4 a.m., already is at a disadvantage when it comes to getting a good "night's" sleep.
Fat collections linked to decreased heart function
Researchers from Boston University School of Medicine (BUSM) have shown that fat collection in different body locations, such as around the heart and the aorta and within the liver, are associated with certain decreased heart functions.
Thoughtful words help couples stay fighting fit
Couples who bring thoughtful words to a fight release lower amounts of stress-related proteins, suggesting that rational communication between partners can ease the impact of marital conflict on the immune system.
Researchers discover mechanism of insulin production that can lead to better treatment for diabetes
How a specific gene within the pancreas affects secretion of insulin has been discovered by researchers from the Hebrew University of Jerusalem, in collaboration with Japanese and American universities.
Playing sport up to the end of pregnancy is healthy for the baby and the mother
Contrary to more conservative customs, exercising up to the end of pregnancy has no harmful effect on the weight or size of the foetus.
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