Nutrition experts at Oregon State University have essentially “cured” laboratory mice of mild, diet-induced diabetes by stimulating the production of a particular enzyme.
The findings could offer a new approach to diabetes therapy, experts say, especially if a drug could be identified that would do the same thing, which in this case was accomplished with genetic manipulation.
Increased levels of this enzyme, called fatty acid elongase-5, restored normal function to diseased livers in mice, restored normal levels of blood glucose and insulin, and effectively corrected the risk factors incurred with diet-induced diabetes.
“This effect was fairly remarkable and not anticipated,” said Donald Jump, a professor of nutrition and exercise sciences in the College of Health and Human Sciences at Oregon State, where he is an expert on lipid metabolism and principal investigator with OSU’s Linus Pauling Institute.
“It doesn’t provide a therapy yet, but could be fairly important if we can find a drug to raise levels of this enzyme,” Jump said. “There are already some drugs on the market that do this to a point, and further research in the field would be merited.”
The studies were done on a family of enzymes called “fatty acid elongases,” which have been known of for decades. Humans get essential fatty acids that they cannot naturally make from certain foods in their diet. These essential fatty acids are converted to longer and more unsaturated fatty acids. The fatty acid end products of these reactions are important for managing metabolism, inflammation, cognitive function, cardiovascular health, reproduction, vision and other metabolic roles.
The enzymes that do this are called fatty acid elongases, and much has been learned in recent years about them. In research on diet-induced obesity and diabetes, OSU studied enzyme conversion pathways, and found that elongase-5 was often impaired in mice with elevated insulin levels and diet-induced obesity.
The scientists used an established system, based on a recombinant adenovirus, to import the gene responsible for production of elongase-5 into the livers of obese, diabetic mice. When this “delivery system” began to function and the mice produced higher levels of the enzyme, their diet-induced liver defects and elevated blood sugar disappeared.
“The use of a genetic delivery system such as this was functional, but it may not be a permanent solution,” Jump said. “For human therapy, it would be better to find a drug that could accomplish the same thing, and that may be possible. There are already drugs on the market, such as some fibrate drugs, that induce higher levels of elongase-5 to some extent.”
There are also drugs used with diabetic patients that can lower blood sugar levels, Jump said, but some have side effects and undesired complications. The potential for raising levels of elongase-5 would be a new, specific and targeted approach to diabetes therapy, he said. While lowering blood sugar, the elevated levels of elongase-5 also reduced triglycerides in the liver, another desirable goal. Elevated triglycerides are associated with “fatty liver,” also known as non-alcoholic fatty liver disease. This can progress to more severe liver diseases such as fibrosis, cirrhosis and cancer.
Further research is needed to define the exact biological mechanisms at work in this process, and determine what the fatty acids do that affects carbohydrate and triglyceride metabolism, he said. It appears that high fat diets suppress elongase-5 activity.
“These studies establish a link between fatty acid elongation and hepatic glucose and triglyceride metabolism,” the researchers wrote in their report, “and suggest a role for regulators of elongase-5 activity in the treatment of diet-induced hyperglycemia and fatty liver.”
The study was published in the Journal of Lipid Research. The research was supported by the National Institutes of Health and the National Institute for Food and Agriculture of the U.S. Department of Agriculture.
By David Stauth, OSU News and Communications
16 replies on “Discovery points to new approach for diabetes therapy”
Is it possible to stimulate the enzyme production without using a drug? So many drugs have side effects that aren[t even known when the drug is approved; the side effects seem to show up later — when it may be too late or with too many complications.
Can work be done with natural processes?
We are still in an early stage in this research. One line of investigation is to determine if certain dietary supplements can have the same effect on blood glucose & fatty liver as seen when we over expresss fatty acid elongase-5 in liver.
I am 58 and have type 2 dieabeties I am vary interested in this!
I have been a Type 2 dieabetic for quite some time. When I last visited my doctor she reduced my medication because I lost some weight. I am very interested in this news. Please keep me informed. Thank you.
Please send me any more information you may get. I am on insulin and have no energy at all. I am 70 years old. I can’t walk up the stairs. Thank you
Great news. Thank you for your research. Is there anyway to follow the results of your research as it proceeds? Is there any way the public can help? Like write our Senators and Representatives and NIH requesting support your program?
Dear Dr Jump, et al
My husband and I are very interested in your research. In addition to diabetes, I have diagnosed low cellular metabolism as measured through the TCA cycle.
I’d be interested to know if your research has any noticeable impact on cellular metabolism rates.
Your news/research was fantastic to hear…Thank you so very much for sharing. One step closer.
Awesome news! But one point for clarification.
When this becomes a viable cure (hopefully soon) would a person be able to go back to a normal diet?
I ask because I know quite a few people who are not overweight and active but have still developed Type ii. For these people diabetes feels like a punishment.
Thank you for your interest and comments. We will keep you informed as new developments occur. Writing to your senators and representatives encouraging them to provide more support to the NIH is alwasy a good strategy.
Here are responses to comments #7 & 8.
#7: Yes, we have recently carried out studies to look at TCA metabolites and have seen significant effects on key metabolites. The changes we see may be related to the elongase-5-mediated suppression of hepatic glucose production and blood glucose levels. These results, however, are still preliminary.
#8: Your question is a good one. We do not have enough information yet to give a definitive answer. We will need to look at models of NIDDM that are not linked to obesity.
I have been recently diagnosed with type two diabetes.. I’m scared thru the roof! I am overweight and have begun to diet. I’m not on any pill since I have been managing it thru dieting. My question is apart from the research you are doing which is great and If so you definitely should have a nobel prize, but is there something extra I can do to get rid of the fat in the liver in order to help my diabetes?
This story has given me hope!
hope you conquer this!
Your physician (internist, diabetologist, etc) should have provided you with information on modifications to your diet. In general, these modifications include decrease in total calories and lower total fat in the diet. Increasing polyunsaturated fat, particularly omega-3 fatty acids are beneficial. In addition, your physician should have recommended an exercise routine,one that does not put you at risk. Together, modification of diet and increased exercise, are the first best steps in managing or reversing the diabetes. Visit the website for the American Diabetes association (www.diabetes.org). This site provides useful information of diet and exercise for the T2D patient.
This will be really great news.I have recently been diagnosed with type 2 diabetes at 30 years which was very shocking to me..been very active all my life playing semi pro football,soccar..But I Reduced my training intensity for six months after an injury and thats when I got diabetes..just want to know,will this be a one time cure or will the patient have to continue taking medication for the rest of his life?
Thank you, Professor Jump for personally responding. At age 58, very active, I just got diagnosed with T2D. I am flabbergasted. Though the BMI index says I’m overweight, I’m built like Schwarznagger, so didn’t seem so. I’ve heavily modified my diet and am losing weight. Doctor Jump, what might be the timeline for some sort of therapy? Could we sign up as you test the procedure on live patients?
We do not have a therapy yet; we are still working on the mechanism. So, we will not be doing work with humans soon.
Regarding the T2D, losing weight and exercising is a good strategy. The goal is to get your fasting blood glucose down to a normal level.
Dear Prof Jump, wishing you and your team every success in your ongoing research efforts to one day (hopefully) assist people to better address T2D. I’m just wondering please, if you remain “encouraged” by the results you are achieving as your work continues? Thank you.