Discovery points to new approach for diabetes therapy

July 12, 2010

CORVALLIS, Ore. - 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 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."
-end-
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.

Oregon State University

Related Diabetes Articles from Brightsurf:

New diabetes medication reduced heart event risk in those with diabetes and kidney disease
Sotagliflozin - a type of medication known as an SGLT2 inhibitor primarily prescribed for Type 2 diabetes - reduces the risk of adverse cardiovascular events for patients with diabetes and kidney disease.

Diabetes drug boosts survival in patients with type 2 diabetes and COVID-19 pneumonia
Sitagliptin, a drug to lower blood sugar in type 2 diabetes, also improves survival in diabetic patients hospitalized with COVID-19, suggests a multicenter observational study in Italy.

Making sense of diabetes
Throughout her 38-year nursing career, Laurel Despins has progressed from a bedside nurse to a clinical nurse specialist and has worked in medical, surgical and cardiac intensive care units.

Helping teens with type 1 diabetes improve diabetes control with MyDiaText
Adolescence is a difficult period of development, made more complex for those with Type 1 diabetes mellitus (T1DM).

Diabetes-in-a-dish model uncovers new insights into the cause of type 2 diabetes
Researchers have developed a novel 'disease-in-a-dish' model to study the basic molecular factors that lead to the development of type 2 diabetes, uncovering the potential existence of major signaling defects both inside and outside of the classical insulin signaling cascade, and providing new perspectives on the mechanisms behind insulin resistance in type 2 diabetes and possibly opportunities for the development of novel therapeutics for the disease.

Tele-diabetes to manage new-onset diabetes during COVID-19 pandemic
Two new case studies highlight the use of tele-diabetes to manage new-onset type 1 diabetes in an adult and an infant during the COVID-19 pandemic.

Genetic profile may predict type 2 diabetes risk among women with gestational diabetes
Women who go on to develop type 2 diabetes after having gestational, or pregnancy-related, diabetes are more likely to have particular genetic profiles, suggests an analysis by researchers at the National Institutes of Health and other institutions.

Maternal gestational diabetes linked to diabetes in children
Children and youth of mothers who had gestational diabetes during pregnancy are at increased risk of diabetes themselves, according to new research published in CMAJ (Canadian Medical Association Journal).

Two diabetes medications don't slow progression of type 2 diabetes in youth
In youth with impaired glucose tolerance or recent-onset type 2 diabetes, neither initial treatment with long-acting insulin followed by the drug metformin, nor metformin alone preserved the body's ability to make insulin, according to results published online June 25 in Diabetes Care.

People with diabetes visit the dentist less frequently despite link between diabetes, oral health
Adults with diabetes are less likely to visit the dentist than people with prediabetes or without diabetes, finds a new study led by researchers at NYU Rory Meyers College of Nursing and East Carolina University's Brody School of Medicine.

Read More: Diabetes News and Diabetes Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.