Researchers identify cause of insulin resistance in type 2 diabetics

March 7, 2016, University of Pennsylvania School of Medicine
Blood glucose monitoring. Credit: Wikipedia

More than 29 million Americans are currently living with diabetes. The majority have type 2 diabetes, and for them insulin resistance - their body's inability to effectively process sugar - is a part of daily life. Therefore, understanding the cause of insulin resistance is critical to tackling this chronic disease. A new link between high levels of certain amino acids and type 2 diabetes was found by a team led by researchers from the Perelman School of Medicine at the University of Pennsylvania, using mouse and human muscle and blood samples to evaluate the mechanisms that lead to insulin resistance. The findings of this study appear online in Nature Medicine ahead of the print issue.

For people with type 2 , the problem of insulin resistance means there is plenty of insulin but the body does not respond to it effectively. While most people associate this resistance with sugar levels in the blood, diabetes is also a problem with excess fat, especially too much fat inside skeletal muscle, which leads to the insulin resistance. If the level of fat in muscles can be reduced then, theoretically, insulin resistance can be prevented, surmise investigators.

"This research sought to answer a few large questions," said senior author Zoltan Arany, MD, PhD, an associate professor of Cardiovascular Medicine. "How does fat get into skeletal muscle? And how is the elevation of certain amino acids in people with diabetes related to insulin resistance? We have appreciated for over ten years that diabetes is accompanied by elevations in the blood of branched-chain amino acids, which humans can only obtain in their diet. However, we didn't understand how this could cause insulin resistance and diabetes. How is elevated blood sugar related to these amino acids?"

The team found that a byproduct compound of breakdown of these amino acids, called 3-HIB, is secreted from and activates cells in the vascular wall to transport more fat into tissue. This leads to fat accumulation in the muscle, in turn leading to insulin resistance in mice. Conversely, inhibiting the synthesis of 3-HIB in muscle cells blocked the uptake of fat in muscle.

"In this study we showed a new mechanism to explain how 3-HIB, by regulating the transport of in and out of muscle, links the breakdown of branched-chain amino acids with fatty acid accumulation, showing how increased amino acid flux can cause diabetes," Arany said.

While most of this research was conducted using mouse cells, the team also found that 3-HIB, the byproduct molecule, was elevated in people with type 2 diabetes. Because of this, Arany and colleagues say that more studies are needed to fully examine the nature of this mechanism among people with type 2 diabetes.

"The discovery of this novel pathway - the way the body breaks down these that drives more fat into the muscles - opens new avenues for future research on , and introduces a conceptually entirely new way to target treatment for diabetes" Arany said.

Explore further: Diabetes discovery could lead to more effective drugs

More information: A branched-chain amino acid metabolite drives vascular fatty acid transport and causes insulin resistance, Nature Medicine, DOI: 10.1038/nm.4057

Related Stories

Diabetes discovery could lead to more effective drugs

February 3, 2016
The formation of type 2 diabetes is directly related to how our muscles convert sugar, a landmark new study has found.

Plasma branched-chain amino acids linked to insulin sensitivity

February 24, 2016
(HealthDay)—Plasma branched-chain amino acids (BCAAs) are associated with insulin sensitivity (SI) and metabolic clearance rate of insulin (MCRI), according to a study published online Feb. 19 in Diabetes Care.

Insulin-secreting cells report on insulin resistance

February 22, 2016
Diabetes researchers at Sweden's Karolinska Institutet have developed a novel technique that makes it possible to monitor insulin resistance in a non-invasive manner over time in mice. The new method, presented in the journal ...

Women retain insulin sensitivity better than men

March 17, 2015
It's long been known that obese men are more likely to develop type two diabetes than obese women, but researchers at McMaster University have discovered it may be related to a difference between the sexes in the activity ...

Gastric bypass surgery improves blood sugar handling and insulin sensitivity, study finds

October 5, 2015
Roux-en-Y, the most common type of gastric bypass surgery, can lead to remission of type 2 diabetes along with weight loss. A new study in the American Journal of Physiology—Regulatory, Integrative and Comparative Physiology ...

Saturated fatty acids lead to mitochondrial dysfunction and insulin resistance

January 20, 2012
Excessive levels of certain saturated fatty acids cause mitochondria to fragment, leading to insulin resistance in skeletal muscle, a precursor of type 2 diabetes, according to a paper in the January issue of the journal ...

Recommended for you

Genetic discovery may help better identify children at risk for type 1 diabetes

January 17, 2018
Six novel chromosomal regions identified by scientists leading a large, prospective study of children at risk for type 1 diabetes will enable the discovery of more genes that cause the disease and more targets for treating ...

Thirty-year study shows women who breastfeed for six months or more reduce their diabetes risk

January 16, 2018
In a long-term national study, breastfeeding for six months or longer cuts the risk of developing type 2 diabetes nearly in half for women throughout their childbearing years, according to new Kaiser Permanente research published ...

Women who have gestational diabetes in pregnancy are at higher risk of future health issues

January 16, 2018
Women who have gestational diabetes mellitus (GDM) during pregnancy have a higher than usual risk of developing type 2 diabetes, hypertension, and ischemic heart disease in the future, according to new research led by the ...

Diabetes gene found that causes low and high blood sugar levels in the same family

January 15, 2018
A study of families with rare blood sugar conditions has revealed a new gene thought to be critical in the regulation of insulin, the key hormone in diabetes.

Discovery could lead to new therapies for diabetics

January 12, 2018
New research by MDI Biological Laboratory scientist Sandra Rieger, Ph.D., and her team has demonstrated that an enzyme she had previously identified as playing a role in peripheral neuropathy induced by cancer chemotherapy ...

Enzyme shown to regulate inflammation and metabolism in fat tissue

January 11, 2018
The human body has two primary kinds of fat—white fat, which stores excess calories and is associated with obesity, and brown fat, which burns calories in order to produce heat and has garnered interest as a potential means ...

6 comments

Adjust slider to filter visible comments by rank

Display comments: newest first

Shootist
1 / 5 (1) Mar 07, 2016
Type II diabetic?

Don't eat more than 20-40 carbohydrates a day until you reach your ideal body weight.

Discover you're no longer diabetic.
tekram
not rated yet Mar 07, 2016
Diabetic state is more than just hyperglycemia.

Not only hyperglycemia and dyslipidemia, but also amino acids (AAs) derangement is a characteristic part of the diabetic state that might play a pathogenic role. The underlying mechanisms of the relationship of BCAAs to type 2 diabetes severity, progression or prediction remain to be defined. BCAAs metabolic pathways could also serve as potential targets for the treatment of type 2 diabetes.
IronhorseA
not rated yet Mar 08, 2016
Avoid or limit foods high in branched chain amino acids.
Sarah_Belle
Mar 09, 2016
This comment has been removed by a moderator.
joel532
Mar 09, 2016
This comment has been removed by a moderator.
frankfv8
1 / 5 (1) Apr 03, 2016
they did say "conceptually" without the proper amino acids & minerals diabetes can not be overcome . that's factual and no synthetic's or rock hard minerals only from a plant for immediate use , we have them aminospus.com

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.