Anchoring proteins influence glucose metabolism and insulin release

September 4, 2012, European Molecular Biology Organization
The A-kinase anchoring protein is a potential new drug target for diabetes. Credit: John D. Scott & EMBO

Scientists from the United States and Sweden have discovered a new control point that could be important as a drug target for the treatment of diabetes and other metabolic diseases. A-kinase anchoring proteins or AKAPs are known to influence the spatial distribution of kinases within the cell, crucial enzymes that control important molecular events related to the regulation of glucose levels in the blood. In a new study published in The EMBO Journal, the team of researchers led by Simon Hinke and John Scott reveal for the first time that AKAPs influence the levels of glucose in the body by coordinating the spatial positioning of phosphatases, naturally occurring enzymes that counteract the effects of kinase enzymes.

"Our discovery that anchored enzymes contribute to the regulation of cellular events that underlie diabetes may help us to move more rapidly toward new therapies to control this increasingly prevalent metabolic disease," commented John Scott, Edwin G. Krebs–Hilma Speights Professor of Pharmacology at the University of Washington School of Medicine, Seattle and an investigator of the Howard Hughes Medical Institute. "The observation that AKAP 150 functions by coordinating phosphatase activity in the cell reveals a new role for these anchoring proteins in the control of and related metabolic disorders. It also suggests that new drugs that interfere with the role of anchoring proteins are possible therapeutic interventions to treat chronic diseases such as diabetes."

The researchers used imaging techniques as well as genetic modification of isolated insulin-secreting cells and whole mice to investigate the impact of anchoring proteins on glucose metabolism and . Mice that lacked the gene for the AKAP150 anchoring protein produced less insulin from in the islets of Langerhans. However, they coped better with limited amounts of hormone due to increased sensitivity to insulin in the target tissues (skeletal muscle). The scientists showed that these effects are due to a seven-amino-acid sequence in the anchor protein that directly interacts with the surface of the phosphatase enzyme.

The release of insulin is the main way in which the levels of glucose are controlled in the body. If it is possible to develop drugs that target the region where anchoring proteins specifically interact with phosphatase enzymes it is feasible that insulin sensitivity could be improved in selected tissues such as skeletal muscle. This would represent a valuable new molecular control point that might offer clinical benefits for diabetics, individuals with other metabolic disorders and patients who are being treated with immunosuppressive drugs following organ transplantation.

Explore further: Increased muscle mass may lower risk of pre-diabetes

More information: Anchored phosphatases modulate glucose homeostasis, Simon A. Hinke, Manuel F Navedo, Allison Ulman, Jennifer L Whiting, Patrick J Nygren, Geng Tian, Antonio J Jimenez-Caliani, Lorene K Langeberg, Vincenzo Cirulli, Anders Tengholm, Mark L Dell'Acqua, L Fernando Santana, John D Scott, Read the paper: DOI: 10.1038/emboj.2012.244

Related Stories

Increased muscle mass may lower risk of pre-diabetes

July 28, 2011
A recent study accepted for publication in The Endocrine Society's Journal of Clinical Endocrinology & Metabolism (JCEM) found that the greater an individual's total muscle mass, the lower the person's risk of having insulin ...

Investigational diabetes drug may have fewer side effects

June 4, 2012
Drugs for type 2 diabetes can contribute to weight gain, bone fractures and cardiovascular problems, but in mice, an investigational drug appears to improve insulin sensitivity without those troublesome side effects, researchers ...

Recommended for you

More surprises about blood development—and a possible lead for making lymphocytes

January 22, 2018
Hematopoietic stem cells (HSCs) have long been regarded as the granddaddy of all blood cells. After we are born, these multipotent cells give rise to all our cell lineages: lymphoid, myeloid and erythroid cells. Hematologists ...

How metal scaffolds enhance the bone healing process

January 22, 2018
A new study shows how mechanically optimized constructs known as titanium-mesh scaffolds can optimize bone regeneration. The induction of bone regeneration is of importance when treating large bone defects. As demonstrated ...

Researchers illustrate how muscle growth inhibitor is activated, could aid in treating ALS

January 19, 2018
Researchers at the University of Cincinnati (UC) College of Medicine are part of an international team that has identified how the inactive or latent form of GDF8, a signaling protein also known as myostatin responsible for ...

Bioengineered soft microfibers improve T-cell production

January 18, 2018
T cells play a key role in the body's immune response against pathogens. As a new class of therapeutic approaches, T cells are being harnessed to fight cancer, promising more precise, longer-lasting mitigation than traditional, ...

Weight flux alters molecular profile, study finds

January 17, 2018
The human body undergoes dramatic changes during even short periods of weight gain and loss, according to a study led by researchers at the Stanford University School of Medicine.

Secrets of longevity protein revealed in new study

January 17, 2018
Named after the Greek goddess who spun the thread of life, Klotho proteins play an important role in the regulation of longevity and metabolism. In a recent Yale-led study, researchers revealed the three-dimensional structure ...

0 comments

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.