Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers Gain New Understanding of Diabetes and Kidney Disease: Findings May Lead to Effective New Treatments

24.07.2012
Scientists at Joslin Diabetes Center have identified biological mechanisms by which glucagon-like peptide-1 (GLP-1), a gut hormone, protects against kidney disease, and also mechanisms that inhibit its actions in diabetes.

The findings, which are reported today online by Diabetes, may lead to the development of new therapeutic agents that harness the actions of GLP-1 to prevent the harmful effects of hyperglycemia on renal endothelial cells.

Renal complications, also known as diabetic nephropathy, are one of the most life-threatening complications of diabetes that often lead over time to end-stage renal disease (ESRD). About a half million people in the US – 44 percent of whom are diabetics -- have ESRD, which requires dialysis or kidney transplantation. As a result, investigating the relationship of diabetes to renal dysfunction is a major focus of diabetes research. “We are very eager to develop new treatments for diabetic kidney disease,” says George King, M.D., lead author of the study, and chief scientific officer, head of the Dianne Nunnally Hoppes Laboratory for Diabetes Complications and a professor of medicine at Harvard Medical School.

GLP-1 is an incretin hormone that is produced by the intestine in response to food. GLP-1 increases the secretion of insulin from the pancreas, slows absorption of glucose from the gut, and reduces the action of glucagon – all of which lower glucose levels in the blood. In addition, GLP-1 reduces appetite. The drug, exendin-4 (marketed as Exenatide), which mimics the effects of GLP-1, is used to lower blood glucose in type 2 diabetes.

Recent studies have reported that GLP-1 improves the function of renal endothelial cells (which regulate blood clotting, immune response and blood vessel activity, among other critical functions, and are impaired by insulin resistance) and can prevent some renal pathologies in diabetic rodents. GLP-1 receptors (GLP-1R), which are abundant in the intestine, are also found in the endothelium and kidney.

The Joslin study investigated the effects of GLP-1 in non-diabetic and diabetic mice with an “overexpression” of the enzyme PKCâ (protein kinase C-beta) which is produced in excess when blood glucose is high. Excess PKCâ can lead to diabetes complications, including kidney disease. PKCâ enhances the action of angiotensin II (Ang II), a peptide hormone that affects renal filtration and blood flow and also regulates blood pressure, which increases inflammation and accelerates the progression of kidney damage.

The study looked at the interactions of GLP-1, PKC-beta and ANG II that affect GLP-1’s protective action in renal endothelial cells. “We’ve been interested in diabetic kidney disease for a long time, particularly the role of PKCâ and Ang II in promoting kidney damage,” says Dr. King. “We were interested in investigating how GLP-1 could protect against the effects of hyperglycemia on renal function.”

Josin researchers made two major findings: They identified the mechanisms by which GLP-1 can induce protective actions on the glomerular (renal) endothelial cells by inhibiting the signaling pathway of Ang II and its pro-inflammatory effect; and demonstrated a dual signaling mechanism by which hyperglycemia, via PKCâ activation, can increase Ang II action and inhibit GLP-1’s protective effects by reducing the expression of GLP-1 receptors in the glomerular endothelial cells. “We know that people with diabetes are more sensitive to Ang II; our data suggests one reason why,” says Dr. King.

The results suggest that effective therapeutic agents could be developed to enhance the effects of GLP-1R on the endothelium which may prevent glomerular endothelial dysfunction and slow the progression of diabetic nephropathy. “We now know that increased PKCâ decreases GLP-1R which makes the kidney less responsive to treatment with GLP-1-based drugs. Possible new treatments could combine PKCâ inhibitors with higher doses of GLP-1 agonists. GLP-1 is one potential pharmaceutical that could both lower glucose and minimize the toxic effects of Ang II to lower the risk of kidney diseases,” says Dr. King.

The study was funded by the National Eye Institute (NEI), a component of the National Institutes of Health.

About Joslin Diabetes Center

Joslin Diabetes Center, located in Boston, Massachusetts, is the world's largest diabetes research and clinical care organization. Joslin is dedicated to ensuring that people with diabetes live long, healthy lives and offers real hope and progress toward diabetes prevention and a cure. Joslin is an independent, nonprofit institution affiliated with Harvard Medical School.

Our mission is to prevent, treat and cure diabetes. Our vision is a world free of diabetes and its complications.

For more information , visit www.joslin.org.

Keep up with Joslin research and clinical news at Inside Joslin at www.joslin.org/news/inside_joslin.html.

Become a fan of Joslin on Facebook at www.facebook.com/joslindiabetes.

Follow Joslin on Twitter @JoslinDiabetes.

Jeffrey Bright | Newswise Science News
Further information:
http://www.joslin.org

More articles from Health and Medicine:

nachricht Why might reading make myopic?
18.07.2018 | Universitätsklinikum Tübingen

nachricht Unique brain 'fingerprint' can predict drug effectiveness
11.07.2018 | McGill University

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Metal too 'gummy' to cut? Draw on it with a Sharpie or glue stick, science says

19.07.2018 | Materials Sciences

NSF-supported researchers to present new results on hurricanes and other extreme events

19.07.2018 | Earth Sciences

Scientists uncover the role of a protein in production & survival of myelin-forming cells

19.07.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>