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 Rabies viruses reveal wiring in transparent brains
19.01.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht On track to heal leukaemia
18.01.2017 | Universitätsspital Bern

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: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

New Study Will Help Find the Best Locations for Thermal Power Stations in Iceland

19.01.2017 | Earth Sciences

Not of Divided Mind

19.01.2017 | Life Sciences

Molecule flash mob

19.01.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>