Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cystic fibrosis disrupts pancreas two ways in CF-related diabetes

18.09.2012
A new University of Iowa study suggests there are two root causes of a type of diabetes associated with cystic fibrosis (CF). The findings, which already have sparked a clinical trial, may guide development of new treatments or even help prevent diabetes in patients with CF.

Almost half of patients with CF will develop diabetes by age 30 and almost one quarter will develop it in their teens. In addition to the health problems caused by high blood sugar, diabetes also worsens lung disease and increases the risk of dying for people with CF. However, the underlying cause of CF-related diabetes is not well understood, and differs from the causes of type 1 or type 2 diabetes.


A new University of Iowa study suggests there are two root causes of a type of diabetes associated with cystic fibrosis (CF). Using a ferret model of CF, the study shows that CF progressively damages the pancreas, disrupting insulin production. More surprisingly, the study also found that CF disrupts the pancreas' insulin-producing islet cells from birth, well before the physical damage occurs. The image shows a confocal 3D rendering of an isolated CF ferret islet stained for insulin (red), glucagon (green), and DAPI nuclear stain (blue), superimposed over a background ferret pancreas section similarly stained for the same antigens.

Credit: University of Iowa

Using a new animal model of CF, the study found two abnormalities that affect the pancreas, the organ that produces insulin, which controls blood sugar levels. The study shows that CF progressively damages the pancreas, disrupting insulin production. More surprisingly, the study also found that CF disrupts the pancreas' insulin production even before the physical damage occurs. The results were published Sept. 17 in the Journal of Clinical Investigation.

Ferrets used to study CF-related diabetes

The UI team studied ferrets with CF that were recently developed in the lab of John Engelhardt, Ph.D., professor and head of anatomy and cell biology at the UI Carver College of Medicine.

"We turned to ferrets because studies in humans and mice have been unable to determine the underlying cause of many CF complications, including diabetes," Engelhardt says. "We found that ferrets with CF, just like humans, spontaneously develop diabetes leaving them unable to prevent high blood sugar levels following a meal."

In humans, CF damages the pancreas, which reduces insulin production. The researchers, including lead authors Alicia Olivier, Ph.D., UI assistant professor of pathology, and Yaling Yi and Xingshen Sun, Ph.D., from Engelhardt's lab, found that CF ferrets developed diabetes at 1-2 months of age, the same age the ferrets experienced severe damage to the pancreas.

"This finding fits well with the long-held view that CF-related diabetes stems from physical damage to the pancreas, which limits the amount of insulin the pancreas can produce," says study co-leader Andrew Norris, M.D., Ph.D., associate professor of pediatrics and biochemistry.

Engelhardt and Norris also are members of the Fraternal Order of Eagles Diabetes Research Center at UI.

CF disrupts insulin production from birth

However, studies in newborn CF ferrets led to an interesting twist in the team's findings. The pancreas in newborn ferrets is essentially healthy, so the team expected normal insulin levels and normal blood sugar regulation. Instead, newborn CF ferrets were unable to control spikes in blood sugar. The study showed that this was because the pancreas in these animals did not secrete the appropriate amount of insulin in response to a spike in blood sugar.

Further investigation homed in on groups of cells with the pancreas -- called islets -- as the source of the problem. Islets are the body's insulin-producing factories. The researchers found that islets from newborn CF ferrets did not secrete insulin normally.

"The finding of abnormal sugar-regulated insulin secretion by isolated CF islets demonstrates for the first time that some of the problems that lead to diabetes in CF patients likely reside within cells of the islet," Engelhardt says.

Likening the CF defect in islets to a broken sugar-thermometer, Engelhardt adds, "CF islets fail to adequately sense changes in sugar and this leads to poorly regulated insulin production."

Although the cellular mechanism for this abnormality is not yet known, findings suggest that the chloride channel protein, which is defective in CF, may directly or indirectly control insulin secretion by the islet.

"This indicates that CF causes a second problem which underlies diabetes, separate from pancreatic structural damage," Norris says. "Ultimately, this research will allow us to determine the major root causes of CF-related diabetes, and may help guide development of new therapies and preventative strategies."

Human studies

The new findings already have generated clinical interest in studying the early changes that occur in insulin regulation in infants and young children with CF. Katie Larson Ode, M.D., clinical assistant professor of pediatrics with UI Children's Hospital, and Toni Moran, M.D., at University of Minnesota, have started a clinical trial to study these abnormalities. Additionally, Engelhardt and Norris have teamed up with Aliye Uc, M.D., UI associate professor of pediatrics, to leverage her expertise on pancreatic damage in ongoing studies of animals with CF.

"Although these studies are focused on cystic fibrosis, future insights into how the cystic fibrosis chloride channel functions to regulate insulin secretion may also lead to better treatments for type 2 and other forms of diabetes," Norris concludes.

The study was funded by grants from the National Institutes of Health and the Fraternal Order of Eagles Diabetes Research Center at UI. Additionally, the studies have indirectly benefited from the funding from the Cystic Fibrosis Foundation that was key in generating the CF ferret model.

Jennifer Brown | EurekAlert!
Further information:
http://www.uiowa.edu

More articles from Life Sciences:

nachricht Repairing damaged hearts with self-healing heart cells
22.08.2017 | National University Health System

nachricht Biochemical 'fingerprints' reveal diabetes progression
22.08.2017 | Umea University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Cholesterol-lowering drugs may fight infectious disease

22.08.2017 | Health and Medicine

Meter-sized single-crystal graphene growth becomes possible

22.08.2017 | Materials Sciences

Repairing damaged hearts with self-healing heart cells

22.08.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>