Cystic fibrosis disrupts pancreas two ways in CF-related 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
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.
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
"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."
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.
Journal reference: Journal of Clinical Investigation
Provided by University of Iowa
- Growth defects in cystic fibrosis may start before birth Nov 09, 2010 | not rated yet | 0
- Mucous breakthrough in mice holds promise for cystic fibrosis Jul 29, 2008 | not rated yet | 0
- Early cystic fibrosis lung disease detected by bronchoalveolar lavage and lung clearance index Jan 27, 2012 | not rated yet | 0
- Cystic fibrosis makes airways more acidic, reduces bacterial killing Jul 04, 2012 | not rated yet | 0
- Pigs provide clues on cystic fibrosis lung disease Apr 28, 2010 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
question on coriolis effect with drag force
2 hours ago I really need help with this question. A small floating object initially moves with velocity v on the surface of a liquid at latitude λ. The...
Question of reflection and transmission of TEM wave in normal incidenc
7 hours ago Suppose TEM wave in +z normal to a boundary on xy plane at z=0. We know *E* & *H* are tangential to the boundary. Let ##\vec E_i=\hat x E##, be the...
the rudyak-krasnolutski effective potencial
8 hours ago Hi ... anyone now how to calculate or the formula of the rudyak-krasnolutski EFFECTIVE potencial ? the effective potencial includes the angular...
Normal force for a lever model
9 hours ago My model is a lever on a table top. One arm is horizontal on the table, while the other arm is raised at an angle alpha. I'm assuming the weight of...
gravity is std. therefore can we rate a 'mass at height' by watts?
15 hours ago For example.... wind turbines are primarily listed by their wattage (1.5MW etc.) Presumably their output is varied according to rotational speed, so...
Calculating on-axis elements of a solenoid
May 22, 2013 I wanted to mention that this solenoid has many winds over many layers. The thickness of the windings is 2.4 inches coming off of the engineering...
- More from Physics Forums - Classical Physics
More news stories
(HealthDay)—Type 2 diabetes is more aggressive in children than adults, with signs of serious complications seen just a few years after diagnosis, new research finds.
Diabetes 3 hours ago | not rated yet | 0
Treatment with high potency statins (especially atorvastatin and simvastatin) may increase the risk of developing diabetes, suggests a paper published today in BMJ.
Diabetes 5 hours ago | not rated yet | 0
Ethnic background plays a surprisingly large role in how diabetes develops on a cellular level, according to two new studies led by researchers at the Stanford University School of Medicine.
Diabetes 8 hours ago | not rated yet | 0 |
Widely-used fish oil supplements modestly increase amounts of a hormone that is associated with lower risk of diabetes and heart disease, according to a study accepted for publication in The Endocrine Society's Journal of ...
Diabetes May 22, 2013 | 5 / 5 (2) | 1
Study shows that women who smoke during pregnancy increase the risk of both obesity and gestational diabetes in their da
Women who smoke during pregnancy increase the risk of both obesity and gestational diabetes, in their daughters, concludes research published in Diabetologia, the journal of the European Association for the Study of Diabet ...
Diabetes May 20, 2013 | not rated yet | 0
High blood glucose is associated with poor outcomes in hospitalized patients, and use of intensive insulin therapy (IIT) to control hyperglycemia is a common practice in hospitals. But the recent evidence does not show a ...
15 minutes ago | not rated yet | 0
(Medical Xpress)—Regulating the distribution of power in neurons is done by a system that makes the national electric grid look simple by comparison. Each neuron has several thousand mitochondria confined ...
6 hours ago | 4.8 / 5 (5) | 0 |
Teams of highly respected Alzheimer's researchers failed to replicate what appeared to be breakthrough results for the treatment of this brain disease when they were published last year in the journal Science.
10 hours ago | 5 / 5 (1) | 2 |
A brief visual task can predict IQ, according to a new study. This surprisingly simple exercise measures the brain's unconscious ability to filter out visual movement. The study shows that individuals whose ...
12 hours ago | 4.9 / 5 (8) | 0 |
Scientists at the National Institutes of Health report they have discovered in mouse studies that a small molecule released in the spinal cord triggers a process that is later experienced in the brain as ...
10 hours ago | 5 / 5 (2) | 0 |
Little is known about why asthma develops, how it constricts the airway or why response to treatments varies between patients. Now, a team of researchers at Weill Cornell Medical College, Columbia University Medical Center ...
10 hours ago | not rated yet | 0 |