Diabetes complications rooted in faulty cell repairJanuary 26, 2006
UF researchers restore vitality to cells in lab experiments
University of Florida researchers say primitive cells that act like molecular maintenance men-traveling throughout the body to repair damaged blood vessels-become too rigid to move in patients with diabetes, fueling the disease's vascular complications. But they have found a way to restore the cells' flexibility, at least in the laboratory, according to findings published in the January issue of the journal Diabetes.
Having diabetes markedly raises the risk of developing a host of other ailments, from heart disease to stroke, blindness and kidney failure. Many arise after blood vessels suffer damage, spurring the accumulation of fatty deposits in the arteries or the wild, blinding growth of capillaries in the eye.
"We're interested in what happens in the body at the molecular level to cause these life-threatening problems," said Mark S. Segal, Ph.D., an assistant professor of nephrology, hypertension and transplantation at UF's College of Medicine. "Our work is focused on understanding why diabetic patients are at increased risk for these other diseases."
The problem is rooted in the body's response to vascular injury. The bone marrow churns out cells crucial to repairing the damaged lining of blood vessels. But sometimes they fail to report for duty.
"Part of the defect we think is occurring in diabetic patients is these cells do not carry out appropriate repair, and therefore these patients are at higher risk for cardiovascular disease and other complications," Segal said.
The inability of the cells to repair the peripheral vasculature, the large vessels of the body, is similar to their inability to repair the small vessels within the eye, he added.
"In the vasculature it leads to atherosclerosis, and within the eye it leads to diabetic retinopathy," he said. "So the link is we have one defect in these cells that can lead to both of these problems."
UF researchers isolated these repair cells from blood samples drawn from patients with diabetes and chronic kidney disease and studied them in the laboratory. The cells were unable to move about normally. But when nitric oxide gas was added, Segal said, the cells lost their rigidity, becoming suppler, and their ability to move dramatically improved.
In the body, nitric oxide occurs naturally. It helps the repair cells move out of the bone marrow where they are made, and it opens blood vessels and improves the uptake of oxygen. Patients with diabetes, however, commonly have low levels of nitric oxide.
"We went on to show that actually what's happening is nitric oxide is affecting the skeleton, or scaffold of the cell, and by adding nitric oxide we're able to rearrange the scaffold," Segal said. "When we rearrange the scaffold, the cells are able to migrate. The benefit of this is that when cells have improved movement they are able to repair the endothelium (the lining of the blood vessels) better and perhaps prevent atherosclerosis."
UF scientists suspect that in the cells taken from diabetic patients, nitric oxide interacts with a protein that steers the protein to the cell surface instead of inserting it into the cell as it would in healthy people. That causes the cell to stiffen.
The finding raises the possibility that nitric oxide could someday be used to keep the cells mobile, enabling them to travel to distant sites when needed, Segal said.
"The importance of this is related to other work that has shown that many drugs being used on the market today actually affect nitric oxide levels within these cells," Segal said. "So someday there may be two ways to help people whose cells may not function as well as they should. One is through certain medications-there may be a way we could actually give medications that would affect the nitric oxide levels within these cells and enhance their migratory ability. The other is through certain instances where we might actually collect these cells, treat them with nitric oxide outside the body and give them back to patients, to help improve the cells' migration ability."
In the future, for example, patients with diabetes and atherosclerosis who require angioplasty might receive injections of their own repair cells. The cells would be removed, incubated with nitric oxide to improve their function and then returned. They would theoretically help blood vessels heal more quickly, and perhaps keep new fatty deposits from forming, Segal speculated.
The research grew out of previous work at UF in collaboration with UF biochemist Daniel Purich, Ph.D., and pharmacologist Maria Grant, M.D. UF materials scientist Roger Tran-Son-Tay, Ph.D., among others, also participated in the current study.
"The work of Segal and colleagues is groundbreaking and provides important insights into the underlying mechanism of blood vessel damage in diabetes, which is the hallmark lesion for complications affecting the kidneys, eyes and nerves in patients with diabetes," said Anupam Agarwal, M.D., director of the Nephrology Research and Training Center at the University of Alabama at Birmingham.
University of Florida
Related Diabetes Current Events and Diabetes News Articles
Leaky blood-brain barrier linked to Alzheimer's disease
Researchers using contrast-enhanced MRI have identified leakages in the blood-brain barrier (BBB) of people with early Alzheimer's disease (AD), according to a new study published online in the journal Radiology.
Researchers suggest whole-person perspective is needed to assess obesity
Authors from the Cleveland Clinic's Bariatric and Metabolic Institute recommend physicians use obesity staging models to recognize and manage weight-related health issues that may not be captured by traditional diagnosis criteria.
Autism care improved, diagnosis time shortened by new MU program
Wait lists for a specialist to confirm an autism diagnosis can be agonizing and last months. As the prevalence of autism and autism spectrum disorders increase, so does the demand for a health care system that is fully equipped to respond to the complex needs associated with autism.
Novel type 2 diabetes risk model more accurately assesses disease trajectory
An innovative model for determining a person's risk of developing type 2 diabetes (T2D) overcomes many of the challenges associated with estimating the onset of a chronic condition based on the usual sequence of comorbid conditions that lead up to a diagnosis of T2D.
Newly discovered gene regulates hyperglycemia-induced beta cell death in type 2 diabetes
It's no secret that over time, elevated levels of blood glucose (hyperglycemia) can induce the death of the pancreatic beta cells.
Study show female heart patients less likely to get blood thinning therapy
Female atrial fibrillation patients are less likely than their male counterparts to receive blood thinning therapies to prevent stroke, say University of Cincinnati College of Medicine researchers.
Ancient anti-inflammatory drug salicylic acid has cancer-fighting properties
Scientists from the Gladstone Institutes have identified a new pathway by which salicylic acid--a key compound in the nonsteroidal anti-inflammatory drugs aspirin and diflunisal--stops inflammation and cancer.
New study uncovers mechanisms underlying how diabetes damages the heart
Cardiac complications are the number one cause of death among diabetics. Now a team of scientists has uncovered a molecular mechanism involved in a common form of heart damage found in people with diabetes.
PNNL helps lead national microbiome initiative
Scientists at the U.S. Department of Energy's Pacific Northwest National Laboratory are playing a central role as the nation devotes more than $500 million to understand communities of microorganisms and their role in climate science, food production and human health.
Study finds one third of children have higher levels of cardiometabolic risk factors due to family history
A new study published in Diabetologia (the journal of the European Association for the Study of Diabetes [EASD]) shows that children with a strong family history of cardiovascular disease (CVD) and/or type 2 diabetes were found to have cholesterol levels significantly higher than children with no family history of those conditions.
More Diabetes Current Events and Diabetes News Articles