Posts tagged Type II diabetes

Improved thinking. Decreased appetite. Lowered blood pressure. The potential health benefits of dark chocolate keep piling up, and scientists are now homing in on what ingredients in chocolate might help prevent obesity, as well as type-2 diabetes. They found that one particular type of antioxidant in cocoa prevented laboratory mice from gaining excess weight and lowered their blood sugar levels. The report appears in ACS’ Journal of Agricultural & Food Chemistry.

Andrew P. Neilson and colleagues explain that cocoa, the basic ingredient of chocolate, is one of the most flavanol-rich foods around. That’s good for chocolate lovers because previous research has shown that flavanols in other foods such as grapes and tea can help fight weight gain and type-2 diabetes. But not all flavanols, which are a type of antioxidant, are created equal. Cocoa has several different kinds of these compounds, so Neilson’s team decided to tease them apart and test each individually for health benefits.

The scientists fed groups of mice different diets, including high-fat and low-fat diets, and high-fat diets supplemented with different kinds of flavanols. They found that adding one particular set of these compounds, known as oligomeric procyanidins (PCs), to the food made the biggest difference in keeping the mice’s weight down if they were on high-fat diets. They also improved glucose tolerance, which could potentially help prevent type-2 diabetes. “Oligomeric PCs appear to possess the greatest antiobesity and antidiabetic bioactivities of the flavanols in cocoa, particularly at the low doses employed for the present study,” the researchers state.

(Source: acs.org)

Researchers from the University of Illinois at Chicago College of Medicine have found that dysfunction in a single gene in mice causes fasting hyperglycemia, one of the major symptoms of type 2 diabetes. Their findings were reported online in the journal Diabetes.

If a gene called MADD is not functioning properly, insulin is not released into the bloodstream to regulate blood sugar levels, says Bellur S. Prabhakar, professor and head of microbiology and immunology at UIC and lead author of the paper.

Type 2 diabetes affects roughly 8 percent of Americans and more than 366 million people worldwide. It can cause serious complications, including cardiovascular disease, kidney failure, loss of limbs and blindness.

In a healthy person, beta cells in the pancreas secrete the hormone insulin in response to increases in blood glucose after eating. Insulin allows glucose to enter cells where it can be used as energy, keeping glucose levels in the blood within a narrow range. People with type 2 diabetes don’t produce enough insulin or are resistant to its effects. They must closely monitor their blood glucose throughout the day and, when medication fails, inject insulin.

In previous work, Prabhakar isolated several genes from human beta cells, including MADD, which is also involved in certain cancers. Small genetic variations found among thousands of human subjects revealed that a mutation in MADD was strongly associated with type 2 diabetes in Europeans and Han Chinese.

People with this mutation had high blood glucose and problems of insulin secretion – the “hallmarks of type 2 diabetes,” Prabhakar said. But it was unclear how the mutation was causing the symptoms, or whether it caused them on its own or in concert with other genes associated with type 2 diabetes.

To study the role of MADD in diabetes, Prabhakar and his colleagues developed a mouse model in which the MADD gene was deleted from the insulin-producing beta cells. All such mice had elevated blood glucose levels, which the researchers found was due to insufficient release of insulin.

“We didn’t see any insulin resistance in their cells, but it was clear that the beta cells were not functioning properly,” Prabhakar said. Examination of the beta cells revealed that they were packed with insulin. “The cells were producing plenty of insulin, they just weren’t secreting it,” he said.

The finding shows that type 2 diabetes can be directly caused by the loss of a properly functioning MADD gene alone, Prabhakar said. “Without the gene, insulin can’t leave the beta cells, and blood glucose levels are chronically high.”

Prabhakar now hopes to investigate the effect of a drug that allows for the secretion of insulin in MADD-deficient beta cells.

“If this drug works to reverse the deficits associated with a defective MADD gene in the beta cells of our model mice, it may have potential for treating people with this mutation who have an insulin-secretion defect and/or type 2 diabetes,” he said.

(Source: news.uic.edu)

High blood-sugar levels, such as those linked with Type 2 diabetes, make beta amyloid protein associated with Alzheimer’s disease dramatically more toxic to cells lining blood vessels in the brain, according to a new Tulane University study published in latest issue of the Journal of Alzheimer’s Disease.

The study supports growing evidence pointing to glucose levels and vascular damage as contributors to dementia.

“Previously, it was believed that Alzheimer’s disease was due to the accumulation of ‘tangles’ in neurons in the brain from overproduction and reduced removal of beta amyloid protein,” said senior investigator Dr. David Busija, regents professor and chair of pharmacology at Tulane University School of Medicine. “While neuronal involvement is a major factor in Alzheimer’s development, recent evidence indicates damaged cerebral blood vessels compromised by high blood sugar play a role. Even though the links among Type 2 diabetes, brain blood vessels and Alzheimer’s progression are unclear, hyperglycemia appears to play a role.”

Drs. Cristina Carvalho and Paula Moreira from the University of Coimbra in Portugal were co-investigators in the study.  

Researchers studied cell cultures taken from the lining of cerebral blood vessels, one from normal rats and another from mice with uncontrolled chronic diabetes. They exposed the cells to beta amyloid and different levels of glucose and later measured their viability. Cells exposed to high glucose or beta amyloid alone showed no changes in viability. However, when exposed to hyperglycemic conditions and beta amyloid, viability decreased by 40 percent. Researchers suspect the damage is due to oxidative stress from the mitochondria of the cell.

The cells from diabetic mice were more susceptible to damage and death to beta amyloid protein − even at normal glucose levels. The increased toxicity of beta amyloid may damage the blood-brain barrier, disrupt normal blood flow to the brain and decrease clearance of beta amyloid protein.

The study’s findings underscore the need to aggressively control blood sugar levels in diabetic individuals, Busija said.

(Source: tulane.edu)

Researchers at NYU Langone Medical Center have discovered a mechanism that triggers chronic inflammation in Alzheimer’s, atherosclerosis and type-2 diabetes. The results, published today in Nature Immunology, suggest a common biochemical thread to multiple diseases and point the way to a new class of therapies that could treat chronic inflammation in these non-infectious diseases without crippling the immune system. Alzheimer’s, atherosclerosis and type-2 diabetes—diseases associated with aging and inflammation—affect more than 100 million Americans.

When the body encounters a pathogen, it unleashes a rush of chemicals known as cytokines that draws immune cells to the site of infection and causes inflammation. Particulate matter in the body, such as the cholesterol crystals associated with vascular disease and the amyloid plaques that form in the brain in Alzheimer’s disease, can also cause inflammation but the exact mechanism of action remains unclear. Researchers previously thought that these crystals and plaques accumulate outside of cells, and that macrophages—immune cells that scavenge debris in the body—induce inflammation as they attempt to clear them.

“We’ve discovered that the mechanism causing chronic inflammation in these diseases is actually very different,” says Kathryn J. Moore, PhD, senior author of the study and associate professor of medicine and cell biology, Leon H. Charney Division of Cardiology at NYU Langone Medical Center.

The researchers found that particulate matter does not linger on the outside of cells. Instead, a receptor called CD36 present on macrophages draws the soluble forms of these particles inside the cell where they are transformed into substances that trigger an inflammatory response. Says Dr. Moore, “What we found is that CD36 binds soluble cholesterol and protein matter associated with these diseases, pulls them inside the cell, and then transforms them. The resulting insoluble crystals and amyloid damage the macrophage and trigger a powerful cytokine, called interleukin-1B, linked to a chronic inflammatory response.”

These findings hold exciting clinical implications.When the researchers blocked the CD36 receptor in mice with atherosclerosis (in which cholesterol thickens the arteries), the cytokine response declined, fewer cholesterol crystals formed in plaques, and inflammation decreased. Consequently, atherosclerosis also abated.

Other less-targeted strategies to control inflammation may hamper the immune response, but the CD36 strategy spares certain cytokines to fight off pathogens, while blocking CD36’s ability to trigger interleukin-1B.

“Our findings identify CD36 as a central regulator of the immune response in these conditions and suggest that blocking CD36 might be a common therapeutic option for all three diseases,” says Dr. Moore.

(Source: communications.med.nyu.edu)

A protein secreted with insulin travels through the bloodstream and accumulates in the brains of individuals with type 2 diabetes and dementia, in the same manner as the amyloid beta (Αβ) plaques that are associated with Alzheimer’s disease, a study by researchers with the UC Davis Alzheimer’s Disease Center has found.

The study is the first to identify deposits of the protein, called amylin, in the brains of people with Alzheimer’s disease, as well as combined deposits of amylin and Aβ plaques, suggesting that amylin is a second amyloid as well as a new biomarker for age-related dementia and Alzheimer’s.

“We’ve known for a long time that diabetes hurts the brain, and there has been a lot of speculation about why that occurs, but there has been no conclusive evidence until now,” said UC Davis Alzheimer’s Disease Center Director Charles DeCarli.

“This research is the first to provide clear evidence that amylin gets into the brain itself and that it forms plaques that are just like the amyloid beta that has been thought to be the cause of Alzheimer’s disease,” DeCarli said. “In fact, the amylin looks like the amyloid beta protein, and they both interact. That’s why we’re calling it the second amyloid of Alzheimer’s disease.”

 ”Amylin deposition in the brain: A second amyloid in Alzheimer’s disease?” is published online today in the Annals of Neurology.

Type 2 diabetes is a chronic metabolic disorder that increases the risk for cerebrovascular disease and dementia, a risk that develops years before the onset of clinically apparent diabetes. Its incidence is far greater among people who are obese and insulin resistant.

Amylin, or islet amyloid polypeptide, is a hormone produced by the pancreas that circulates in the bloodstream with insulin and plays a critical role in glycemic regulation by slowing gastric emptying, promoting satiety and preventing post-prandial spikes in blood glucose levels. Its deposition in the pancreas is a hallmark of type 2 diabetes.

When over-secreted, some proteins have a higher propensity to stick to one another, forming small aggregates, called oligomers, fibrils and amyloids. These types of proteins are called amyloidogenic and include amylin and Aβ. There are about 28 amyloidogenic proteins, each of which is associated with diseases.                

The study was conducted by examining brain tissue from individuals who fell into three groups: those who had both diabetes and dementia from cerebrovascular or Alzheimer’s disease; those with Alzheimer’s disease without diabetes; and age-matched healthy individuals who served as controls.

The research found numerous amylin deposits in the gray matter of the diabetic patients with dementia, as well as in the walls of the blood vessels in their brains, suggesting amylin influx from blood circulation. Surprisingly, the researchers also found amylin in the brain tissue of individuals with Alzheimer’s who had not been diagnosed with diabetes; they postulate that these individuals may have had undiagnosed insulin resistance. They did not find amylin deposits in the brains of the healthy control subjects.

“We found that the amylin deposits in the brains of people with dementia are both independent of and co-located with the Aβ, which is the suspected cause of Alzheimer’s disease,” said Florin Despa, assistant professor-in-residence in the UC Davis Department of Pharmacology. “It is both in the walls of the blood vessels of the brain and also in areas remote from the blood vessels.

“It is accumulating in the brain and we found signs that amylin is killing neurons similar to Aβ,” he continued. “And that might be the answer to the question of ‘What makes obese and type 2 diabetes patients more prone to developing dementia?’”

The researchers undertook the investigation after Despa and his colleagues found that amylin accumulates in the blood vessels and muscle of the heart. From this evidence, he hypothesized that the same thing might be happening in the brain. To test the hypothesis he received a pilot research grant through the Alzheimer’s Disease Center.

The research was conducted using tissue from the brains of individuals over 65 donated to the UC Davis Alzheimer’s Disease Center: 15 patients with Alzheimer’s disease and type 2 diabetes; 14 Alzheimer’s disease patients without diabetes; and 13 healthy controls. A series of tests, including Western blot, immunohistochemistry and ELISA (enzyme-linked immunosorbent assay) were used to test amylin accumulation in specimens from the temporal cortex.

In contrast with the healthy brains, the brain tissue infiltrated with amylin showed increased interstitial spaces, cavities within the tissue, sponginess, and blood vessels bent around amylin accumulation sites.

Despa said that the finding may offer a therapeutic target for drug development, either by increasing the rate of amylin elimination through the kidneys, or by decreasing its rate of oligomerization and deposition in diabetic patients.

"If we’re smart about the treatment of pre-diabetes, a condition that promotes increased amylin secretion, we might be able to reduce the risk of complications, including Alzheimer’s and dementia,” Despa said.

(Source: ucdmc.ucdavis.edu)

Researchers in Spain have found that a drug used to control Type II diabetes can help repair the spinal cords of mice suffering from the inherited disease adrenoleukodystrophy which, untreated, leads eventually to a paralysis, a vegetative state and death. They believe that their findings may be relevant to other neurodegenerative diseases.  A Phase II trial will be starting shortly. The research is published simultaneously on line in the journal Brain.

A drug used to control Type II diabetes can help repair the spinal cords of mice suffering from the inherited disease adrenoleukodystrophy which, untreated, leads eventually to a paralysis, a vegetative state and death. This is an important step along the road to the development of a therapy for the human disease for which current treatment options are scarce and only partially effective, the annual conference of the European Society of Human Genetics will hear tomorrow (Sunday).

Professor Aurora Pujol, a research professor for the Catalan Government Research Body ICREA, working as Director of the Neurometabolic Diseases Laboratory at IDIBELL, Barcelona, Spain, investigated the role of mitochondria, the power plant of the cell, in adrenoleukodystrophy, a disease caused by the inactivation of the ABCD1 transporter of fatty acids in peroxisomes.  This inactivation leads to the accumulation of fatty acids in organs and blood plasma, and causes spinal cord degeneration.

“ABCD1 is a protein located in the peroxisomes, compartments of the cell that detoxify chemicals and lipids, and thus the implication of mitochondria in such a disease was not obvious.  But we knew from recent research that oxidative stress – where there is increased production of chemically active oxygen-containing molecules, and also significant decrease in the effectiveness of the body’s antioxidant defences – was involved.  We also knew that bioenergetic failure appeared before disease symptoms.  We therefore decided to investigate the role of the mitochondria”, Professor Pujol will say.

The group of diseases known as leukodystrophies are characterised by progressive loss of the myelin sheath, the fatty covering that acts as an insulator around nerve fibres.  Damage to the myelin sheath impairs the conduction of signals in the affected nerves and leads to locomotor problems. 

“We knew that early oxidative damage and bioenergetic dysfunction underlay the late onset degeneration of nerve fibres observed in the mouse model of X-linked adrenoleukodystrophy (X-ALD), the most frequently inherited leukodystrophy, so we looked at mitochondria for further clues.  We found that the X-ALD mice showed a loss of mitochondria at 12 months of age, prior to disease symptoms, so this could not be a consequence of the disease, but rather a contributing factor.  We also knew that the pathway involved in the mitochondrial loss could be treated by the use of the diabetes drug pioglitazone, so we decided to test its effect in the mice”, Professor Pujol will say.

Pioglitazone halted the nerve fibre degeneration by preventing the loss of mitochondria, and inhibiting metabolic failure and oxidative stress in the treated mice, and hence also halted locomotor disabilities.   The researchers were able to prove this both through analysis of spinal cords post mortem, and in vivo by putting the mice through a number of physical tests.

Although X-ALD is a relatively rare disease  with a minimum incidence of 1 in 17 000 males, there are other neurodegenerative disorders caused by myelin sheath degeneration, for example multiple sclerosis, and many others where impaired bioenergetics combined with oxidative stress and degeneration of axons are known to be involved.  The latter category of disease includes Parkinson’s, Huntington’s, and Alzheimer’s.  “It is possible that our findings may be relevant to these conditions as well,” says Professor Pujol.

“Following on from these promising results, together with Professor Patrick Aubourg from the Hôpital Bicêtre, Paris, we will shortly be starting a multi-centre phase II clinical trial of pioglitazone in adult patients suffering from a late onset variant of adrenoleukodystrophy.   Our research has shown that it will be feasible to monitor the biological effects of the drug by looking for biomarkers of oxidative damage in blood cells or plasma.  We are happy to have made a contribution to finding a simple and effective treatment to a group of devastating diseases”, she will conclude.

(Source: alphagalileo.org)