Insulin Therapy May Help Repair Atherosclerotic Lesions in Diabetic Patients

New research reveals that insulin applied in therapeutic doses selectively stimulates the formation of new elastic fibers in cultures of human aortic smooth muscle cells. These results advance the understanding of the molecular and cellular mechanisms of diabetic vascular disease. The study is published in the February issue of the American Journal of Pathology.

“Our results particularly endorse the use of insulin therapy for the treatment of atherosclerotic lesions in patients with type I diabetes, in which the induction of new elastic fibers would mechanically stabilize the developing plaques and prevent arterial occlusions,” explained lead investigator Aleksander Hinek, MD, PhD, DSc, Professor, Division of Cardiovascular Research, The Hospital for Sick Children and the Department of Laboratory Medicine and Pathobiology, University of Toronto.

Primary insulin deficiency and decreased cellular sensitivity to insulin have been implicated in the pathogenesis of impaired healing processes, atherosclerosis and hypertension, all frequently observed in patients with both type I and type II diabetes.

However, the possibility of a direct contribution of insulin to the cellular and molecular mechanisms that control the production of elastic fibers (elastogenesis) has not been explored. The researchers conducted a series of experiments to determine whether low therapeutic concentrations of insulin would promote the production of elastic fibers in cultures of human aortic smooth muscle cells.

Investigators found that insulin does in fact stimulate the deposition of elastic fibers in cultures of human aortic smooth muscle cells. The data demonstrated, for the first time, that low doses of insulin induce the elastogenic effect solely through the activation of insulin receptor and trigger the downstream activation of the P13K signaling pathway. The ultimate up-regulation of elastic fiber deposition by insulin is executed through two parallel mechanisms: the initiation of elastin gene expression and the enhancement of tropoelastin secretion.

Importantly, the experimental data suggest that insulin-dependent initiation of the elastin gene transcription occurs after dissociation of the FoxO1 transcription factor from the specific domain identified within the elastin gene promoter. The researchers also demonstrated that insulin may facilitate the transportation of tropoelastin into the secretory endosomes, where it can associate with S-GAL/EBP, the “chaperone” protein that enhances secretion.

“We believe that our discovery of the elastogenic action of insulin allows for better understanding of the pathologic mechanisms in which the lack of insulin, in diabetes type I, or insulin resistance, in diabetes type II, contribute to the development of hypertension and the rapid progression of atherosclerosis,” concluded Dr. Hinek.

Dr. Hinek further elaborated on the far-reaching effects these data provide: “Importantly, our newest results indicate that the discovered elastogenic effect of low concentrations (0.5-10 nM) of insulin is not restricted to the arterial smooth muscle cells. Thus, insulin also stimulates formation of elastic fibers by human skin fibroblasts and by myofibroblasts isolated from human hearts.

These observations constitute a real novelty in the field of regenerative medicine and endorse 1) local application of small doses of insulin for ameliorating difficult healing of dermal wounds in diabetic patients and 2) systemic administration of insulin in patients after heart infarctions, in hope that insulin-induced elastic fiber deposition may alleviate formation of maladaptive collagenous scars in the myocardium.”

The article is “Insulin Induces Production of New Elastin in Cultures of Human Aortic Smooth Muscle Cells,” by J. Shi, A. Wang, S. Sen, Y. Wang, J. Kim, T.J. Mitts, and A. Hinek (DOI: 10.1016/j.ajpath.2011.10.022). It will appear in The American Journal of Pathology, Volume 180, Issue 2 (February 2012) published by Elsevier.

Decaffeinated Coffee Preserves Memory Function by Improving Brain Energy Metabolism

Researchers from Mount Sinai School of Medicine have discovered that decaffeinated coffee may improve brain energy metabolism associated with type 2 diabetes. This brain dysfunction is a known risk factor for dementia and other neurodegenerative disorders like Alzheimer’s disease. The research is published online in Nutritional Neuroscience.

A research group led by Giulio Maria Pasinetti, MD, PhD, Professor of Neurology, and Psychiatry, at Mount Sinai School of Medicine, explored whether dietary supplementation with a standardized decaffeinated coffee preparation prior to diabetes onset might improve insulin resistance and glucose utilization in mice with diet-induced type 2 diabetes.

The researchers administered the supplement for five months, and evaluated the brain’s genetic response in the mice. They found that the brain was able to more effectively metabolize glucose and use it for cellular energy in the brain. Glucose utilization in the brain is reduced in people with type 2 diabetes, which can often result in neurocognitive problems.

“Impaired energy metabolism in the brain is known to be tightly correlated with cognitive decline during aging and in subjects at high risk for developing neurodegenerative disorders,” said Dr. Pasinetti. “This is the first evidence showing the potential benefits of decaffeinated coffee preparations for both preventing and treating cognitive decline caused by type 2 diabetes, aging, and/or neurodegenerative disorders.”

Coffee intake is not recommended for everybody due to the fact that it is associated with cardiovascular health risks such as elevated blood cholesterol and blood pressure, both of which lead to an increased risk for heart disease, stroke, and premature death. These negative effects have primarily been attributed to the high caffeine content of coffee. Nonetheless, these novel findings are evidence that some of the non-caffeine components in coffee provide health benefits in mice. Dr. Pasinetti hopes to explore the preventive role of decaffeinated coffee delivered as a dietary supplement in humans.

“In light of recent evidence suggesting that cognitive impairment associated with Alzheimer’s disease and other age-related neurodegenerative disorders may be traced back to neuropathological conditions initiated several decades before disease onset, developing preventive treatments for such disorders is critical,” he said.

Insulin Resistance Linked to Brain Health

New research from Uppsala University shows that reduced insulin sensitivity is linked to smaller brain size and deteriorated language skills in seniors. The findings are now published in the scientific journal Diabetes Care.

The main hormonal function of insulin is to support the uptake and use of glucose in muscles and fat tissues. However, in an earlier article recently published in Molecular Neurobiology, Christian Benedict from the Department of Neuroscience at Uppsala University has reported that when insulin reaches the brain, it enhances memory function in humans. As insulin’s capacity to stimulate glucose metabolism generally declines with age, it may also be that it affects the rate of cognitive aging in seniors.

In a new study, Christian Benedict, together with colleagues from Uppsala University (Samantha Brooks, Håkan Ahlström, Lars Lind, and Helgi Schiöth), the UK, and the US, have systematically studied 331 men and women at the age of 75 years. The researchers examined whether insulin sensitivity is tied to brain health. The brain structure of each participant was measured using magnetic imaging technology, so-called MRT, and their language skills were tested by asking them to name as many animals as possible in one minute (so-called verbal fluency).

“We found that in elderly whose insulin sensitivity was still high, the brains were larger, and they had more grey matter in regions that are important for language skills, compared with those who had diminished insulin sensitivity. We also observed that higher insulin sensitivity was associated with better scores on the language test. Our findings offer a possible explanation for why methods that improve insulin sensitivity, such as exercise, are promising strategies for counteracting cognitive aging late in life,” says Christian Benedict.

The data for the study were taken from the major epidemiological study Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS).

Benedict C et al. Impaired insulin sensitivity as indexed by the HOMA score is associated with deficits in verbal fluency and temporal lobe gray matter volume in elderly. Diabetes Care, in press.

Bold new avenue for type 1 diabetes research

Researchers from the University of Pittsburgh have discovered new ways to grow human beta cells in the laboratory. The researchers were able to induce the cells to divide and, notably, to stop the cells from dividing as well.
The cell division was achieved by adding the genes ‘cdk’ and ‘cyclin d’ into the beta cells. The way the genes were introduced into the beta cells was via a virus which was able to penetrate into the cells and deliver the genes.
Beta cells are usually very slow to divide within the body which is one reason why type 1 diabetes is able to develop very quickly. Type 1 diabetes begins when the body’s immune system attacks its own insulin producing beta cells. Within a period of weeks, someone with type 1 diabeteswill have lost sufficient beta cells to require insulin injections to keep blood sugar levels even.
Previously, beta cells have only been available from human or animal donors. This has meant that beta cells have been in short supply even for research purposes. Production of beta cells from the new method described could open doors for more research into beta cells to be possible. The research led by Professor Andrew Stewart was funded by the JDRF.

Elevated Glucose Associated With Undetected Heart Damage

A new study led by researchers at the Johns Hopkins Bloomberg School of Public Health suggests that hyperglycemia (high blood sugar) injures the heart, even in patients without a history of heart disease or diabetes. Researchers found that elevated levels of glycated hemoglobin (HbA1c), a marker for chronic hyperglycemia and diabetes, were associated with minute levels of the protein troponin T (cTnT), a blood marker for heart damage. The high-sensitivity test they used detected levels of cTnT tenfold lower than those found in patients diagnosed with a heart attack.

The findings, which are published in the latest issue of the Journal of the American College of Cardiology, suggest that hyperglycemia may be related to cardiac damage independent of atherosclerosis.

“Hyperglycemia and diabetes are known to be associated with an increased risk for heart attack and coronary disease and our study sheds some light on what may be happening,” said Elizabeth Selvin, PhD, MPH, senior author of the study and associate professor in the Bloomberg School’s Department of Epidemiology. “Our results suggest that chronically elevated glucose levels may contribute to heart damage.”

For the study, the researchers followed 9,662 participants from the Atherosclerosis Risk in Communities (ARIC) study. None of the participants had coronary heart disease or history of heart failure. Higher levels of HbA1c were associated in a graded fashion with elevated levels of high-sensitivity cTnT. This relationship was present at HbA1c levels even below the threshold used to diagnose diabetes. Using conventional tests, troponin T can be detected in 0.7 percent of the population and is associated with heart attacks and death. With the high-sensitivity cTnT test, low levels of troponin were found in 66 percent of the study population.

“Our study hints at other potential pathways by which diabetes and elevated glucose are associated with heart disease. Mainly, glucose might not only be related to increased atherosclerosis, but potentially elevated glucose levels may directly damage cardiac muscle,” said Jonathan Rubin, MD, general internal medicine fellow at the Johns Hopkins School of Medicine. He was lead author of the study while studying at the Johns Hopkins Bloomberg School of Public Health.

Additional authors of “Chronic Hyperglycemia and Subclinical Myocardial Injury” include Kunihiro Matsushita, MD, PhD, and Josef Coresh, MD, PhD, of the Bloomberg School of Public Health; and Christine M. Ballantyne, MD, and Ron Hoogeveen, PhD, of the Baylor College of Medicine.

The research was supported with grants from the National Heart, Lung, and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health.

Lyrics of Depression–Newest Hello Cupcake Its Me Song.

I had been feeling shitty for a while and just got it all down on paper one night and decided to turn it into a song, and I found my man Zachary Baekelandt and he made my dream a reality. As you probably remember I had another song made for me called Lives are on the Line,  which was more of a Country/Blues feel. I am hoping to get enough music together to release an album, that has songs that are ranging in all topics. So I have Diabetes, and Depression, now I just need to think of some more.

Please tell me what you think about this song. I look forward to your comments

Enraged by the Henderson Nevada Police

Ok so I just got done watching this Youtube clip from 8 News Now in Henderson Nevada of 6 Police Officers beating a man who was in Diabetic Shock. They can be seen kicking and hitting him. All because he didn’t pull over in time. See this is what is wrong with the American Police Force. They automatically resort to violence rather than to talk things out or even get the just of what is going on in the situation. You can clearly see that the guy is not responsive, and makes no threating movements. I understand that being a Cop is a hard job and that they are putting their lives on the line daily, but really is force necessary when it comes to all situations.

What are your thoughts on this?

http://www.8newsnow.com/story/16770611/breaking-news-henderson-officer-in-beating-video-identified

Sister Moving

Thanks to Olga Quinn

My sister recently relocated to Texas. She has had such a hard time lately. She is going through her second divorce. Neither of them have been by her doing. Her first husband cheated on her and then left her. Her most recent husband lost his job and turned to drugs and alcohol instead of his family. It was really sad to see him deteriorate, but I am so proud of my sister for leaving him. She is doing what she needs to do to protect her children. I think a new start in Texas may be just the thing for her. It won’t be easy though. Money is going to be very tight. Her last husband isn’t paying any support because he doesn’t have a job. I tried to offer her money, but of course she would not accept it. I think I just need to buy her something rather than give her money. I went to harlingentxsatellitetv.com and payed for her service. I hope she isn’t mad when I tell her. I know deep down it will be a relief for her.

Diabetes quadruples birth defects risk, say researchers

The risk of birth defects increases four-fold if the pregnant mother has diabetes, researchers say.

The Newcastle University study, published in the journal Diabetologia, analyzed data from more than 400,000 pregnancies in North East England.

The risk of defects such as congenital heart disease and spinal bifida were increased.

National guidelines already recommend having good control over blood sugar levels before trying to conceive.

Both Type 1 diabetes, which tends to appear in childhood, and Type 2 diabetes, often linked to diet, lead to problems controlling the amount of sugar in the blood.

This is known to cause problems in pregnancy, such as birth defects, miscarriage and the baby being overweight due to too much sugar.

There is concern that rising levels of diabetes, particularly Type 2, could make the issue worse.

Researchers analyzed data from 401,149 pregnancies between 1996 and 2008 – 1,677 women had diabetes.

The risk of birth defects went from 19 in every 1,000 births for women without pre-existing diabetes to 72 in every 1,000 births for women with diabetes.

Their report said that sugar levels in the run-up to conception were the “most important” risk factor which could be controlled.

The lead researcher, Dr Ruth Bell from Newcastle University, told the BBC: “Many of these anomalies happen in the first four to six weeks.”

She said the number of pregnancies with poor sugar control were “more than we would like”.

“It is a problem when the pregnancy is not intended or when people are not aware they need to talk to their doctors before pregnancy,” she said.

Guidelines from the National Institute of Health and Clinical Excellence say women should reduce their levels of glycated haemoglobin (HbA1c – a marker for long-term blood sugar control) to below 6.1% before trying to have a baby.

Dr Bell said: “The good news is that, with expert help before and during pregnancy, most women with diabetes will have a healthy baby.

“The risk of problems can be reduced by taking extra care to have the best possible glucose control before becoming pregnant.”

The charity Diabetes UK funded the study. Its director of research, Dr Iain Frame, said: “We need to get the message out to women with diabetes that if they are considering becoming pregnant, then they should tell their diabetes healthcare team, who will make sure they are aware of planning and what next steps they should be taking.

“It also highlights the importance of using contraception if you are a woman with diabetes who is sexually active but not planning to become pregnant.”

Source: By James GallagherHealth and science reporter, BBC News

Researchers Isolate Protein Linking Exercise to Health Benefits

A team led by researchers at Dana-Farber Cancer Institute has isolated a natural hormone from muscle cells that triggers some of the key health benefits of exercise. They say the protein, which serves as a chemical messenger, is a highly promising candidate for development as a novel treatment for diabetes, obesity and perhaps other disorders, including cancer.

Bruce Spiegelman, PhD, a cell biologist at Dana-Farber, is senior author of the report, posted as an advanced online publication by the journal Nature. The first author is Pontus Bostroöm, MD, PhD, a postdoctoral fellow in the Spiegelman lab.

“It’s exciting to find a natural substance connected to exercise that has such clear therapeutic potential,” said Bostroöm.

Spiegelman dubbed the hormone “irisin,” after Iris, a Greek messenger goddess. He said the discovery is an important first step in understanding the biological mechanisms that translate physical exercise into beneficial changes throughout the body, both in healthy people and in preventing or treating disease.

“There has been a feeling in the field that exercise ‘talks to’ various tissues in the body,” said Spiegelman, a professor of cell biology at Harvard Medical School. “But the question has been, how?”

According to the report, the irisin hormone has direct and “powerful effects” on adipose, or fatty, tissue — subcutaneous deposits of white fat that store excess calories and which contribute to obesity.

When irisin levels rise through exercise — or, in this study, when irisin was injected into mice — the hormone switches on genes that convert white fat into “good” brown fat. This is beneficial because brown fat burns off more excess calories than does exercise alone.

Only a small amount of brown fat is found in adults, but infants have more — an evolutionary echo of how mammals keep themselves warm while hibernating. In the wake of findings by Spiegelman and others, there has been a surge of interest in the therapeutic possibilities of increasing brown fat in adults.

Along with stimulating brown fat development, irisin was shown to improve glucose tolerance, a key measure of metabolic health, in mice fed a high-fat diet.

The discovery won’t allow people will be able to skip the gym and build muscles by taking irisin supplements, Spiegelman cautioned, because the hormone doesn’t appear to make muscles stronger. Experiments showed that irisin levels increase as a result of repeated bouts of prolonged exercise, but not during short-term muscle activity.

The Dana-Farber team identified irisin in a search for genes and proteins regulated by a master metabolic regulator, called PGC1-alpha, that is turned on by exercise. Spiegelman’s group had discovered PGC1-alpha in previous research.

Bostroöm said the hunt for molecular targets of increased PGC1-alpha activity ultimately pinpointed irisin, which turned out to be located within the outer membrane of muscle cells. This discovery ran counter to other scientists’ contentions that such a protein would reside in the cell’s nucleus.

To test whether increasing irisin alone could mimic exercise benefits, the scientists injected modest amounts into sedentary mice that were obese and pre-diabetic.

With 10 days of treatment, the mice had better control of blood sugar and insulin levels — in effect, preventing the onset of diabetes — and lost a small amount of weight. Although the weight loss was small, Spiegelman said that the hormone may have a greater effect when given for longer periods.

There were no signs of toxicity or side effects, which was predicted since the researchers limited the increase of irisin to levels typically caused by exercise.

In part because it is a natural substance and because the mouse and human forms of the protein are identical, Spiegelman said it should be possible to move an irisin-based drug rapidly into clinical testing — perhaps within two years.

The irisin discovery has been licensed by Dana-Farber exclusively to Ember Therapeutics for drug development. Ember is a Boston-based startup co-founded by Spiegelman and scientists at the Joslin Diabetes Center and the Scripps Research Institute in Florida.

The scientists said their findings merely scratch the surface of irisin’s multiple effects. They are continuing to explore the hormone’s possible benefits in metabolic diseases like diabetes, insulin resistance, and obesity, which constitute a growing epidemic around the world, as well as neurodegenerative illnesses like Parkinson’s disease.

Spiegelman added that as growing evidence implicates obesity and physical inactivity in cancer development, it’s conceivable irisin-based drugs may have value in prevention and treatment of the disease.