insulin resistance

Posted on Diabetes

Researchers question the role insulin resistance plays in diabetes

Insulin can be stored out of refrigeration in hot settings
Insulin



What if current treatment of insulin resistance was only perpetuating the disease and causing disease to get worse?  According to Boston University School of Medicine (BUSM) researchers type 2 diabetes patients are often prescribed drugs that increase insulin release into the blood, which lowers blood glucose but may in fact increase the insulin resistance with long-term use. Many of these patients have elevated insulin even when glucose is normal.

Insulin is the hormone that allows tissues like muscle and fat to take up glucose from the blood to be used as fuel for energy needs. It is released from the pancreas into the blood stream when blood glucose levels increase, such as after a meal. Thus, insulin is secreted to lower blood glucose and keep it at a normal healthy level.

When nutrients such as fatty acid circulate through the blood at a constant high level it can damage tissue function. Insulin resistance is an impairment that occurs in muscle and fat making it harder for insulin to allow these tissues to take up glucose and lower blood glucose to a normal level. As a result, insulin increases to a level that is above normal and remains elevated even between meals and overnight. This causes the pancreas to maintain greater than normal blood insulin levels, a condition known as hyperinsulinemia and that precedes and can result in type 2 diabetes (T2D).

The medical field has long believed that insulin resistance is the root cause of this elevated blood insulin. However, a new review article highlights an opposing view that hyperinsulinemia is initially driven by insulin hypersecretion from beta cells impaired by the excess nutrients and environmental toxins. “Thus increased insulin release from the pancreas drives blood insulin levels higher causing/contributing to insulin resistance,” explains corresponding author Barbara E. Corkey, PhD, professor emeritus of medicine at BUSM.

According to the researchers, T2D patients often are prescribed drugs that increase insulin release into the blood, which lowers blood glucose but may in fact increase the insulin resistance with long-term use. “Our article describes a testable model in which chronic excess nutrient exposure results in insulin hypersecretion from the beta cell contributing to hyperinsulinemia. Hyperinsulinemia normally precedes measurable insulin resistance and T2D. It is viewed by many as a normal response to insulin resistance rather than its potential cause,” says Corkey.  

The researchers hope this review will highlight the potential damaging effects of increasing insulin release into the blood when levels are already elevated above normal levels due to insulin resistance. “Rather new therapeutic solutions that include lowering insulin levels before T2D develops may be warranted to prevent insulin resistance further developing into T2D,” said Corkey. 

Posted on Diabetes

Blocking a protein in liver cells protects against insulin resistance, fatty liver disease

Mitochondria inside liver cells (hepatocytes). CREDIT Mayuko Segawa, Liesa lab at UCLA Health

A new multi-institution study led by a team of researchers at the David Geffen School of Medicine demonstrated that blocking a protein called ABCB10 in liver cells protects against high blood sugar and fatty liver disease in obese mice. Furthermore, ABCB10 activity prompted insulin resistance in human liver cells.

The findings are the first to show that ABCB10 transports biliverdin out of the mitochondria – the cell’s “energy generating powerhouses.” Biliverdin is the precursor of bilirubin, a substance with antioxidant properties. Consequently, ABCB10 transport activity causes an increase in bilirubin synthesis inside liver cells undergoing fatty liver disease.

BACKGROUND

Non-alcoholic fatty liver disease is closely linked to obesity and other disorders related to insulin resistance and is becoming increasingly common throughout the world, affecting an estimated 100 million people in the United States.

The liver filters everything that people consume and sorts it for the nutrients that will stay in the body or for the toxins that it will expel. The liver is also one of the organs richest in mitochondria – the small organelles in cells that convert food into usable energy through a process called metabolism. Consequently, the mitochondria produce high levels of free radicals, as well as antioxidants to keep these free radicals at healthy levels. Both free radicals and antioxidants play a key role in regulating metabolism and are elevated in insulin resistance and fatty liver disease.

One of these antioxidants is bilirubin, a yellow-bile substance that is released from the breakdown of biliverdin – its green-bile precursor. Bilirubin is produced at high levels in livers from people with fatty liver disease. Both biliverdin and bilirubin are found naturally in the body and released during the breakdown of heme – the deep red iron-containing molecule in red blood cells, which can be seen in the changing color of bruises – from green (biliverdin) to yellow (bilirubin).

Previous research established that mild increases in blood bilirubin content could be associated with protection from metabolic diseases. However, the effects of bilirubin content inside mitochondria and their relationship to fatty liver disease and insulin resistance, remained unknown. This current study shows that increased bilirubin content inside the mitochondria driven by ABCB10 activity is contributing to fatty liver disease.

METHODS

In the study, the researchers removed the ABCB10 protein selectively from the livers of mice to test whether ABCB10 removal impacted the ability of obese mice to tolerate glucose, if they developed fat in the liver and how well the mitochondria in their livers were working to convert nutrients into usable energy.

In lean mice, the researchers found no difference in metabolism and health when ABCB10 was removed from their livers, while in obese mice they found that removing ABCB10 protected against insulin resistance and fatty liver disease.

Secondly, the researchers measured bilirubin in the mitochondria of liver cells using fluorescent sensors, as well as testing purified ABCB10 to determine what ABCB10 transports. They found that ABCB10 transports biliverdin out of the mitochondria and increases bilirubin production in liver cells, with ABCB10 removal decreasing mitochondrial bilirubin content to levels observed in lean mice.

Thirdly, the researchers found that when they restored bilirubin content in the mitochondria, the benefits on the function of mitochondria resulting from the removal of ABCB10 were reversed.

IMPACT

These findings shed light on the relevance of the association of some genetic ABCB10 variants with insulin resistance in Type 2 diabetes. While still very early to draw any conclusions, these findings could inspire the development of therapies that target ABCB10 or mitochondrial bilirubin in the liver to reverse fatty liver disease in obese individuals.

Posted on Fibromyalgia

Does insulin resistance cause fibromyalgia?

Insulin Signaling and Autism

Researchers led by a team from The University of Texas Medical Branch at Galveston were able to dramatically reduce the pain of fibromyalgia patients with medication that targeted insulin resistance.

This discovery could dramatically alter the way that chronic pain can be identified and managed. Dr. Miguel Pappolla, UTMB professor of neurology, said that although the discovery is very preliminary, it may lead to a revolutionary shift on how fibromyalgia and related forms of chronic pain are treated. The new approach has the potential to save billions of dollars to the health care system and decrease many peoples’ dependence on opiates for pain management.

The UTMB team of researchers, along with collaborators from across the U.S., including the National Institutes of Health, were able for the first time, to separate patients with fibromyalgia from normal individuals using a common blood test for insulin resistance, or pre-diabetes. They then treated the fibromyalgia patients with a medication targeting insulin resistance, which dramatically reduced their pain levels. The study was recently published in PlosOne.

Fibromyalgia is one of the most common conditions causing chronic pain and disability. The global economic impact of fibromyalgia is enormous – in the U.S. alone and related health care costs are about $100 billion each year. Despite extensive research the cause of fibromyalgia is unknown, so there’s no specific diagnostics or therapies for this condition other than pain-reducing drugs.

“Earlier studies discovered that insulin resistance causes dysfunction within the brain’s small blood vessels. Since this issue is also present in fibromyalgia, we investigated whether insulin resistance is the missing link in this disorder,” Pappolla said. “We showed that most – if not all – patients with fibromyalgia can be identified by their A1c levels, which reflects average blood sugar levels over the past two to three months.”

Pre-diabetics with slightly elevated A1c values carry a higher risk of developing central (brain) pain, a hallmark of fibromyalgia and other chronic pain disorders.”

The researchers identified patients who were referred to a subspecialty pain medicine clinic to be treated for widespread muscular/connective tissue pain. All patients who met the criteria for fibromyalgia were separated into smaller groups by age. When compared with age-matched controls, the A1c levels of the fibromyalgia patients were significantly higher.

“Considering the extensive research on fibromyalgia, we were puzzled that prior studies had overlooked this simple connection,” said Pappolla. “The main reason for this oversight is that about half of fibromyalgia patients have A1c values currently considered within the normal range. However, this is the first study to analyze these levels normalized for the person’s age, as optimal A1c levels do vary throughout life. Adjustment for the patients’ age was critical in highlighting the differences between patients and control subjects.”

For the fibromyalgia patients, metformin, a drug developed to combat insulin resistance was added to their current medications. They showed dramatic reductions in their pain levels.

Leave a comment Posted on A to Z of Medical Conditions, Skin conditions

Acanthosis nigricans – what are the signs and why we need to be aware of it?




Acanthosis nigricans

Acanthosis nigricans

It’s not a condition in itself, but can be a sign of an underlying health problem. These underlying conditions aren’t usually serious, although occasionally acanthosis nigricans can be sign of cancer.

Signs and symptoms




Dark, velvety patches.  If you have acanthosis nigricans, you’ll have thickened, brownish-grey or black patches of skin.

The patches will be dry and rough, feeling similar to velvet. They may also be itchy.

These patches may occur anywhere, but are usually seen around the neck, in the armpit, around the groin and sometimes in other skin folds. Occasionally, the skin over the joints of the fingers and toes may be affected, as well as the lips, palms of the hands and soles of the feet.

The patches usually develop slowly over time. Patches that grow and spread quickly are more likely to be associated with cancer. In these cases, the mouth, tongue, throat, nose and windpipe may also be affected.

Tiny growths on the skin

You may also have lots of tiny finger-like growths from the patches. This is known as papillomatosis.

There may also be skin tags around the affected area. These are small flesh-coloured or pigmented growths that hang off the skin and look a bit like warts.

When to see your GP

Acanthosis nigricans is usually harmless, but as it can be a sign of something serious it’s a good idea to see your GP if you think you have it. They may suspect acanthosis nigricans just by looking at your skin.

If the cause isn’t clear, you may have blood tests to check your blood sugar or hormone levels, and you might need additional tests such as an endoscopy or X-ray.

What causes acanthosis nigricans?

Acanthosis nigricans sometimes occurs in people who are otherwise in good health, particularly dark-skinned people of African descent.

However, in most cases it’s a sign of an underlying problem or condition such as obesity, diabetes or abnormal hormone levels. Some of the main causes of acanthosis nigricans are outlined below.

Obesity

Acanthosis nigricans is usually the result of obesity. This is known as obesity-associated acanthosis nigricans.




It occurs because obesity can cause insulin resistance (when the body is unable to properly use the hormone insulin), which may lead to high levels of insulin in the blood, affecting the skin cells.

Insulin resistance can also cause type 2 diabetes, so acanthosis nigricans can be an early sign that you have diabetes or are at risk of developing the condition.

Syndromes and hormone problems

Acanthosis nigricans is sometimes associated with an underlying syndrome or hormone problem, such as:

This type of acanthosis nigricans is known as syndromic acanthosis nigricans.

Genes

In rare cases, acanthosis nigricans can be caused by a faulty gene inherited directly from your parents. This is known as familial or benign genetic acanthosis nigricans.

This type is usually passed on in an autosomal dominant pattern, which means it can be passed on if only one of your parents carries the faulty gene.

Cancer

If the dark skin patches come on suddenly and spread quickly, it may be a sign you have cancer (usually stomach cancer). This is known as malignant acanthosis nigricans.

This is a rare condition that tends to affect middle-aged or elderly people, regardless of their weight or ethnic background.

The patches are more severe and the mouth, tongue and lips may also be affected. The skin may also become irritated and itchy.

How acanthosis nigricans is treated

Treatment for acanthosis nigricans aims to correct the underlying cause of your symptoms. This will usually cure the acanthosis nigricans or significantly improve the appearance of your skin.

Treatments that may be recommended include:

There’s no specific treatment to get rid of the patches, but a dermatologist (skin specialist) may be able to recommend treatments such as creams or tablets that may help improve the look of your skin.

Outlook

Most cases of acanthosis nigricans are harmless and not a sign of anything serious. The skin patches often fade with time as the underlying condition is treated.

If you have inherited acanthosis nigricans from your parents, your patches may gradually get bigger before staying the same or eventually fading on their own.

Only in cases where there is underlying cancer is the situation very serious. If the tumour is successfully treated, the condition may disappear, but unfortunately the types of cancer that cause acanthosis nigricans tend to spread quickly and a cure is often not possible.

[Original article on NHS Choices website]