How liver responds to food

Minutes after eating, as nutrients rush into the bloodstream the body makes massive shifts in how it breaks down and stores fats and sugars. Within half an hour, the liver has made a complete switch  from burning fat for energy to storing as much glucose, or sugar, as possible. It's too short a time span for the liver's cells to activate genes and produce the RNA blueprints needed to assemble new proteins to guide metabolism.

Liver cells store up pre-RNA molecules involved in glucose and fat metabolism. ''The switch from fasting to feeding is a very quick switch and human physiology has to adapt to it in the right time frame," says Satchidananda Panda, a professor in the Salk Institute's Regulatory Biology Laboratory. It was known that a RNA-binding protein called NONO was implicated in regulating daily ("circadian") rhythms in the body.

Researchers analyzed levels of NONO in response to feeding and fasting in mice. After the animals ate, speckled clumps of NONO suddenly appeared in their liver cells, newly attached to RNA molecules. Within half an hour, the levels of corresponding proteins-those encoded by the NONO-bound RNA increased.

After mice eat, it looks as if NONO brings all these RNAs together and processes them so they can be used to make proteins. When mice lacked NONO, it took more than three hours for levels of the same proteins involved in processing glucose to increase. During that time lag, blood glucose levels shot up to unhealthy levels.

Since blood glucose levels are also heightened in diabetes, the researchers think that the mice without NONO may act as a model to study some forms of the disease. NONO has been found at high levels in the brain and muscle cells.
          haleplushearty.blogspot.com

Gene therapy for type 1 diabetes

Type 1 diabetes is a chronic disease in which the immune system attacks and destroys insulin-producing beta cells in the pancreas, resulting in high blood levels of glucose. A gene therapy approach can lead to the long-term survival of functional beta cells as well as normal blood glucose levels for an extended period of time in mice with diabetes. The researchers used an adeno-associated viral (AAV) vector to deliver to the mouse pancreas two proteins, Pdx1 and MafA, which reprogrammed plentiful alpha cells into functional, insulin-producing beta cells.

A clinical trial in both type 1 and type 2 diabetics in the immediate foreseeable future is quite realistic, given the impressive nature of the reversal of the diabetes, along with the feasibility in patients to do AAV gene therapy. Approximately 9% of the world's adult population has diabetes, which can cause serious health problems such as heart disease, nerve damage, eye problems, and kidney disease.

One fundamental goal of diabetes treatment is to preserve and restore functional beta cells, thereby replenishing levels of a hormone called insulin, which moves blood glucose into cells to fuel their energy needs. But in patients with type 1 diabetes, beta-cell replacement therapy is likely doomed to failure because the new cells might fall victim to the same autoimmunity that destroyed the original cells.

A potential solution to this problem is to reprogram other cell types into functional beta-like cells, which can produce insulin but are distinct from beta cells and therefore are not recognized or attacked by the immune system. To explore the feasibility of this approach, Gittes and first author Xiangwei Xiao of the University of Pittsburgh School of Medicine engineered an AAV vector to deliver to the mouse pancreas proteins called Pdx1 and MafA, which support beta cell maturation, proliferation, and function.

The goal was to generate functional beta-like cells from pancreatic alpha cells, which may be the ideal source for beta cell replacement. For example, alpha cells are plentiful, resemble beta cells, and are in the correct location, all of which could facilitate reprogramming.

By comparing the gene expression patterns of normal beta cells and insulin-producing cells derived from alpha cells, the researchers confirmed nearly complete cellular reprogramming. This gene therapy approach restored normal blood glucose levels in diabetic mice for an extended period of time, typically around four months, and the new insulin-producing cells derived almost exclusively from alpha cells. Moreover, the strategy successfully generated functional insulin-producing cells from human alpha cells.

The viral gene therapy appears to create these new insulin-producing cells that are relatively resistant to an autoimmune attack. This resistance appears to be due to the fact that these new cells are slightly different from normal insulin cells, but not so different that they do not function well. Several features of this approach could facilitate translation to humans. For one, AAV vectors like those used in this study are currently undergoing various gene therapy trials in humans.

Moreover, the viral vectors can be delivered directly to the human pancreas through a routinely performed non-surgical endoscopic procedure; however, this procedure can elicit pancreatic inflammation. In addition, no immunosuppression is required, so patients would avoid related side effects such as an increased risk of infection. However, one major concern was that the mice did eventually return to the diabetic state, suggesting that this treatment would not represent a definitive cure for the disease.
          haleplushearty.blogspot.com

Link between obesity and diabetes

Researchers have identified a major mechanism by which obesity causes type 2 diabetes, which is a common complication of being overweight. In obesity, insulin released into the blood by the pancreas is unable to pass through the cells that form the inner lining of blood vessels.

As a result, insulin is not delivered to the muscles, where it usually stimulates most of the body's glucose to be metabolized. Blood glucose levels rise, leading to diabetes and its related cardiovascular, kidney and vision problems.

 A major problem in obesity is the delivery of circulating insulin to the muscle, this problem involves immunoglobulins, which are the proteins that make up circulating antibodies. The researchers found that obese mice have an unexpected chemical change in their immunoglobulins.

The abnormal immunoglobulins then act on cells lining blood vessels to inhibit an enzyme needed to transfer insulin from the bloodstream into the muscle. Type 2 diabetes patients have the same chemical change, and if immunoglobulins from a type 2 diabetic individual is given to a mouse, the mouse will becomes diabetic.
        haleplushearty.blogspot.com

How bones affect appetite and metabolism

Human skeleton is more than the structure supporting the muscles and other tissues, it produces osteocalcin hormone. The hormone affects how we metabolize sugar and fat. It increases insulin production which reduces blood glucose levels, it can also protects us from obesity by increasing the use of energy.

Changes in blood concentrations of osteocalcin may stave off the development of diabetes. Osteocalcin is produced by osteoblasts, the cells responsible for making human bones. The hormone builds up in bone, and then, through a series of chemical reactions, is released into the blood.

Inactive osteocalcin has one more piece than active osteocalcin. The researchers examined in mice the different enzymes present in cells where osteocalcin was produced. Furin causes osteocalcin to become active and the hormone is then released into the blood.

When there was no furin in bone cells, inactive osteocalcin built up and was still released, but this led to an increase in blood glucose levels and a reduction in energy expenditure and insulin production. The absence of furin reduced the mice's appetite, osteocalcin has no effect on appetite, the existence of a new bone hormone that controls food intake.
          haleplushearty.blogspot.com

Pancreatic islets and diabetes treatment

Researchers have discovered new insights into the molecular mechanisms of cell proliferation in juvenile human pancreatic islets, the discovery could lead to new treatments for diabetes. In type 1 and type 2 diabetes, the insulin-producing beta cells found in cell clusters in the pancreas, known as pancreatic islets, are either destroyed or become dysfunctional, leading to insulin deficiency.

Insulin is the hormone responsible for the regulation of blood glucose levels.
Researchers took viable samples of human pancreatic islet cells obtained from both juveniles, defined as age 10 or younger, and from adults, between the age of 20 to 60 years old. The islet cells were transferred into a mouse model lacking an immune system, which allowed the human cells to survive and function for several months.

These types of human islet cells had increased rates of proliferation after transfer into the mouse model, indicating this was an intrinsic property of the juvenile islet cells and not the pancreatic environment. Beta cell growth rate declines with age. Using a drug analogue of glucagon-like peptide 1 (GLP-1), a common clinical treatment for type 2 diabetes, it was shown over a period of four weeks that beta cell proliferation was stimulated only in the juvenile islet cells, but not in the adult cells.

In comparing the islet cells, it was discovered that the GLP-1 receptors were similar in both juvenile and adult pancreatic islets, suggesting that pathways inside the human juvenile islet cells were responsible for the different response in adult islet cells.
Researchers examined the series of interactions among the molecules of a cell that lead to a specific product or change in a cell. They discovered difference in the calcineurin pathway between the juvenile islet cells and the adult islets.
          haleplushearty.blogspot.com

Cocoa may delay Type 2 diabetes

Insulin is the hormone that manages glucose, the blood sugar that reaches unhealthy levels in diabetes patients is caused by insulin not working properly.

Failure of beta cells to produce insulin can leads to diabetes, the body of diabetes patients either doesn't produce enough insulin or doesn't process blood sugar properly.

Researchers have discovered certain compounds in cocoa that can aid the release of more insulin and respond to increased blood glucose. Beta cells work better and remain stronger with an increased presence of epicatechin monomers, compounds found in cocoa.

Researchers fed animals with the cocoa compound, they discovered that adding the compound to their diet decreases the level of obesity in the animals and increases their ability to regulate increased blood glucose levels.

This showed that cocoa compounds called epicatechin monomers enhanced beta cells' ability to secrete insulin by protecting the cells and increase their ability to deal with oxidative stress.

The epicatechin monomers are making the mitochondria in the beta cells stronger, which produces more ATP which leads to more production of insulin.
          haleplushearty.blogspot.com

Type 1 diabetes can be treated under the skin

Researchers have demonstrated that the space under our skin might be an optimal location to treat type 1 diabetes T1D. Transplanting of healthy pancreatic cells under the skin to produce insulin for blood glucose regulation.

Insulin-making beta cells, located in regions of the pancreas known as pancreatic islets, are damaged in type 1 diabetes patients, implanting healthy new cells could restore insulin function.

Pancreatic islets are scattered throughout the pancreas in between other pancreatic cells that secrete digestive enzymes. The space under the skin has a large area so that it can support many islets.

Researchers injected healthy pancreatic islets under the skin and found that normal blood sugar levels could be restored within three weeks.

Pancreatic islets comprise one per cent of the pancreas, but require twenty percent of the blood flow to the organ, adequate blood flow to the islets will make it work properly.
          haleplushearty.blogspot.com

Links between menopause and type 2 diabetes

The sex hormones- estrogen and progesterone control how cells respond to insulin. Hormonal changes during menopause can trigger fluctuations of insulin levels in the blood and leads to type 2 diabetes.

Estrogen hormone lowers blood glucose levels while progesterone is responsible for increasing blood glucose levels. This hormonal reactions produce spikes and drops of the blood glucose levels.

According to the latest research, women who undergo the menopause before age 40 are at greater risk of developing type 2 diabetes. Menopause occurs between age 50 - 55  when the body stops producing oestrogen and other sex hormones.

Researchers examined many postmenopausal women and discovered that those that experienced early menopause have type 2 diabetes. Late menopause protects women from heart disease and diabetes because of regular natural supply of estrogen.
          haleplushearty.blogspot.com

Broccoli can cure type 2 diabetes

Eating or drinking broccoli can reverse type 2 diabetes. Sulforaphane is an anti-cancer compound in cruciferous vegetables.

Sulforaphane is highly concentrated in cruciferous vegetables and could be used in a concentrated broccoli extract.
It can be used for treatment of type 2 diabetes.

Researchers examined  97 obese patients, those given concentrated broccoli sprout found their fasting blood glucose levels fell dramatically compared to controls who received a placebo.

Sulforaphane induces an antioxidant response. It reduced glucose production by liver cells growing in culture, and shifted liver gene expression in diabetic rats.


         haleplushearty.blogspot.com

Benefits of calories reduction

When the body does not have enough glucose for energy, it burns stored fats, resulting in a build-up of molecules called ketone bodies.

Investigators suspect that calorie reduction extends life span at least in part through increasing levels of ketone bodies.

Aging-induced change like incidence of malignancies in mice, the increases in blood glucose and insulin caused by insulin resistance, and muscular weakness.

Insulin resistance can be decreased by the metabolism of ketone bodies, a normal metabolite produced from fatty acids by liver during periods of prolonged fasting or caloric reduction.

The more calorie you reduce, the less fat your body will accumulate. Less accumulation of fat in the body makes you healthy, it prevents diabetes and other terminal diseases.