Insulin could be Alzheimer's therapy

April 1, 2011
Research by UB's Paresh Dandona shows that a low dose of insulin suppresses the expression of proteins involved in the pathogenesis of Alzheimer's disease. Credit: Doug Levere

A low dose of insulin has been found to suppress the expression in the blood of four precursor proteins involved in the pathogenesis of Alzheimer's disease, according to new clinical research by University at Buffalo endocrinologists. The research, published in March online in the Journal of Clinical Endocrinology and Metabolism, suggests that insulin could have a powerful, new role to play in fighting Alzheimer's disease.

"Our results show clearly that insulin has the potential to be developed as a therapeutic agent for Alzheimer's, for which no satisfactory treatment is currently available," says Paresh Dandona, MD, PhD, UB distinguished professor of medicine in the School of Medicine and Biomedical Sciences and senior author on the study.

One of the four proteins shown in the study to be suppressed by insulin is a precursor to beta amyloid, the main component of plaques considered the hallmark of Alzheimer's disease.

The findings also demonstrate for the first time that the four precursor proteins studied are expressed in peripheral mononuclear cells, that are an important component of the immune system.

The paper builds on the UB researchers' earlier work showing that insulin has a potent and rapid anti-inflammatory effect on peripheral mononuclear cells. It also builds on the well-known association between obesity, and chronic low-grade inflammation, as well as , all conditions that manifest a significantly increased prevalence of Alzheimer's disease.

In the study, 10 obese, type 2 diabetic patients were infused with two 100 ml units of insulin per hour over a period of four hours. The patients were all taking oral drugs to treat their diabetes; none of them were taking insulin or any antioxidant or nonsteroidal anti-inflammatory drugs. The control group received 5 percent dextrose per hour or normal saline solution.

The low-dose insulin was found to suppress the expression of amyloid precursor protein, from which beta amyloid is derived. It also suppressed presenilin-1 and presenilin-2, the two subunits of an enzyme that converts amyloid precursor protein into beta amyloid, which forms the amyloid plaques. Insulin also suppressed glycogen synthase kinase, which phosphorylates, or adds on another phosphate group, to another neuronal protein, tau, to form the neurofibrillary tangles, the other important component of Alzheimer's disease in the brain.

"Our data show, for the first time, that the peripheral mononuclear cells express some of the key proteins involved in the pathogenesis of Alzheimer's disease," says Dandona. "They demonstrate that these cells can be used for investigating the effect of potential Alzheimer's disease therapies on key proteins involved in the disease.

"Even more importantly, it is likely that insulin has a direct cellular effect on these precursor proteins while also exerting its other anti-inflammatory actions," he continues. "If this effect of insulin proves, in larger studies, to be systemic, then insulin may well be a potential therapeutic agent in treating Alzheimer's disease. The challenge is to deliver insulin directly into the brain, thus avoiding its hypoglycemic effect."
Fortunately, Dandona says, a previous preliminary study has shown that intranasal delivery of insulin can lead to its entry into the brain along the olfactory nerves and that its administration may improve cognitive function in patients with . However, he cautions, the mode of action is not known.

"Our study provides a potential rational mechanism," he says.

Related Stories

Recommended for you

Researchers discover key signaling protein for muscle growth

November 20, 2017
Researchers at the University of Louisville have discovered the importance of a well-known protein, myeloid differentiation primary response gene 88 (MyD88), in the development and regeneration of muscles. Ashok Kumar, Ph.D., ...

New breast cell types discovered by multidisciplinary research team

November 20, 2017
A joint effort by breast cancer researchers and bioinformaticians has provided new insights into the molecular changes that drive breast development.

Brain cell advance brings hope for Creutzfeldt-Jakob disease

November 20, 2017
Scientists have developed a new system to study Creutzfeldt-Jakob disease in the laboratory, paving the way for research to find treatments for the fatal brain disorder.

Hibernating ground squirrels provide clues to new stroke treatments

November 17, 2017
In the fight against brain damage caused by stroke, researchers have turned to an unlikely source of inspiration: hibernating ground squirrels.

Age and gut bacteria contribute to multiple sclerosis disease progression

November 17, 2017
Researchers at Rutgers Robert Wood Johnson Medical School published a study suggesting that gut bacteria at young age can contribute to multiple sclerosis (MS) disease onset and progression.

Molecular guardian defends cells, organs against excess cholesterol

November 16, 2017
A team of researchers at the Harvard T. H. Chan School of Public Health has illuminated a critical player in cholesterol metabolism that acts as a molecular guardian in cells to help maintain cholesterol levels within a safe, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.