Insulin could be Alzheimer's therapy

Apr 01, 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.

Explore further: Education, breastfeeding and gender affect the microbes on our bodies

add to favorites email to friend print save as pdf

Related Stories

Insulin is a possible new treatment for Alzheimer's

Feb 02, 2009

A Northwestern University-led research team reports that insulin, by shielding memory-forming synapses from harm, may slow or prevent the damage and memory loss caused by toxic proteins in Alzheimer's disease.

Anti-inflammatory drug blocks brain plaques

Jun 24, 2008

Brain destruction in Alzheimer's disease is caused by the build-up of a protein called amyloid beta in the brain, which triggers damaging inflammation and the destruction of nerve cells. Scientists had previously shown that ...

Scientists find new cause of Alzheimer's

Apr 19, 2006

Belgium researchers say they are the first to demonstrate the quantity of amyloid protein in brain cells is a major factor of Alzheimer's disease.

Researchers find new piece in Alzheimer's puzzle

Feb 25, 2009

Yale researchers have filled in a missing gap on the molecular road map of Alzheimer's disease. In the Feb. 26 issue of the journal Nature, the Yale team reports that cellular prion proteins trigger the process by which ...

Recommended for you

Leeches help save woman's ear after pit bull mauling

8 hours ago

(HealthDay)—A pit bull attack in July 2013 left a 19-year-old woman with her left ear ripped from her head, leaving an open wound. After preserving the ear, the surgical team started with a reconnection ...

New pain relief targets discovered

19 hours ago

Scientists have identified new pain relief targets that could be used to provide relief from chemotherapy-induced pain. BBSRC-funded researchers at King's College London made the discovery when researching ...

Building 'smart' cell-based therapies

20 hours ago

A Northwestern University synthetic biology team has created a new technology for modifying human cells to create programmable therapeutics that could travel the body and selectively target cancer and other ...

User comments : 0

More news stories

Vietnam battles fatal measles outbreak

Vietnam is scrambling to contain a deadly outbreak of measles that has killed more than 100 people, mostly young children, and infected thousands more this year, the government said Friday.

Continents may be a key feature of Super-Earths

Huge Earth-like planets that have both continents and oceans may be better at harboring extraterrestrial life than those that are water-only worlds. A new study gives hope for the possibility that many super-Earth ...

Researchers successfully clone adult human stem cells

(Phys.org) —An international team of researchers, led by Robert Lanza, of Advanced Cell Technology, has announced that they have performed the first successful cloning of adult human skin cells into stem ...