Breakthrough research of essential molecule reveals important targets in diabetes and obesity

Insulin is the most potent physiological anabolic agent for tissue-building and energy storage, promoting the storage and synthesis of lipids, protein and carbohydrates, and inhibiting their breakdown and release into the circulatory system. It also plays a major role in stimulating glucose entry into muscle tissue, where the glucose is metabolized and removed from the blood following meals. But gaps exist in understanding the precise molecular mechanisms by which insulin regulates glucose uptake in fat and muscle cells.

A research team led by Assia Shisheva, Ph.D., professor of physiology in Wayne State University's School of Medicine, has made breakthrough advancements on a molecule that may provide more answers to this mystery.

The conserved phospholipid enzyme, PIKfyve, was discovered in Shisheva's lab in 1999. Based on studies in cultured cells, the lab has implicated PIKfyve in the insulin-regulated glucose transport activation, which led to the development of a unique mouse model with PIKfyve ablation, or removal, in muscle (MPlfKO), the tissue responsible for the majority of postprandial glucose disposal.

In Shisheva's recent paper, "Muscle-specific PIKfyve gene distribution causes glucose intolerance, , adiposity and hyperinsulinemia but not muscle fiber-type switching," published online in the American Journal of Physiology - Endocrinology and Metabolism, Shisheva and her research team characterize whether this new model exhibits metabolic defects.

"Our team found a striking metabolic phenotype in the MPIfKO mice consisting of glucose intolerance and insulin resistance at an early age and on a normal diet," said Shisheva, a resident of Royal Oak. "We also revealed that PIKfyve is essential for normal insulin signaling to GLUT4/ in muscle and provided the first in vivo evidence for the central role of PIKfyve in the mechanisms regulating healthy , or ."

In addition, the research team found that these metabolic disturbances were followed by increased animal fat (adiposity) and elevated levels of insulin (hyperinsulinemia), but not abnormal amounts of lipids or cholesterol in the blood (dyslipidemia).

"The combined phenotype manifested by the MPlfKO mouse closely recapitulates the cluster of typical features in human prediabetes including systemic and insulin resistance, hyperinsulinemia and increased visceral obesity without dyslipidemia," said Shisheva.

"Therefore, our mouse model, in addition to providing novel mechanisms of insulin resistance, represents a valuable tool for exploring new preclinical strategies to improve treatments in individuals with prediabetes."

Related Stories

Telmisartan reverses insulin resistance in mice

date Jan 03, 2013

(HealthDay)—Treating mice fed a high-fat diet with telmisartan reverses insulin resistance and glucose intolerance, but only when the peroxisome proliferator-activated receptor-δ (PPAR-δ) gene is present, ...

Skipping breakfast may make obese women insulin resistant

date Jun 17, 2013

Overweight women who skip breakfast experience acute, or rapid-onset, insulin resistance, a condition that, when chronic, is a risk factor for diabetes, a new study finds. The results, which were presented Sunday at The Endocrine ...

Pot smoking linked to some metabolic changes

date Apr 19, 2013

(HealthDay)—Regularly smoking pot is associated with visceral adiposity and adipose tissue insulin resistance, but not other metabolic changes such as impaired β-cell function or hepatic steatosis, according ...

Recommended for you

Breathless: How blood-oxygen levels regulate air intake

date 10 hours ago

Researchers have unraveled the elusive process by which small, highly vascular clusters of sensory cells in the carotid arteries "taste the blood," as a 1926 essay put it—the initial step in regulating ...

Sex matters ... even for liver cells

date 11 hours ago

Female liver cells, and in particular those in menopaused women, are more susceptible to adverse effects of drugs than their male counterparts, according to new research carried out by the JRC. It is well ...

Caring for blindness: A new protein in sight?

date 12 hours ago

Vasoproliferative ocular diseases are responsible for sight loss in millions of people in the industrialised countries. Many patients do not currently respond to the treatment offered, which targets a specific ...

When genes are expressed in reverse

date 12 hours ago

Genes usually always be expressed as in Western writing: from left to right on the white canvas of our DNA. So when we speak of the activity of our genome, in fact we are referring to the expression of genes ...

Technique could speed biologic drugs

date 17 hours ago

Antibodies are specific molecules that can lock onto a particular cellular structure to start, stop or otherwise temper a biological process. Because they are so specific, antibodies are at the forefront ...

User 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.