Is Insulin Resistance A Natural Defense Against Overnutrition?

When we eat, we make glucose available to our cells for energy and other processes. Insulin helps that glucose enter our cells. But when cells reach a certain satiety point, insulin's signaling ability lessens, possibly protecting the cell from an influx of too much glucose. This process may be at the root of insulin resistance.



A study that appeared in the February 21 issue of Nature described a link between the presence of glucose, fats, and other nutrients in the bloodstream ... and the action of an enzyme called O-linked beta-N-acetylglucosamine transferase (OGT). When nutrient levels are high, OGT travels out of the cell nucleus to the cell membrane. There it works to dampen insulin signaling by attaching glucose-containing molecules to key proteins of the intercellular insulin signaling pathway.

Not surprisingly, the particular sugar molecule it attaches is called O-linked beta-N-acetylglucosamine (O-GlcNAc). And the amount of O-GlcNAc is related to how much glucose is in the bloodstream.

Knowing the specific enzymes and sugars involved in insulin resistance can lead to the development of specific drugs that target these molecules. This type of research can also help us to understand how overnutrition can bring about insulin resistance, a condition which often leads to diabetes.

Although drug therapy that targets these molecules may not be available for a while, diet therapy is available today. Learning how to feed our bodies just what they need, but not more than they need, can improve the action of insulin ... reducing the occurrence of insulin resistance and lowering the risk for type 2 diabetes.
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For the study:
Phosphoinositide Signalling Links O-Glcnac Transferase To Insulin Resistance

News article (ScienceDaily):
Novel Link Between Excessive Nutrient Levels And Insulin Resistance Uncovered

Fat Cells Help Pancreas To Secrete Insulin

According to researchers from Washington University in St. Louis, fat cells - at least those in mice - release a protein, called Nampt, that helps the beta cells of the pancreas secrete insulin.

"In the face of increasing insulin resistance," says lead author Shin-ichiro Imai, "this process could be critical for compensating pancreatic beta cell function."

So why do people who are overweight have difficulty metabolizing glucose? Dr. Imai says,

"It may be that in some obese individuals a threshold has been reached so that this mechanism no longer provides adequate compensation. But there may be ways to overcome this threshold."

Those ways involve a compound produced by Nampt, called NMN. NMN circulates in the bloodstream. When it reaches the pancreas in high enough amounts, it stimulates insulin secretion. Mice that were short on Nampt had impaired glucose metabolism, a condition that improved when they were given NMN.

This discovery could lead to new ways of treating insulin resistance and diabetes.
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The study was reported in the November 7 issue of Cell Metabolism:
Nampt/PBEF/Visfatin Regulates Insulin Secretion in β Cells as a Systemic NAD Biosynthetic Enzyme

Washington University news brief:
Fat Cells Send Message That Aids Insulin Secretion

Photo of four fat cells, from immaturity to full maturity, via University of Medicine and Dentistry of New Jersey: UMDNJ Magazine

Less Insulin, Longer Life

It's not that we don't need insulin...

When there is a depletion or absence of insulin, as seen with type 1 diabetes, glucose from food cannot easily leave the bloodstream and enter cells. Hyperglycemia or high blood sugar results. In this case, too little insulin is detrimental.

But too much insulin can also be detrimental...

A study appearing in this month's Science magazine found that mice with less of a molecule called insulin receptor substrate 2 (IRS2) (a signaling molecule that is turned on by circulating insulin) lived 18% longer than normal control mice. Interestingly, this benefit was seen regardless of the fact that mice were overweight and glucose intolerant.¹

What causes higher levels of insulin? One cause is insulin resistance, a state in which cells fail to respond properly to insulin. When cells are resistant, the pancreas will secrete more insulin to compensate. Insulin resistance often accompanies or precedes type 2 diabetes.

From an interview with Reuters News:²

"The researchers note that people who live to be 100 or more often have reduced insulin levels and their cells show better insulin sensitivity."

What can you do to improve your insulin sensitivity, lessening the amount of insulin you secrete?

• Lose weight if needed.
  
• Increase physical activity.
  
• Monitor your carbohydrate intake and limit overly refined and processed grains.

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¹ Brain IRS2 Signaling Coordinates Life Span and Nutrient Homeostasis
² Key To A Long Life - Less Insulin In The Brain