What Causes Insulin Resistance? Part III

As discussed in previous posts, cellular energy excess and inflammation are two important and interlinked causes of insulin resistance.  Continuing our exploration of insulin resistance, let's turn our attention to the brain.

The brain influences every tissue in the body, in many instances managing tissue processes to react to changing environmental or internal conditions.  It is intimately involved in insulin signaling in various tissues, for example by:

• regulating insulin secretion by the pancreas (1)
• regulating glucose absorption by tissues in response to insulin (2)
• regulating the suppression of glucose production by the liver in response to insulin (3)
• regulating the trafficking of fatty acids in and out of fat cells in response to insulin (4, 5)

Because of its important role in insulin signaling, the brain is a candidate mechanism of insulin resistance.

Read more »

What Causes Insulin Resistance? Part II

In the last post, I described how cellular energy excess causes insulin resistance, and how this is triggered by whole-body energy imbalance.  In this post, I'll describe another major cause of insulin resistance: inflammation. 

Inflammation

In 1876, a German physician named W Ebstein reported that high doses of sodium salicylate could totally eliminate the signs and symptoms of diabetes in certain patients (Berliner Klinische Wochenschrift. 13:337. 1876). Following up on this work in 1901, the British physician RT Williamson reported that treating diabetic patients with sodium salicylate caused a striking decrease in the amount of glucose contained in the patients' urine, also indicating an apparent improvement in diabetes (2).  This effect was essentially forgotten until 1957, when it was rediscovered.

Read more »

What Causes Insulin Resistance? Part I

Insulin is an ancient hormone that influences many processes in the body.  Its main role is to manage circulating concentrations of nutrients (principally glucose and fatty acids, the body's two main fuels), keeping them within a fairly narrow range*.  It does this by encouraging the transport of nutrients into cells from the circulation, and discouraging the export of nutrients out of storage sites, in response to an increase in circulating nutrients (glucose or fatty acids). It therefore operates a negative feedback loop that constrains circulating nutrient concentrations.  It also has many other functions that are tissue-specific.

Insulin resistance is a state in which cells lose sensitivity to the effects of insulin, eventually leading to a diminished ability to control circulating nutrients (glucose and fatty acids).  It is a major contributor to diabetes risk, and probably a contributor to the risk of cardiovascular disease, certain cancers and a number of other disorders. 

Why is it important to manage the concentration of circulating nutrients to keep them within a narrow range?  The answer to that question is the crux of this post. 

Read more »