Before defining insulin resistance, let’s explore why you should even care about this overlooked and misunderstood condition. Insulin resistance potentially affects up to 88% of adults in the US, with similar prevalence in various countries worldwide. Beyond its prevalence, insulin resistance is also profoundly relevant, acting as a fundamental cause in numerous serious chronic disorders, such as heart disease, diabetes, infertility, Alzheimer’s disease, and more. The actual term “insulin resistance” is somewhat inaccurate; at least when considered in the context of the human body, it fails to encompass some necessary nuance. All cells in the body respond to insulin—all of them. From liver to lungs, brain cells to bone—they all contain insulin receptors. These insulin receptors act as doors for insulin to come and “knock,” which then elicits an effect within the cell. The effect depends on the cell. In some cells, like muscle and fat, insulin stimulates glucose uptake—this is insulin’s most famous effect, but it’s far from its only job. Most cells in our body, such as those in the liver, don’t need insulin to pull in glucose, but they still need insulin to help them know what to do with nutrients like glucose and fat. But insulin also has other effects in numerous cells that have nothing to do with nutrients; its effects vary depending on the cell.
“The key features of insulin resistance are 1) blood levels of insulin are higher than they used to be, and 2) insulin doesn’t work as well at certain cells. The combination of these events explains why insulin resistance is connected to so many health disorders.”
When a cell loses its responsiveness to insulin, which can happen due to various conditions, it becomes insulin resistant. So, the term “insulin resistance” derives from the compromised insulin effect at the level of specific cells. This is one of the two pillars of insulin resistance: some cells don’t respond to insulin.
If we zoom out from the individual cells and view the entire body, we see the second pillar of insulin resistance: elevated insulin. Increased insulin, known as hyperinsulinemia, is both a cause and consequence of insulin resistance at cells. It’s also fundamental to many of the diseases associated with insulin resistance (more on that later). That too much insulin can cause insulin resistance is well established, including data from my own lab. Of course, as cells in the muscle or liver become insulin resistant, glucose levels rise (the muscles consume less glucose; the liver releases more glucose into the blood). In turn, this elevated glucose elicits a higher insulin level, which further drives insulin resistance.
Thus, the key features of insulin resistance are 1) blood levels of insulin are higher than they used to be, and 2) insulin doesn’t work as well at certain cells. The combination of these events explains why insulin resistance is connected to so many health disorders. Whereas the insulin-resistant cells barely respond, despite the elevated insulin, those cells that are still insulin sensitive are inundated with responding to insulin; they’re now over-stimulated.
Let’s look at some examples to understand better why this becomes such a problem. First, our muscle cells are among those that become insulin resistant. This has serious problems with glucose control, as muscles are responsible for consuming up to 80% of the glucose after a meal. In contrast, the ovaries’ theca cells remain insulin sensitive even as the muscles (and other cells) become insulin resistant. This creates a fascinating and tragic problem. Briefly, insulin normally acts to mildly inhibit the ovaries’ ability to convert testosterone into estrogens, but this conversion is always happening, and it’s essential for ovulation. However, with too much insulin, the sex hormone conversion is compromised, resulting in ovaries that are releasing too much testosterone and too little estrogens. This is the fundamental problem of polycystic ovarian syndrome (PCOS), the most common form of infertility in women. At its core, it’s a problem of too much insulin preventing the ovaries from doing what they’re supposed to do.
Now you know what too few do: what is insulin resistance and why it matters. In future posts, I’ll discuss its origins and what to do about it.