Metabolic HealthPart 1 of a series

Introduction to Insulin Resistance and Chronic Metabolic Disease

The excess of endogenous insulin our body releases in response to food — and the inability to properly respond to that insulin over time — is the phenomenon that fuels the majority of problems we associate with the failing health of the modern person.

Dr. Dante Paredes

DO · Texas Licensed Physician · Co-Founder, Olympus Health

Published

April 1, 2026

Read time

12 min

Introduction to Insulin Resistance and Chronic Metabolic Disease

The heart of our work is in education. Consequently, aside from the clinical work we do, we make it a point to spend time teaching how your body works so that you can better navigate your health — with or without us. This article will be the first of a multi-part series covering metabolic syndrome. This topic was selected because the excess of endogenous insulin that our body releases in response to food — along with the inability to properly respond to that insulin over time — is the phenomenon that fuels the majority of problems we routinely associate with the failing health of the modern person.

📖 Primary source: Much of what follows is an overview of extensive research by Dr. Gerald Shulman. Full citation: pmc.ncbi.nlm.nih.gov/articles/PMC6170977

Key Concepts — Start Here

In this first lesson let's start by introducing some of the key pieces of information that you'll need to know as we move forward. Understanding these players will make everything that follows click into place.

Insulin

This is the hormone released by your pancreas in response to food. You get some of it no matter what you eat, but you release a particularly large amount when eating something rich in carbohydrates. When released into the body it activates various systems that, taken altogether, essentially put the body into a setting where it is ready to absorb nutrients from the gut, build new structures, and put any excess material into storage. It is the hormone of "plenty" and "surplus." For it to do its job, insulin has to bind to an insulin receptor embedded into the surface of a cell.

Glucagon

This is the hormone released by your pancreas in response to a general lack of food, exercise, and — oddly enough — protein-rich meals. When released, it activates systems that put the body into a setting to use up stored fuels (carbohydrates and fat) to sustain us during periods where energy demands are not being met. It is also responsible for activating AMPK — a cellular signal responsible for activating the repair and recycling systems of the body.

The Pancreas

This is the organ of digestion. It releases enzymes — specialized proteins that perform the function of breaking down food into smaller bits that our bodies can absorb and use. It is also responsible for releasing the signaling hormones insulin and glucagon that prepare the body for taking in nutrition and using stored fuels respectively.

The Liver

This organ has two essential functions we will highlight: detoxification and supply chain management. The liver receives everything taken from your gut and processes it so that it can safely enter the rest of the body. It is also responsible for much of the labeling and shipping of these materials to their target destinations. It has some limited storage capacity in the form of glycogen and can function as the storage site of last resort in the presence of dangerously high fuel levels. Lipoproteins and cholesterol are made and processed here.

Adipose (Fat Tissue)

This is the proper name for the distributed organ made up of our fat cells. They contain little storage depots called vacuoles whose job is to safely store materials for future use. Adipose is meant to safely house large amounts of fat over an extended period of time. When food is scarce and glycogen reserves are close to depleted, adipose is what keeps everything running by supplying fats and glycerol which can then be converted into glucose. Everyone has a certain limit of how much fat they can safely store before it begins to spill out into other systems. Adipose also performs a hormonal function, taking part in the regulation and synthesis of estrogen in both men and women. It comes in two broad categories: subcutaneous (deposited around limbs, abdomen, and face — visible) and visceral (surrounding our organs, not directly visible — the dangerous kind when excess accumulates).

Skeletal Muscle

Whether it's dialing up or down the diameter of blood vessels, pumping blood throughout the body, or moving the body through the environment, muscle tissue — made up of cells called myocytes — is responsible for our body's capacity to move. It is fueled by glucose and fat and has limited storage capacity in the form of glycogen. It is one of the few organs that can absorb glucose without insulin.

Carbohydrates

One of three primary macronutrients that our body needs to survive. Carbohydrates can be found in a variety of forms but ultimately they are broken down into a simple sugar called glucose that can then be absorbed into our blood. When the body receives carbohydrates from a meal it releases insulin into the blood to let our various cells know to open the gates and let the glucose in. Note that except for very clear exceptions, our body needs the signal provided by insulin in order to take glucose from the blood and transfer it into a cell. Diabetes is the state in which the body can no longer put the sugar from the blood into a cell — and therefore it stays in the blood, wreaking all sorts of havoc.

Protein

One of three primary macronutrients that our body needs to survive. Proteins are long bundles of smaller molecules called amino acids, folded into little biological machines to do work or provide structure. Similar to how cities need routine maintenance and rebuilding, our body breaks down and replaces structures and machinery as they wear out. Because of this constant need to replace, repair, and renew, we need to consume protein regularly in order to not break down. Our body makes many of its proteins on its own but we need certain essential amino acids from the diet because we lack the machinery to make them internally.

Fats

One of three primary macronutrients that our body needs to survive. Fats, like protein and carbohydrates, are used as both fuel and building material. Fat provides a compact, energy-dense source of energy for long-term storage. It also provides the basic material for synthesizing hormones and the cell membranes we need to maintain in order to not spontaneously turn to soup. Fats can be found in the form of free fatty acids or bundled together in groups of three, in which case they are called triglycerides. Because fat does not readily dissolve into the bloodstream, prior to leaving the liver fat gets packaged into lipoproteins along with cholesterol. These lipoproteins you may recognize from bloodwork by their names: LDL, HDL, and VLDL.

Sound familiar?

If this resonates — we may be the right fit.

Book a free 15-min call. No pressure, just an honest conversation.

Book Free Call

What Happens After You Eat?

Note that the process outlined below will be deliberately simplified for clarity. In truth many of these systems are less sequential than they appear and more like various processes colliding at different intervals. For the sake of factoring out the beautiful chaos that is biochemistry, I am making a choice to present the steps with a focus on the key players mentioned above.

After you swallow a bolus of food it travels down the esophagus into your stomach. Once in the stomach the food is churned up, broken down, and mixed with gastric juices and enzymes in order to become a sort of homogenized liquid that can be steadily siphoned into the small intestine. As food enters the small intestine it mixes with other juices released by your pancreas in order to be ready for absorption into the blood. Parallel to this process the pancreas is also releasing insulin into the bloodstream so that it has time to reach all of our various tissues so that they're ready to receive the incoming delivery of resources. With insulin in the blood the body is set up to take in all the good stuff — with preference given first and foremost to the brain, followed by muscle, then all the other organs, then adipose.

After the food slurry gets absorbed by the intestines it first goes to the liver for filtration and processing. The liver takes some small cut of what's available to fuel itself then pushes the remainder along into the bloodstream. At this point the carbohydrates from your meal are now freely floating in the blood as glucose. The fat from your meal, bundled together with cholesterol inside of lipoproteins like LDL, is also released into the blood so that it can be picked up by whatever tissues need it.

Skeletal muscle is tremendously hungry for glucose and takes a large portion of the available sugars. On the surface of the muscle cell there are insulin receptors set up so that when insulin molecules make contact, it triggers a cascade that results in the cell activating proteins called GLUT4 receptors — specialized gateways that traffic glucose into the cell. Note that without insulin and insulin receptors, most cells do not have a way to take in glucose. The skeletal muscle takes that glucose to make ATP — the actual final form of our fuel that is ready to use. Once it has enough ATP, the muscle takes a bit more glucose and converts it into a stable storage form called glycogen. Once ATP and glycogen stores are topped off, the individual myocytes begin to deactivate their GLUT4 receptors so that some other hungry cell can get its share.

This process continues on with minor variation for each cell in our body. Once the body is topped off and acute energy demands are met, the excess fuel goes back to the liver where it can be made into fat and glycogen for storage — then once again shipped out into the blood to reach its long-term storage site: adipose.

When the Tank Is Full

In adipose it is honestly much of the same story. Insulin hits the adipocyte, IRS signaling proteins activate GLUT4, GLUT4 facilitates the entry of glucose while lipoproteins incorporate into the cell membranes. All is good and well…

“…until there is no more room.”

In the same way that muscle tissue gets full and shuts down the ability to take in more sugar, our fat cells also reserve that capacity. The fat cell simply has far greater capacity to hold and store than muscle — but a "far greater capacity" is not the same as an infinite capacity.

Consider the similarities between oil and natural gas of industry with the fat and carbohydrates that fuel our bodies. All of these fuels are hydrocarbons — and both are prone to oxidation which, as it occurs, can damage surrounding structures if the reaction occurs chaotically. In the same way combusting oil and natural gas releases energy to perform meaningful work, oxidizing fats and sugars releases energy which we use to perform meaningful work. In the same way that oil and natural gas need to be safely processed, transferred, and burned in order to harness their energy — our fats and sugars have to be processed carefully so that all that stored energy is directed towards meaningful processes rather than chaotically burning up our tissues.

“In the same way that combustion sets our fuels aflame, oxidation — when it occurs inside us — creates regions of inflammation. Sometimes English is cool.”

When our body starts to lose the space to safely store fat and glucose, it starts to resist the insulin signal. This process occurs locally such that "hungry" tissues are sensitive and "fed" tissues are resistant. That being said, when the entire body is topped off and collectively saying "we're good" — that brings us to the situation where we have all this fuel floating around with nowhere to go.

↓ The presence of excess fuel with nowhere to go — and the various maladaptive events that follow — will be the focus of Part 2. We will continue the story and walk through how the body tries to work around all this fuel, and how those processes create the common pathway that connects high blood pressure, heart disease, diabetes, obesity, and fatty liver disease into the meta-problem that is metabolic syndrome.

Written by

Dr. Dante Paredes

DO · Texas Licensed Physician · Co-Founder, Olympus Health

Martial arts practitioner, StrongFirst kettlebell instructor, and physician focused on metabolic health and performance medicine. Dr. Dante writes about the intersection of clinical medicine, movement, and the science of building a body that lasts.

Ready to work with the doctors behind the writing?

Book a free 15-minute call. No pressure — just an honest conversation about whether we're the right fit.

Book Your Free 15-Min Call

Texas residents only. Limited spots available.

Introduction to Insulin Resistance and Chronic Metabolic Disease

Key Concepts — Start Here

What Happens After You Eat?

When the Tank Is Full

More from the blog

On Motivation and Meaning in the Mundane

It's Not Your Fault

More articles on the way

Ready to work with the doctors behind the writing?