The human brain is the most complex object in the known universe, but short on its heels is the intricate biochemical factory that regulates the functioning of the body – a variety of individual chemical processes that work together in prefect harmony. One of these chemical processes originates in the pancreas by producing insulin.
Insulin:
The pancreas is a gland located near the duodenum (the first part of the small intestine) which makes a few hormones, with insulin one of two principal hormones, the other being glucagon. When insulin is excreted into the bloodstream, it acts like a key in a lock to open the cells in the muscle, fat, and liver, to allow the transport of glucose into the cells, where it acts as the fuel to produce energy.
The insulin released by the pancreas increases after a meal, in response to the increase in plasma levels of glucose and amino acids. The increase of insulin secretion happens in two phases, with first-phase secretion consisting of a rapid burst of release to a high peak and then a steep decline to a low secretion rate. This phase takes place over a period of minutes. This is followed by second-phase secretion, consisting of a gradually increasing rate of secretion to a plateau level. The second phase occurs over an hour or more.
Glucose comes from the carbohydrates in the food that we eat. Carbohydrates get converted into glucose during the digestive process and absorbed into the bloodstream. When blood glucose levels rise, the pancreas releases insulin into the blood, facilitating the absorption of glucose into cells. In this way insulin lowers blood glucose levels to keep it in the normal range. When glucose levels are low, such as when fasting, the liver can make glucose to be used as fuel for energy.
Insulin not only plays a role in the metabolism of carbohydrates, but also in various processes in the metabolism of the other two macronutrients, fat, and protein. In lipid (fat) metabolism, insulin, for example, plays a role in the uptake of triglycerides from the blood into adipose (fat) tissue and muscle. In protein metabolism, insulin, for example, plays a role in the transport of amino acid into cells.
The other principal hormone secreted by the pancreas, glucagon, is the principal hormone involved in the prevention and counter regulation of hypoglycemia – a condition in which the blood sugar (glucose) level is lower than the standard range – by stimulating glucose production in the liver.
Insulin resistance:
For various reasons the harmony in which all the biochemical processes work can be disturbed, affecting the efficient functioning of the body. In the case of insulin, the cells in muscles, fat tissue and liver may stop responding well to insulin and become resistant to the key and lock effect of insulin and glucose. This results in a build-up of glucose in the bloodstream, which prompts the pancreas to secrete more insulin to help glucose enter the cells. Should the pancreas secrete enough insulin to overcome the weak response of cells to insulin, blood glucose levels will remain in the normal healthy range. When insufficient insulin for the amount of glucose in the bloodstream is secreted, the build-up of glucose remains in the bloodstream instead of entering the cells. Over time this can lead to prediabetes and type 2 diabetes.
Insulin resistance can be viewed as the inability of cells (resistance) to respond properly to normal circulating concentrations of insulin. To maintain a normal concentration of glucose in the blood, the pancreas compensates by secreting increased amounts of insulin. However, compensating for insulin resistance by an increase in insulin release is effective only temporarily. As insulin resistance increases, impaired glucose tolerance develops. Ultimately, failure or exhaustion of the pancreatic insulin producing cells results in a relative decrease in insulin secretion.
Prediabetes refers to blood glucose levels that are higher than normal, but not high enough to be diagnosed as diabetes.
Type 2 diabetes is the most common type of diabetes and happens when the pancreas doesn’t make enough insulin or when the body doesn’t use insulin well, resulting in high blood sugar levels. The combination of insulin resistance and impaired pancreatic cell function characterizes clinical type 2 diabetes. Insulin resistance precedes type 2 diabetes by several years.
Type 1 diabetes is a chronic autoimmune disease in which the immune system for some unknown reason attacks and destroys the insulin-producing cells in the pancreas.
How do you know you have insulin resistance?
If the pancreas can supply enough insulin to keep blood glucose levels within the normal range, you usually won’t be aware that you have insulin resistance, at least not by how you feel or look. Insulin resistance can get worse over time and the cells which make insulin in the pancreas can exhaust. When the pancreas becomes unable to produce enough insulin, the resulting elevated blood glucose levels (hyperglycemia) would show symptoms.
Symptoms of high blood sugar include slow-healing cuts and sores, increased thirst and hunger, blurred vision, vaginal and skin infections, and headaches.
When insulin resistance is suspected without any obvious symptoms, blood tests are the only way to confirm the condition.
Causes of insulin resistance:
Scientists have identified several genes that may play a role in making a person prone to develop insulin resistance, while age plays a role, as older people are more likely to develop insulin resistance. However, scientists believe that the two main contributing causes to insulin resistance are physical inactivity and excess body fat, especially around the belly.
Obesity: A primary cause of insulin resistance is obesity, especially excess body fat in the belly and around the organs, which is called visceral fat. Studies have found that belly fat makes hormones and other substances, which may contribute to long term inflammation in the body, playing a role in insulin resistance. Interestingly, elevated levels of insulin can cause weight gain, which makes insulin resistance worse.
Physical inactivity: A lack of physical activity can cause insulin resistance, as physical activity makes the body more sensitive to insulin and by building muscle can help to absorb blood glucose. As a lack of physical activity, along with a sedentary lifestyle, can lead to weight gain, contributing to insulin resistance.
Diet: A diet high in carbohydrates, saturated fats, and highly processed foods have been linked to insulin resistance, as these foods are digested quickly and cause blood sugar levels to spike, requiring lots of insulin. Over time this leads to insulin resistance.
Medication: Certain medications may cause insulin resistance, such as steroids, certain blood pressure medications, certain HIV treatments, and some psychiatric medications.
Hormonal disorders: Certain hormonal disorders can influence how well the body uses insulin and can cause insulin resistance, for example when the thyroid is underactive (hypothyroidism) and doesn’t produce enough thyroid hormone, it can slow down metabolism, including glucose metabolism, leading to insulin resistance.
How is insulin resistance treated?
Lifestyle modifications are the main treatment possibilities to reverse insulin resistance, as factors such as genetic predisposition and age cannot be treated. Treatment and prevention of insulin resistance should address the primary causes, namely by getting to a healthy weight, embarking on a physical activity programme of at least 30 minutes a day of moderate activity such as brisk walking, and eating a healthy diet.
Conclusion:
Scientists still need to discover much about the development of insulin resistance. What is clear from the studies is that obesity, in particular excess belly fat, lack of physical activity, and an unhealthy diet are the main contributing factors to insulin resistance. Interestingly, over the past decade scientists have linked obesity during midlife as a major risk factor for developing Alzheimer’s and other related dementia.
The three major risk factors for the development of insulin resistance are fortunately all modifiable through lifestyle changes around eating, physical activity, and weight management.
References:
Insulin resistance. Reviewed 23 June 2021. WebMD. (www.webmd.com)
Insulin resistance. Reviewed 16 December 2021. Cleveland Clinic. USA. (www.clevelandclinic.org)
What to know about insulin resistance. Updated 17 June 2021. Endocrineweb. (www.endocrineweb.com)
Insulin resistance and prediabetes. Reviewed May 2018. National Institute of Diabetes and Digestive and Kidney Diseases. National Institutes of Health. USA. (www.niddk.nih.gov)
Insulin resistance & diabetes. Reviewed 10 August 2021. Centers for Disease Control and Prevention. (www.cdc.gov)
Medical Physiology. A systems approach. (Physiology Handbook). By Hershell Raff, Michael Levitzky, et al. Published 2011. McGraw Hill Medical. P 786.
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