Written by Tonya Mukherjee and Edited by Kevin Liu
More than 34 million Americans have diabetes, and of those 34 million, 90-95% are afflicted with type II diabetes. Type II diabetes is characterized by insulin resistance within the body [1]. Ostensibly, studies show that some people may have a likelihood of developing diabetes due to genetic reasons; however, studies suggest that environmental factors such as obesity are largely linked to insulin resistance.
Obesity is becoming increasingly common in America; in fact, as of 2019, 40% of adults over the age of 20 were considered obese [1]. Obesity is measured primarily through an individual’s body mass index (BMI), which calculates body size by measuring weight in proportion to height. Although other factors can lead to high BMI such as large muscle or bone density, obesity is still a well-known and increasingly commonplace issue in America. And with obesity comes a large number of health problems, including type II diabetes.
Blood sugar conversion into either fat or energy is regulated by insulin. Insulin is a hormone made by the pancreas. It is responsible for allowing sugar to enter the cells of the body to be used for energy or stored as fat. Insulin resistance is characterized by cells not responding to insulin normally, and so blood sugar is not utilized by the body, thus increasing blood sugar levels [1].
Obesity is linked with the formation of enlarged fat cells, which are resistant to glucose uptake. Pre-fat cells, cells which have the ability to specialize into different kinds of cells, typically differentiate into muscle or organ tissue. However, mature and enlarged fat cells are unable to differentiate, as they are already specialized to contain excess calories; thus, until large fat cells are broken down to create energy, they continue to mass release free-fatty acids. This ultimately contributes to higher levels of free-fatty acid content in the body [2]. Higher levels of free-fatty acid can result in the overexpression or underexpression of certain cellular signals, such as the p53 signal [3].
Studies have shown that disturbed levels of p53 are involved in insulin resistance and diabetes in numerous ways. P53 is a tumor suppressor signal, meaning it is responsible for turning cellular pathways off and killing unusable or damaged cells. It is, essentially, a regulator of metabolic balance [2]. Free-fatty acids can work upstream of p53 pathways to increase p53 production. Although p53 is responsible for removing damaged and unusable cells, a high p53 content often results in the p53-induced death of healthy pancreatic cells. This damages the pancreas and decreases insulin secretion [3,2,5]. Ultimately, the decrease in insulin production results in higher blood sugar levels and the development of type II diabetes. Studies in animals have also shown that p53 may be responsible for the overexpression of signals involved with inhibiting cell glucose transporters, which leads to less sugar traveling into cells [3,2,5]. Sugar thus either remains in the blood, or it is converted into fat for storage. High blood sugar and free-fatty acid levels eventually cause the blood to become toxic, which results in a variety of health problems and diseases, including type II diabetes [2].
Prediabetes, a condition which often comes before type II diabetes, is associated with toxic glucose and lipid levels that cause DNA damage and increase p53 activation [3]. DNA damage leads to a variety of health problems, as DNA is responsible for creating cellular signals for metabolic pathways. Increases in p53 levels lead to more cell death, which results in organ damage that contributes to conditions such as insulin resistance [2,3,5]. In fact, as of 2014, almost 90% of obese adults with type II diabetes developed non-alcoholic fatty liver disease, a disease which corresponds with liver cell damage and high liver fat content. Essentially, factors such as obesity harm p53 proteins, which are responsible for inhibiting and regulating a variety of important metabolic pathways. However, animal studies show that decreasing the size of fat cells regulates p53. Ultimately, many studies suggest that losing weight is the best way to decrease blood sugar levels, rehabilitate cellular pathways, and even cure type II diabetes [2,3,5].
References:
- “Type 2 Diabetes.” Centers for Disease Control and Prevention, U.S. Department of Health & Human Services, 30 May 2019, https://www.cdc.gov/diabetes/basics/type2.html.
- Heilbronn, L., Smith, S. R., Ravussin, E. (2004). Failure of fat cell proliferation, mitochondrial function and fat oxidation results in ectopic fat storage, insulin resistance and type II diabetes mellitus. International Journal of Obesity and Related Disorders, 28:12–21.
- Kung, C., Murphy, E.M., (2016). The role of the p53 tumor suppressor in metabolism and diabetes. The Journal of Endocrinology, 231:61–75.
- Perry, J.R., Samuel, T.V., Petersen, F.K., Shulman, I.G. (2014). The role of hepaticlipids in hepatic insulin resistance and type 2 diabetes. Nature, 510:84–91.
- Strycharz, J., Drzewoski, J., Szemraj, J., Sliwinska, A. (2017). Is p53 Involved in Tissue-Specific Insulin Resistance Formation? Hindawi, 2017:1–16.