It has long been known that obesity is related to the development of type 2 diabetes. Why obesity causes diabetes is a question researchers are attempting to answer on the cellular level. It has been proven that upper-body obesity correlates strongly with insulin resistance and metabolic syndrome. Upper-body fat can accumulate in visceral fat or subcutaneous fat, releasing nonesterified fatty acids from adipose tissue (fat) contributing to the accumulation of lipids in other tissues in the body. Adipose tissue in obese people is insulin resistant worsening insulin resistance in muscle and altering hepatic metabolism. Insulin resistance paired with pancreatic beta-cell malfunction results in a failure to regulate blood glucose levels.
Why Obesity Causes Diabetes – Inflammation
The immune and metabolic systems have evolved together, with their functions closely related. Energy is needed to fight infection and many of the same cellular mechanisms function for both systems. Thus, metabolic imbalance (due to starvation or obesity) is thought to create imbalance in the immune system. Obesity is known to cause chronic low-level inflammation and stress in the body causing adipose tissue to release cytokines that can inhibit insulin function. Lipids are also related to obesity and insulin function with high levels indicating infection and inflammation, and is responsible for tissue insulin resistance and dylipidemia. Furthermore, macrophages are found in the adipose tissue of obese people, contributing to inflammation leading scientist to speculate about their role in insulin resistance. Inflammation and stress also interfere with the pathways of insulin receptors. This same process is seen to occur by a signaling of cells due to stress due to obesity. This endoplasmic reticulum (ER) stress furthers inflammation and insulin resistance in tissue.
Why Obesity Causes Diabetes – Transcription Factors
A joint study by the University of California Santa Barbara (UCSB) and Sanford-Burnham Medical Research Institute published in August 2011, found a link between high-fat diets and the onset of diabetes. The study, done in mice and humans, discovered a pancreatic “pathway” in beta-cells that can lead to metabolic defects in other organs such as the liver and adipose tissue. Researchers found that high levels of fat interfered with two transpiration factors FOXA2 and HNF1A that are required for the production of the enzyme glycosyltransferase (GnT-4a) that modifies proteins with a particular sugar structure. Retention of glucose transporters in cells depends on GnT-4a which in turn relies on FOXA2 and HNF1A. When mice were fed a high-fat diet they lost function of their beta-cells however, when GnT-4a was functioning, even in obese animals, diabetes was prevented. An understanding the effects of excess calorie and fat consumption can help in the development of treatments.
