By Isha Antani
A rise in cheap fast food and a growing fascination with sugary, carbonated fizziness have bloated up today’s average Joe, who comes chock-full with a variety of illnesses thanks to his weight gain. Heart disease, stroke, and type 2 diabetes are only a handful of the diseases he suffers from. From the three listed, type 2 diabetes has received considerable attention in the last decade, partly due to the steep climb in the number cases of people getting the disease. The prevalence of type 2 diabetes has been increasing over the last few years and is predicted to affect 366 million worldwide by the year 2030.
Obesity and its attendant complications are on the rise in most developed and developing countries. In depth statistical analysis conducted to analyze the nature of this correlation concluded that that the increase in prevalence of diabetes is primarily blamed on the increase in obesity. While genetics and other medical conditions can give rise to the disease, diabetes caused by weight gain can be effectively prevented. It is not surprising therefore that researchers in the field have been vocal in urging the population to change its lifestyle triggering initiatives such as the replacement of junk food and sugar drinks in school cafeterias across America.
Current research is trying to elucidate the mechanisms of just how exactly obesity and diabetes are related. Both conditions share defects in the insulin signaling pathway that result in insulin resistance. Insulin resistance occurs when cells respond abnormally to insulin signaling, decelerating the uptake of glucose and ultimately leading to type 2 diabetes if it is not countered by weight loss and appropriate changes in lifestyle. Although many of the mechanisms in the insulin signaling pathway have been brought to light, its elaborate interconnectedness with other cellular pathways has made any comprehensive understanding quite difficult.
One of the other major pathways that is implicated in this obesity-diabetes link is the pro-inflammatory cytokine pathway. The production of several major cytokines, including leptin, TNF-alpha and interleukin-6, is upregulated in obesity. This increase creates a feedback loop that deactivates IRS1, a key player in the pathway via phosphorylation at a critical residue. This deactivation effectively terminates the insulin signaling cascade and closes the cellular gates that allow glucose uptake.
If everything was so clear cut, then an effective therapy for diabetes in obese individuals would already be available. Unfortunately the complex wiring of inter- and intra-cellular networks, raises multiple roadblocks blocking the level of understanding sufficient for the design of new therapies. Therefore, studies have yet to provide concrete answers. It is the hope that new methods of research, such as the use of predictive in-silico models, may yield the kind of definitive, mechanistic knowledge that is needed.
