New Molecule Mimics Exercise, May Help Diabetics

Diabetes mellitus is a disease that affects an estimated 390 million people worldwide, with that figure expected to rise by over 50% by 2035. This potentially deadly ailment results in the failure of glucose to reach the interior of cells to be processed for energy, and is most commonly found in two closely linked forms. In type 1 diabetes (DM1), the pancreas ceases to produce insulin, the hormone responsible for triggering cellular glucose uptake. In type 2 diabetes (DM2), the issue is that the cells become insensitive to the presence of insulin. While DM1 is most commonly caused by an autoimmune response, DM2 is generally, but not always, caused by poor diet and obesity.

Exogenous insulin is required for the control of DM1, whereas medication for DM2 centres on drugs that serve to lower blood sugar, and increase cellular uptake. Roughly two-thirds of DM2 sufferers are put on at least one drug, with the most common being metformin. One job that metformin does well is to reduce glucose production in the liver, which is up-regulated in diabetes, primarily as a response to low intracellular glucose levels. Metformin’s other mechanism, the increased cellular uptake of blood sugars, is not fully understood. However, the mechanism most favoured by theorists is the increased activation of AMP-activated protein kinase (AMPK), and there is some evidence to support this.

The formation of adenosine triphosphate (ATP) is the end goal of all energy systems, and it is the breakdown of this molecule that allows the body to function. ATP is eventually cleaved to ADP, and then AMP (Adenosine diphosphate and monophosphate, respectively) before being re-phosphorylated back to ATP. AMPK is a heterotrimeric enzyme that plays a key role in the regulation of many catabolic (energy producing) processes, including cellular glucose uptake. Activation of AMPK is primarily triggered by an increase in the AMP:ATP ratio, which is essentially an indicator of cellular starvation. It is believed that mysterious metformin activates AMPK by increasing the concentration of cytosolic AMP.

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Sasha Perkins

Administrative Assistant and Journalist at the Pluto Daily since 2012.