Glucose homeostasis is of critical importance to human health due to the central role of glucose as a source of energy. Abnormalities in the regulation and metabolism of glucose are common symptoms or risk factors for a range of metabolic diseases.
In the mitochondria of cells is where the metabolism of glucose is completed, and energy, in the form of ATP, is produced. The 18 kiloDalton Translocator Protein (TSPO) is a protein found on the mitochondria in the cells of a number of organs and tissues involved in glucose regulation. Nicotinamide nucleotide transhydrogenase (Nnt) is a gene which encodes for transhydrogenase protein. An integral protein of the mitochondria and its function.
A number of studies within animals have shown that TSPO and Nnt to be important in glucose regulation and metabolism. In Zebrafish, two different drugs which interact with TSPO lowered blood sugar levels. Furthermore, in Mice, one of these drugs lowered fasting blood sugar for up to four hours. In obese mice that were fed a high fat diet, this same drug after being consumed for four weeks, also improved glucose regulation and reduced liver fat. In obese mice fat cells, TSPO has also shown to be found in lower levels than normal mice. Also, within mice, absence of the Nnt gene has been associated with glucose intolerance, defective insulin secretion and higher inflammation. However, understanding within humans is limited.
We aim to use the data available from the UK Biobank to determine the role of TSPO and NnT in glucose regulation and metabolism in humans. Through identifying associations between TSPO, NnT and glucose regulation and metabolism, this project will support a translational step to develop novel therapeutic approaches to glucose regulation in humans.