Insight into the cell biology of diabetes

When energy intake is chronically higher than expenditure, the surplus energy is stored in adipose tissue, leading to obesity. Obesity is a risk factor for diabetes, the condition associated with high blood glucose levels and reduced insulin production.

In healthy people, insulin maintains blood sugar levels at physiological levels. In obese patients, however, insulin cannot sufficiently reduce blood sugar levels, a condition known as insulin resistance. This progressively results in insufficient amounts of insulin and then diabetes.

Currently there is no therapy for obesity or diabetes. However, recent evidence points towards the ability of several gut hormones including glucagon-like peptide 1 (GLP1) to control body weight and blood glucose levels. These hormones are secreted from specialised intestine cells (L-cells) after a meal, and act on several tissues including the brain and the pancreas to signal incoming energy. GLP1-like agonists or inhibitors of GLP1-degrading enzymes are currently used as treatments for diabetes.

The EU-funded TRAFALOGY (Functional analysis of transcription factors in L-cell biology) project aimed to characterise the L-cells in terms of gene and protein expression. Scientists performed an in vitro screen to define potential regulators of L-cell mitosis, apoptosis, differentiation and GLP1 secretion. The results verified the ability of fatty acids to stimulate GLP1 secretion in vitro, and also identified several potential regulators of these processes.

Scientists performed overexpression studies to gain insight into the function of candidate genes as well as the molecular mechanisms controlling their activity. Τhe data gained by these experiments may help to define critical pathways affecting function and viability of these metabolically important cells.

Apart from invaluable insight into L-cell biology, the findings of the TRAFALOGY study will assist in the development of novel therapeutics for treating obesity and diabetes.