In a ray of hope for diabetes patients, scientists have discovered the cellular sequence that leads to the trigger of the disease.They also found potential molecular targets for preventing or reversing the process.“We have described the etiology of obesity-related diabetes. We have pinpointed the steps, the way the whole thing happens,” said Jerrold M. Olefsky, a distinguished professor of medicine at University of California, San Diego.“The research on mice suggests that the processes are comparable in humans and these findings are important to not just understanding how diabetes begins, but how better to treat and prevent it,” he added.
During the study, the researchers fed mice a high-fat diet.
They observed that the abundant saturated fatty acids in the diet activated adenine nucleotide translocase 2 (ANT2) - a mitochondrial protein in fat cell membranes that is involved in cellular energy metabolism.Activation of ANT2 caused increased oxygen consumption, which meant less was available for the rest of the cell.The result was a relative state of hypoxia or inadequate oxygen supply.It subsequently induced production of a protective transcription factor in fat cells called HIF-1alpha.In turn, HIF-1alpha triggered release of chemokines, proteins that signal cellular distress, launching the immune system's inflammatory response.A sustained high-fat diet ensured that the process continued unabated, leading to obesity, chronic low-grade tissue inflammation and eventually, insulin resistance in the mice.
The elucidation of this sequence also revealed two potential therapeutic targets: ANT2 and HIF-1alpha.The researchers suggest that inhibiting either could blunt, or even reverse, the damaging cellular sequence.Diabetes is characterised by high blood sugar levels poorly regulated by either inadequate insulin production or because cells to not respond properly to the regulating hormone.The findings were published in the journal Cell.