For the overwhelming majority of sufferers, type 2 diabetes is a lifestyle disease. It is something that they did to themselves, and which could be turned back at near any point with a suitable (albeit increasingly drastic) change in diet and lifestyle. Giving yourself the highest chance of avoiding type 2 diabetes is easy: stay active and stay thin. Nonetheless, the medical research community spends a lot of time and effort on finding ways for people to remain fat and indolent while still avoiding diabetes - though of course these efforts also apply to the much smaller population unfortunate enough suffer the condition regardless.
Here researchers find a way to protect the small population of insulin generating beta cells impacted by the mechanisms of type 2 diabetes, but by the sounds of it this will not affect any of the numerous other consequences of becoming fat, such as a raised risk of suffering all of the other common age-related conditions.
An enzyme called 12-LO promotes the obesity-induced oxidative stress in the pancreatic cells that leads to pre-diabetes, and diabetes. 12-LO's enzymatic action is the last step in the production of certain small molecules that harm the cell. The findings will enable the development of drugs that can interfere with this enzyme, preventing or even reversing diabetes. In earlier studies, these [researchers] showed that 12-LO (which stands for 12-lipoxygenase) is present in these cells only in people who become overweight.
The harmful small molecules resulting from 12-LO's enzymatic action are known as HETEs, short for hydroxyeicosatetraenoic acid. HETEs harm the mitochondria, which then fail to produce sufficient energy to enable the pancreatic cells to manufacture the necessary quantities of insulin.
For the study, the investigators genetically engineered mice that lacked the gene for 12-LO exclusively in their pancreas cells. Mice were either fed a low-fat or high-fat diet. Both the control mice and the knockout mice on the high fat diet developed obesity and insulin resistance. The investigators also examined the pancreatic beta cells of both knockout and control mice, using both microscopic studies and molecular analysis. Those from the knockout mice were intact and healthy, while those from the control mice showed oxidative damage, demonstrating that 12-LO and the resulting HETEs caused the beta cell failure. "Our research is the first to show that 12-LO in the beta cell is the culprit in the development of pre-diabetes, following high fat diets. Our work also lends important credence to the notion that the beta cell is the primary defective cell in virtually all forms of diabetes and pre-diabetes."