Attenuation of streptozotocin-induced pancreatic beta cell death in transgenic fat-1 mice via autophagy activation.

BACKGROUND

The incidence of diabetes has rapidly increased due to changes in eating habits. Inflammatory factors and beta (β) cell dysfunction due to high-fat diets aggravate chronic diseases and their complications. However, omega-3 dietary fats have anti-inflammatory effects, and the involvement of autophagy in the etiology of diabetes has been reported. Therefore, we examined the protective effects of autophagy on diabetes using fat-1 transgenic mice with omega-3 self-synthesis capability.

METHODS

Streptozotocin (STZ) administration induced β cell dysfunction in mice; blood glucose levels and water consumption were subsequently measured. Using hematoxylin and eosin (H&E) and Masson's trichrome staining, we quantitatively assessed STZ-induced changes in the number, mass, and fibrosis of pancreatic islets in fat-1 and control mice. We identified the microtubule-associated protein 1A/1B light chain 3-immunoreactive puncta in β cells and quantified p62 levels in the pancreas of fat-1 and control mice.

RESULTS

STZ-induced diabetic phenotypes, including hyperglycemia and polydipsia, were attenuated in fat-1 mice. Histological determination using H&E and Masson's trichrome staining revealed the protective effects of the fat-1 mutation on cell death and the scarring of pancreatic islets after STZ injection. In the β cells of control mice, autophagy was abruptly activated after STZ treatment. Basal autophagy levels were elevated in fat-1 mice β cells, and this persisted after STZ treatment. Together with autophagosome detection, these results revealed that n-3 PUFA enrichment might partly prevent the STZ-related pancreatic islet damage by upregulating the basal activity of autophagy and improving autophagic flux disturbance.

CONCLUSION

Fat-1 transgenic mice with a n-3 PUFA self-synthesis capability exert protective effects against STZ-induced β cell death by activating autophagy in β cells.