Inhibition of Insulin Secretion Induces Golgi Morphological Changes.

Objectives: The role of autophagy in pancreatic ß cells has been reported, but the relationship between autophagy and insulin metabolism is complex and is not fully understood yet. Design: We here analyze the relationship between autophagy and insulin metabolism from a morphological aspect. Methods: We observe the morphological changes of ß cell-specific Atg7-deficient mice and Atg5-deficient MIN6 cells with electron microscopy. Results: We find that Atg7-deficient ß cells exhibit a marked expansion of the endoplasmic reticulum (ER). We also find that the inhibitory state of insulin secretion causes morphological changes in the Golgi, including ministacking and swelling. The same morphological alterations are observed when insulin secretion is suppressed in Atg5-deficient MIN6 cells. Conclusions: The defect of autophagy induces ER expansion, and inhibition of insulin secretion induces Golgi swelling, probably via ER stress and Golgi stress, respectively.

An Overview of Golgi Membrane-Associated Degradation (GOMED) and Its Detection Methods.

Autophagy is a cellular mechanism that utilizes lysosomes to degrade its own components and is performed using Atg5 and other molecules originating from the endoplasmic reticulum membrane. On the other hand, we identified an alternative type of autophagy, namely, Golgi membrane-associated degradation (GOMED), which also utilizes lysosomes to degrade its own components, but does not use Atg5 originating from the Golgi membranes. The GOMED pathway involves Ulk1, Wipi3, Rab9, and other molecules, and plays crucial roles in a wide range of biological phenomena, such as the regulation of insulin secretion and neuronal maintenance. We here describe the overview of GOMED, methods to detect autophagy and GOMED, and to distinguish GOMED from autophagy.