Kyoto, Japan -- A hallmark of Type 2 diabetes is the progressive loss of beta cell mass: cells in the pancreas that produce and release insulin.  The endoplasmic reticulum stress response, a cellular pathway that maintains protein homeostasis, plays a critical role in beta cell function and survival, and the protein ATF6α is one of the key regulators of this stress response. However, the significance of ATF6α signaling in the stress-adaptive regulation of beta cell mass has remained unclear, prompting a team of researchers at Kyoto University to investigate.

"Our previous single-cell RNA-sequencing data suggested transient ATF6α upregulation during adaptive beta-cell proliferation, which sparked our interest in its potential role," says first author Daisuke Otani.

The team generated mice lacking ATF6α, specifically in beta cells. They assessed beta cell mass, proliferation and apoptosis, or cell death, of the mice under chronic stress conditions, including high-fat diet and pregnancy. The team also performed complementary in vitro experiments using chronically stressed beta cell lines, and single-cell RNA sequencing using the high-fat diet model.

Kyoto, Japan -- Our childhood experiences create ripple effects across our lives and with those whom we encounter. Adverse childhood experiences, or ACEs, have been linked to depression and dementia, and even to perpetuating abuse. The intergenerational transmission of abuse is well- known to affect the children of victims, and recent evidence has also connected a high number of ACEs to an increased risk of abusing elders, indicating broad impacts on later-life relationships and violent behavior.

However, attention is also turning to positive childhood experiences -- PCEs -- which include supportive family relationships, school belonging, and community support. Previous research suggests more PCEs are associated with lower stress and depression along with better health in adulthood. However, their association with the perpetration of elder abuse and cumulative ACE exposure has not yet been explored. A team of researchers at Kyoto University resolved to investigate the association between these opposing factors.

"By distinguishing family and community-related PCEs, we aimed to capture childhood influences on elder abuse from multiple perspectives," says first author Chie Koga.