Extracellular matrix stiffness mediates insulin secretion in pancreatic islets via mechanosensitive Piezo1 channel regulated Ca2+ dynamics.

The pancreatic islet is surrounded by ECM that provides both biochemical and mechanical cues to the islet ß-cell to regulate cell survival and insulin secretion. Changes in ECM composition and mechanical properties drive ß-cell dysfunction in many pancreatic diseases. While several studies have characterized changes in islet insulin secretion with changes in substrate stiffness, little is known about the mechanotransduction signaling driving altered islet function in response to mechanical cues. We hypothesized that increasing matrix stiffness will lead to insulin secretion dysfunction by opening the mechanosensitive ion channel Piezo1 and disrupting intracellular Ca2+ dynamics in mouse and human islets. To test our hypothesis, mouse and human cadaveric islets were encapsulated in a biomimetic reverse thermal gel (RTG) scaffold with tailorable stiffness that allows formation of islet focal adhesions with the scaffold and activation of Piezo1 in 3D. Our results indicate that increased scaffold stiffness causes insulin secretion dysfunction mediated by increases in Ca2+ influx and altered Ca2+ dynamics via opening of the mechanosensitive Piezo1 channel. Additionally, inhibition of Piezo1 rescued glucose-stimulated insulin secretion (GSIS) in islets in stiff scaffolds. Overall, our results emphasize the role mechanical properties of the islet microenvironment plays in regulating function. It also supports further investigation into the modulation of Piezo1 channel activity to restore islet function in diseases like type 2 diabetes (T2D) and pancreatic cancer where fibrosis of the peri-islet ECM leads to increased tissue stiffness and islet dysfunction.

Woman battering in Israel: the relative contributions of interpersonal factors.

Interpersonal factors were examined in 60 couples who reported violence by male against female partner and in 60 couples who did not. Violent men reported lower partnership quality and less social support than did nonviolent men. Battered women reported lower partnership quality but more positive social support than did women with nonviolent partners. Level of violence was predicted by level of child-rearing conflict and the availability of social support for the violent men.

PIP: This paper seeks to examine whether Israeli couples who report interpersonal violence would also report low-quality lives, conflict child-related interactions, and unsatisfactory social support outside the marriage. The sample included 60 violent men and their partners, matched with 60 nonviolent couples. Analyses were performed to determine differences between violent spouse and nonviolent spouse. Men's use of physical violence in relation to intimate and social relationships was also examined. Findings indicated that violent men and battered women tend to live with distinctly lower-quality marital relationships. Moreover, violent men had less social support than nonviolent men; whereas battered women had more positive social support than women with nonviolent partners did. Men's physical violence toward women was found to be associated with men's perception of high conflict over child rearing and the availability of close social support. Finally, the results of this study emphasize the importance of interpersonal relationship factors, both within and outside the marriage, when understanding relationships wherein men abuse their women partners.