HDAC1 overexpression enhances ß-cell proliferation by down-regulating Cdkn1b/p27.

The homeobox transcription factor Nkx6.1 is sufficient to increase functional ß-cell mass, where functional ß-cell mass refers to the combination of ß-cell proliferation, glucose-stimulated insulin secretion (GSIS) and ß-cell survival. Here, we demonstrate that the histone deacetylase 1 (HDAC1), which is an early target of Nkx6.1, is sufficient to increase functional ß-cell mass. We show that HDAC activity is necessary for Nkx6.1-mediated proliferation, and that HDAC1 is sufficient to increase ß-cell proliferation in primary rat islets and the INS-1 832/13 ß-cell line. The increase in HDAC1-mediated proliferation occurs while maintaining GSIS and increasing ß-cell survival in response to apoptotic stimuli. We demonstrate that HDAC1 overexpression results in decreased expression of the cell cycle inhibitor Cdkn1b/p27 which is essential for inhibiting the G1 to S phase transition of the cell cycle. This corresponds with increased expression of key cell cycle activators, such as Cyclin A2, Cyclin B1 and E2F1, which are activated by activation of the Cdk4/Cdk6/Cyclin D holoenzymes due to down-regulation of Cdkn1b/p27. Finally, we demonstrate that overexpression of Cdkn1b/p27 inhibits HDAC1-mediated ß-cell proliferation. Our data suggest that HDAC1 is critical for the Nkx6.1-mediated pathway that enhances functional ß-cell mass.

How Do Apps Work? An Analysis of Physical Activity App Users' Perceptions of Behavior Change Mechanisms.

BACKGROUND: Physical activity apps are commonly used to increase levels of activity and health status. To date, the focus of research has been to determine the potential of apps to influence behavior, to ascertain the efficacy of a limited number of apps to change behavior, and to identify the characteristics of apps that users prefer. OBJECTIVE: The purpose of this study was to identify the mechanisms by which the use of physical activity apps may influence the users' physical activity behavior. METHODS: This study used a cross-sectional survey of users of health-related physical activity apps during the past 6 months. An electronic survey was created in Qualtrics' Web-based survey software and deployed on Amazon Mechanical Turk. Individuals who had used at least one physical activity app in the past 6 months were eligible to respond. The final sample comprised 207 adults living in the United States. 86.0% (178/207) of respondents were between the ages of 26 and 54 years, with 51.2% (106/207) of respondents being female. Behavior change theory informed the creation of 20 survey items relating to the mechanisms of behavior change. Respondents also reported about engagement with the apps, app likeability, and physical activity behavior. RESULTS: Respondents reported that using a physical activity app in the past 6 months resulted in a change in their attitudes, beliefs, perceptions, and motivation. Engagement with the app (P<.001), frequency of app use (P=.03), and app price (P=.01) were related to the reported impact of the behavior change theory or mechanisms of change. The mechanisms of change were associated with self-reported physical activity behaviors (P<.001). CONCLUSIONS: The findings from this study provide an overview of the mechanisms by which apps may impact behavior. App developers may wish to incorporate these mechanisms in an effort to increase impact. Practitioners should consider the extent to which behavior change theory is integrated into a particular app when they consider making recommendations to others wishing to increase levels of physical activity.