α-cell glucokinase suppresses glucose-regulated glucagon secretion

Glucagon secretion by pancreatic α-cells is triggered by hypoglycemia and suppressed by high glucose levels; impaired suppression of glucagon secretion is a hallmark of both type 1 and type 2 diabetes. Here, we show that α-cell glucokinase (Gck) plays a role in the control of glucagon secretion. Using mice with α-cell-specific inactivation of Gck (αGckKO mice), we find that glucokinase is required for the glucose-dependent increase in intracellular ATP/ADP ratio and the closure of K javax.xml.bind.JAXBElement@dee6e8 channels in α-cells and the suppression of glucagon secretion at euglycemic and hyperglycemic levels. αGckKO mice display hyperglucagonemia in the fed state, which is associated with increased hepatic gluconeogenic gene expression and hepatic glucose output capacity. In adult mice, fed hyperglucagonemia is further increased and glucose intolerance develops. Thus, glucokinase governs an α-cell metabolic pathway that suppresses secretion at or above normoglycemic levels; abnormal suppression of glucagon secretion deregulates hepatic glucose metabolism and, over time, induces a pre-diabetic phenotype

Mental Health and School Functioning for Girls in the Child Welfare System : the Mediating Role of Future Orientation and School Engagement

This study investigated the association between mental health problems and academic and behavioral school functioning for adolescent girls in the child welfare system and determined whether school engagement and future orientation meditated the relationship. Participants were 231 girls aged between 12 and 19 who had been involved with the child welfare system. Results indicated that 39% of girls reported depressive symptoms in the clinical range and 54% reported posttraumatic symptoms in the clinical range. The most common school functioning problems reported were failing a class (41%) and physical fights with other students (35%). Participants reported a mean number of 1.7 school functioning problems. Higher levels of depression and PTSD were significantly associated with more school functioning problems. School engagement fully mediated the relationship between depression and school functioning and between PTSD and school functioning, both models controlling for age, race, and placement stability. Future orientation was not significantly associated with school functioning problems at the bivariate level. Findings suggest that school engagement is a potentially modifiable target for interventions aiming to ameliorate the negative influence of mental health problems on school functioning for adolescent girls with histories of abuse or neglect