To identify the roles for the cyclic AMP-dependent protein kinase (PKA) in the pancreatic β-cell a mouse model ( β-caPKA mice) was generated in which PKA activity can be induced specifically in the  β-cells upon tamoxifen administration.  β-caPKA mice were raised to 10 weeks of age before tamoxifen was administered, leading to enhanced acute insulin release in response to an intraperitoneal glucose tolerance test (IPGTT) with the 2 minute time-point being enhanced 3.6-fold and returning to baseline levels by 10 minutes. Acute insulin release (0-10 minutes) has been reported to be a major determinant of the efficacy of glucose clearance. This enhancement of acute insulin release in the  β-caPKA mice led to improved glucose tolerance, showing both lower and more rapid peak glucose ( β-caPKA mice = 172 mg/dl at 10 minutes; control mice = 257 mg/dl at 20 minutes).  β-caPKA mice also exhibited better ad libitum fed glucose, both in fasting/re-feeding and chronic (10-52 weeks of age) regimes, relative to littermate controls. However, hyperglycemic clamps also revealed that PKA activity can potentiate sustained phase insulin release. These experiments revealed no indication of hyperinsulinemia in the  β-caPKA mice, consistent with the improvement in glucose control being attributable to an improved profile of insulin secretion. To determine whether enhanced insulin release could improve glucose tolerance, 10 week old  β-caPKA and littermate controls were placed on a 45% high fat diet for 18 weeks, after which tamoxifen was administered to induced  β-cell PKA activity. 4 weeks after the induction of enhanced β-cell function in  β-caPKA mice, glucose intolerance (IPGTT) was fully reversed without differential effects upon  β-cell mass. These data show the capacity for regaining glucose control that lies in targeted enhancement of  β-cell function and emphasize the importance of acute phase insulin release in regaining glucose control.