FIG. 3.

Molecular knockdown of DVC NR1 negated the glucose production–lowering effect of hypothalamic expression of AMPK-DN. A: Schematic representation of working hypothesis that molecular knockdown of the NR1 subunit of the NMDA receptor in the DVC negates the glucose production–lowering effect of MBH DN AMPK. B: Schematic representation of experimental design. MBH and DVC stereotaxic surgeries were performed on male Sprague-Dawley rats (∼240–280 g). Animals were injected with 3 μl/side of cannulae of adenovirus into the MBH (GFP or DN AMPK) and into the DVC (MM or shRNA-NR1) immediately postsurgery. After 1 week of recovery (day 7), vascular surgery (i.e., intravenous catherization) was performed. Rats were given 5 recovery days until clamp studies (day 11). Animals with simultaneous disruption of both MBH AMPK and DVC NR1 did not exhibit the expected increase in glucose infusion rate (C) or lowering in glucose production (D) of DN AMPK animals. □, basal glucose production; ■, clamp glucose production. E: Suppression of glucose production (GP) during the clamp period was expressed as percent decrease from basal glucose production. F: Glucose utilization was comparable in all groups. MBH GFP+ DVC MM (n = 5), MBH GFP + DVC NR1 (n = 5), MBH DN AMPK + DVC MM (n = 6), and MBH DN AMPK + DVC NR1 (n = 5). #P < 0.01.