FIG. 2. Enhanced Nrf2 activity induces earlier onset of IR in Lep^ob/ob mice. Blood glucose concentration during glucose tolerance test (A) and insulin tolerance test (B) assay from 6-week-old mice (black squares, OB mice; gray squares, OBKeap1-KD mice; n = 5 to 6) is shown. C: Gene expression in SKM (n = 5 to 6). Immunoblot analysis of ser473-phospholylated-Akt (p-Akt), total-Akt (Akt) (D), and Glut4 (E) in SKM of 6-week-old mice is shown. $P < 0.05, Keap1-KD mice compared with WT mice; #P < 0.05, OB mice compared with WT mice; *P < 0.05, OBKeap1-KD mice compared with OB mice. Insr, insulin receptor; Irs, insulin receptor substrate; PGC, peroxisome proliferator–activated receptor γ coactivator; wk, weeks. FIG. 2. Enhanced Nrf2 activity induces earlier onset of IR in Lepob/ob mice. Blood glucose concentration during glucose tolerance test (A) and insulin tolerance test (B) assay from 6-week-old mice (black squares, OB mice; gray squares, OBKeap1-KD mice; n = 5 to 6) is shown. C: Gene expression in SKM (n = 5 to 6). Immunoblot analysis of ser473-phospholylated-Akt (p-Akt), total-Akt (Akt) (D), and Glut4 (E) in SKM of 6-week-old mice is shown. $P < 0.05, Keap1-KD mice compared with WT mice; #P < 0.05, OB mice compared with WT mice; *P < 0.05, OBKeap1-KD mice compared with OB mice. Insr, insulin receptor; Irs, insulin receptor substrate; PGC, peroxisome proliferator–activated receptor γ coactivator; wk, weeks. More

Figure 1 Overview of the role of the ATF/CREB family in the pathway involved in hepatic gluconeogenesis. The ATF/CREB family members play central roles in hepatic gluconeogenesis as transcriptional regulators. Under fasting conditions, elevated circulating glucagon binds G-protein–coupled receptor... More

FIG. 2. Central nervous system BDNF infusion fails to increase tissue glucose uptake in uncontrolled insulin-deficient diabetes. Tissue glucose uptake (Rg) determined from 2[¹⁴C]-deoxyglucose studies in tibialis anterior muscle (A) and BAT (B) and BAT expression of uncoupling protein-1 (Ucp1) (C) and peroxisome proliferator–activated receptor γ-coactivator-1 α (Pgc-1α) (D) in nondiabetic controls or in STZ-induced diabetic animals receiving intracerebroventricular vehicle and pair-fed or intracerebroventricular BDNF (n = 5–6 per group). Data represent mean ± SEM. *P < 0.05 vs. veh-veh. FIG. 2. Central nervous system BDNF infusion fails to increase tissue glucose uptake in uncontrolled insulin-deficient diabetes. Tissue glucose uptake (Rg) determined from 2[14C]-deoxyglucose studies in tibialis anterior muscle (A) and BAT (B) and BAT expression of uncoupling protein-1 (Ucp1) (C) and peroxisome proliferator–activated receptor γ-coactivator-1 α (Pgc-1α) (D) in nondiabetic controls or in STZ-induced diabetic animals receiving intracerebroventricular vehicle and pair-fed or intracerebroventricular BDNF (n = 5–6 per group). Data represent mean ± SEM. *P < 0.05 vs. veh-veh. More

FIG. 2. Effects of high glucose on glucose metabolism. A and B: Expression of glucose metabolic-related proteins. C: GCK immunocytochemistry. Results represent the average ± SE from three independent experiments (*P < 0.005, ** P < 0.05). D: Content of insulin and production of ATP. Results represent the average ± SE from three independent experiments (*P < 0.05, ** P < 0.01; n = 5). All data are representative of three independent experiments. HKI, hexokinase I; PGC-1, peroxisome proliferator–activated receptor γ coactivator 1; PI3K, phosphatidylinositol 3-kinase; SOD, superoxide dismutase; SREBP1, sterol regulatory element–binding protein 1. FIG. 2. Effects of high glucose on glucose metabolism. A and B: Expression of glucose metabolic-related proteins. C: GCK immunocytochemistry. Results represent the average ± SE from three independent experiments (*P < 0.005, ** P < 0.05). D: Content of insulin and production of ATP. Results represent the average ± SE from three independent experiments (*P < 0.05, ** P < 0.01; n = 5). All data are representative of three independent experiments. HKI, hexokinase I; PGC-1, peroxisome proliferator–activated receptor γ coactivator 1; PI3K, phosphatidylinositol 3-kinase; SOD, superoxide dismutase; SREBP1, sterol regulatory element–binding protein 1. More