Adiponectin is not required for exercise training-induced improvements in glucose and insulin tolerance in mice

Abstract

Adiponectin (Ad) is a potent insulin-sensitizing adipokine that has been found to activate pathways involved in the adaptation to exercise. Therefore, we examined whether Ad is required for the increased insulin response observed following exercise training in Ad knockout mice (AdKO). Eight weeks of exercise training significantly increased glucose and insulin tolerance in both wild type (WT) and AdKO mice. There were no differences in glucose tolerance between genotypes but insulin tolerance was improved to a greater extent in AdKO compared to WT mice following exercise training (+26%, P < 0.05). There were no genotype differences in the insulin-stimulated phosphorylation of AKT or AS160 in red or white gastrocnemius muscle (RG, WG). Exercise training increased total AKT and AS160 protein content in RG and total AS160 protein content in WG. There were no genotype differences in total AKT or AS160. However, exercise training induced a more robust increase in total AS160 in RG from AdKO (+44 ± 8%, P < 0.05) compared to WT mice (+28 ± 7%, P = 0.06). There were no differences in total GLUT4 or FAT/CD36 in RG or WG in WT or AdKO, with or without exercise training. Similarly, there were no differences in RER, VO2, or activity between any groups. Our results indicate the presence of Ad is not required for exercise-induced increases in insulin response. Furthermore, it appears that exercise may improve insulin sensitivity to a greater extent in the absence of Ad, suggesting the presence of an unknown compensatory mechanism.

Keywords: Adiponectin; adiponectin knockout mice; exercise training; glucose and insulin tolerance; insulin response; skeletal muscle.

Figure 1.

Blood glucose (A) and the area under the blood glucose curve (B) measured during an intraperitoneal glucose tolerance test. Data are expressed as mean ± SE, n = 10. Experimental groups not sharing a letter are significantly different, P < 0.05. WT‐Sed, wild‐type+no exercise; WT‐Ex, wild‐type+exercise training; AdKO‐Sed, Ad knockout+no exercise; Ad‐Ex, Ad knockout+exercise training.

Figure 2.

Blood glucose (A), the area over the entire blood glucose curve (B) and the area over the blood glucose curve strictly during the first 30 min measured during an intraperitoneal insulin tolerance test. Data are expressed as mean ± SE, n = 6. Experimental groups not sharing a letter are significantly different, P < 0.05. WT‐Sed, wild‐type+no exercise; WT‐Ex, wild‐type+exercise training; AdKO‐Sed, Ad knockout+no exercise; Ad‐Ex, Ad knockout+exercise training.

Figure 3.

Western blots of total AKT protein content (A) and basal (open bars) and insulin‐stimulated (filled bars) phosphorylation of AKT at threonine 308 (B) and serine 473 (C) from white gastrocnemius muscle. Data are expressed relative to basal WT‐Sed group, mean ± SE, n = 8–10. Experimental groups not sharing a letter are significantly different, P < 0.05. WT‐Sed, wild‐type+no exercise; WT‐Ex, wild‐type+exercise training; AdKO‐Sed, Ad knockout+no exercise; Ad‐Ex, Ad knockout+exercise training.

Figure 4.

Western blots of total AKT protein content (A) and basal (open bars) and insulin‐stimulated (filled bars) phosphorylation of AKT at threonine 308 (B) and serine 473 (C) from red gastrocnemius muscle. Data are expressed relative to basal WT‐Sed group, mean ± SE, n = 8–10. Experimental groups not sharing a letter are significantly different, P < 0.05. WT‐Sed, wild‐type+no exercise; WT‐Ex, wild‐type+exercise training; AdKO‐Sed, Ad knockout+no exercise; Ad‐Ex, Ad knockout+exercise training.

Figure 5.

Western blots of total AS160 protein content (A) and basal (open bars) and insulin‐stimulated (filled bars) phosphorylation of AKT at serine 318 (B) and serine 588 (C) from white gastrocnemius muscle. Data are expressed relative to basal WT‐Sed group, mean ± SE, n = 8–10. Experimental groups not sharing a letter are significantly different, P < 0.05. WT‐Sed, wild‐type+no exercise; WT‐Ex, wild‐type+exercise training; AdKO‐Sed, Ad knockout+no exercise; Ad‐Ex, Ad knockout+exercise training.

Figure 6.

Western blots of total AS160 protein content (A) and basal (open bars) and insulin‐stimulated (filled bars) phosphorylation of AKT at serine 318 (B) and serine 588 (C) from red gastrocnemius muscle. Data are expressed relative to basal WT‐Sed group, mean ± SE, n = 8–10. Experimental groups not sharing a letter are significantly different, P < 0.05. WT‐Sed, wild‐type+no exercise; WT‐Ex, wild‐type+exercise training; AdKO‐Sed, Ad knockout+no exercise; Ad‐Ex, Ad knockout+exercise training.

Figure 7.

Western blots of total GLUT4 (A, B) and FAT/CD36 (C, D) protein content from whole red (A, C) and white (B, D) gastrocnemius muscle. Data are expressed relative to WT‐Sed group, mean ± SE, n = 8–10. Experimental groups not sharing a letter are significantly different, P < 0.05. WT‐Sed, wild‐type+no exercise; WT‐Ex, wild‐type+exercise training; AdKO‐Sed, Ad knockout+no exercise; Ad‐Ex, Ad knockout+exercise training.