Cooperative effects of galanin and leptin on alleviation of insulin resistance in adipose tissue of diabetic rats

Abstract

It was reported that either orexigenic neuropeptide galanin or anorexigenic hormone leptin caught benefit insulin sensitivity through increasing the translocation of glucose transporter 4 (GLUT4) in patients with diabetes. To date, it is unknown whether galanin can potentiate the effect of leptin on alleviation of insulin resistance. Therefore, in the current study we sought to assess the combined effect of central leptin and galanin on insulin resistance in the adipose tissues of type 2 diabetic rats. Galanin and leptin were injected into the intracerebroventricle of the diabetic rats, respectively, or cooperatively once a day for 2 weeks. Then, several indexes of insulin resistance were examined. The results showed that glucose infusion rates in the hyperinsulinaemic-euglycaemic clamp test, plasma adiponectin content and GLUT4 translocation, as well as Akt phosphorylation in fat cells, were higher, not GLUT4 protein and GLUT4 mRNA expression, but HOMA index was lower in the galanin + leptin group than either one of them. Furthermore, treatment with MK-2206, an Akt inhibitor, blocked the combined effects of galanin + leptin on alleviation of insulin resistance. These results suggest that galanin can improve the leptin-induced mitigative effects on insulin resistance in the fat cells, and those provided new insights into the potential tactics for prevention and remedy of insulin resistance.

Keywords: Akt; GLUT4; adiponectin; diabetic models; insulin resistance.

FIGURE 1

The central effect of galanin and leptin on bodyweight and food intake of rats (n = 8). The bodyweight and food intake of animals were lower in the galanin + leptin group (DGL) or the galanin + MK‐2206 group (DGM) than the galanin group (DG), the both hormones + MK‐2206 group (DGLM) than DGL, and the leptin group (DL) than diabetic controls (DC). But both indexes were higher in DGL or the galanin + MK‐2206 group (DLM) than in DL, in DG than DC. The bodyweight was lower and food intake was higher in DC than the healthy controls (HC). Difference in the both indexes was non‐significant between DGLM and DGM, and between DGLM and DLM. The data are shown as the means ± SEM. ○P < .05, ○○P < .01 vs HC; ●P < .05 vs DC; △P < .05, △△P < .01 vs DG; □P < .05 vs DL; *P < .05 vs DGL

FIGURE 2

The effects of galanin and leptin on glucose infusing rates in hyperinsulinaemic‐euglycaemic clamp tests and glucose uptake in rats (n = 8). The glucose infusing rates and 2DG uptake were higher in the galanin + leptin group (DGL) than either galanin group (DG) or leptin group (DL), in DG or DL than diabetic controls (DC). However, the 2DG uptake and glucose infusing rates were lower in the both hormones + MK‐2206 group (DGLM) than DGL, in the galanin + MK‐2206 group (DGM) than DG, in DLM than DL and in DC than healthy controls (HC). Difference in both indexes was non‐significant between DGLM and DGM, and between DGLM and DLM. The data shown are the means ± SEM. ○○P < .01 vs HC; ●P < .05, ●●P < .01 vs DC; △P < .05, △△P < .01 vs DG; □P < .05, □□P < .01 vs DL; **P < .01 vs DGL

FIGURE 3

The central effect of galanin and leptin on GLUT4 trafficking to plasma membranes of fat cells (n = 8). The GLUT4 levels in plasma membranes were higher in the galanin + leptin group (DGL) than either galanin group (DG) or leptin group (DL), but not in total cell membranes (A). The ratios of the former to the latter were increased too (B). The GLUT4 levels in both membranes and their ratios were higher in DG or DL than diabetic controls (DC), but lower in the both hormones + MK‐2206 group (DGLM) than DGL, in the galanin + MK‐2206 group (DGM) than DG, in DLM than DL, and in DC than healthy controls (HC). Difference in the levels in both membranes and their ratio was non‐significant between DGLM and DGM, and between DGLM and DLM. The data shown are the means ± SEM. ○○P < .01 vs HC; ●P < .05, ●●P < .01 vs DC; △P < .05, △△P < .01 vs DG; □P < .05, □□P < .01 vs DL; *P < .05, **P < .01 vs DGL

FIGURE 4

The central effect of galanin and leptin on GLUT4 mRNA expression in adipose cells and plasma adiponectin levels in rats (n = 8). The plasma adiponectin levels were higher in the galanin + leptin group (DGL) than either galanin group (DG) or leptin group (DL), but GLUT4 mRNA expression in fat cells was almost changeless in DGL compared with DG and DL, respectively. Both indexes were higher in DG or DL than diabetic controls (DC), whereas that were lower in the both hormones + MK‐2206 group (DGLM) than DGL, in the galanin + MK‐2206 group (DGM) than DG, in DLM than DL and in DC than healthy controls (HC). Differences in the both indexes were non‐significant between DGLM and DGM, and between DGLM and DLM. The data shown are the means ± SEM. ○○P < .01 vs HC; ●P < .05, ●●P < .01 vs DC; △P < .05, △△P < .01 vs DG; □P < .05 vs DL; **P < .01 vs DGL

FIGURE 5

The central effect of galanin and leptin on pAkt and Akt levels and pAkt/Akt ratios in the fat cells of rats (n = 8). pAkt and Akt levels and their ratio were higher in the galanin + leptin group (DGL) than either galanin group (DG) or leptin group (DL), in DG or DL than diabetic controls (DC). However, the three indexes were lower in the both hormones + MK‐2206 group (DGLM) than DGL, in the galanin + MK‐2206 group (DGM) than DG, in DLM than DL and in DC than healthy controls (HC). Difference in the three indexes was non‐significant between DGLM and DGM, and between DGLM and DLM. The data shown are the means ± SEM. ○○P < .01 vs HC; ●P < .05, ●●P < .01 vs DC; △P < .05, △△P < .01 vs DG; □P < .05, □□P < .01 vs DL; **P < .01 vs DGL