Recycling of glucagon receptor to plasma membrane increases in adipocytes of obese rats by soy protein; implications for glucagon resistance

SCOPE: Hyperglucagonemia contributes to hyperglycemia in type 2 diabetes (T2D). Previously, we have found that soy protein normalized fasting hyperglucagonemia in obese Zucker (fa/fa) rats, sensitizing the HSL‐lipolytic signaling pathway in white adipose tissue (WAT), however the mechanism remains unknown. METHODS AND RESULTS: Zucker (fa/fa) rats were fed casein or soy protein diet in combination with soybean or coconut oil. Glucagon receptor (GR) was increased at the plasma membrane of adipocytes of rats fed soy protein compared to those fed casein, without changes in total GR abundance. The protein abundance of Rab4, a GTPase involved in GR fast recycling, was dramatically up‐regulated in adipocytes of rats fed soy protein. The proportion of GR bound to Rab4 or to RAMP2, involved in promoting GR ligand‐binding and G protein selectivity, increased when soy protein was combined with soybean oil as fat source. In rats fed soy protein with coconut oil, Rab11 levels, a protein involved in the slow recycling of GR, was also increased. CONCLUSION: Soy protein increases GR recycling to the membrane of adipocytes and its ligand‐binding and G protein selectivity, suggesting, it could be used in T2D dietary treatment to reestablish glucagon sensitivity in WAT, leading to the regulation of circulating glucagon levels.