Despite it is used as a nutraceutical against diabetes and obesity, the mechanism of action of bee pollen is still unclear. Pectic bee pollen polysaccharide (RBPP-P) was isolated from Rosa rugosa, and its structure was characterized by ¹³C-NMR and Fourier transform-infrared spectroscopy (FT-IR). Using high glucose and fatty acids-treated HepG2 cells and high fat diet (HFD)-induced obesity mice, we detected its effect on insulin function and lipid metabolism based on autophagy. RBPP-P contained arabinogalactan, rhamnogalacturonan I, and homogalacturonan domains. In vivo studies demonstrated that RBPP-P markedly ameliorated insulin resistance, glucose intolerance, and liver steatosis in obese mice. The suppressive effects of RBPP-P on liver steatosis and triglyceride content were mediated by increased autophagy and lipase expression in liver. In AMPK knockdown cells (prkaa 1/2^−/− MEF) and HFD-fed mice tissues (liver, gonadal white adipose, and inguinal white adipose), RBPP-P enhanced autophagy in AMPK/mTOR-dependent way in liver, but not in adipose tissue. These findings demonstrated that bee pollen polysaccharide alleviated liver steatosis and insulin resistance by promoting autophagy via an AMPK/mTOR-mediated signaling pathway, suggesting that RBPP-P could be a novel therapeutic agent used for the treatment of obesity and diabetes.

Insulin resistance is the main cause of type 2 diabetes, fatty liver and obesity. Our previous study found that mushroom polysaccharides improved insulin resistance in vitro, but the underlying mechanisms were still unknown. Thus, we investigate the hypoglycemic effects of polysaccharides from Gomphidiaceae rutilus fruiting bodies and their mechanisms. The total polysaccharides (AGRP) from Gomphidiaceae rutilus fruiting bodies and the neutral polysaccharide (AGRP-N) fraction both enhance insulin-stimulated glucose uptake in an autophagy-dependent manner in high glucose and fatty acid-treated hepatic cells, but not the acidic polysaccharide (AGRP-A) fraction. Further, we elucidate the oral hypoglycemic effects of polysaccharides on ob/ob mice. AGRP and AGRP-N lower blood glucose and improve insulin sensitivity. They inhibit liver lipid deposition, not only by activating AMPK to increase autophagy but also by increasing the expressions of PPARα and CPT-1a to enhance lipolysis. Our results provide a basis for the development of polysaccharides from Gomphidiaceae rutilus as a hypoglycemic healthy food.

Skeletal muscle insulin resistance is the main cause of type 2 diabetes, and mitochondria play a key role. Ginsenoside CK is the main active compound of ginseng with a variety of therapeutic effects, but few studies have reported on its mechanism towards skeletal muscle insulin resistance. Here, we found that CK significantly increased skeletal muscle insulin sensitivity, thereby alleviating hyperglycemia and insulin resistance. Furthermore, the effects of CK on skeletal muscle were associated with an improved mitochondrial fusion/fission dynamics balance and fatty acid oxidation. In fatty acid (FA)-induced C2C12 cells, CK promoted the translocation of GLUT4 to the cell membrane to improve glucose uptake and glycogen synthesis and also enhanced the mitochondrial quality. CK ameliorated the damaged mitochondrial membrane potential (ΔΨ_m), which was based on mitophagy activation. After the knockdown of mitophagy-related receptors, we found that DRP1/PINK1 was the key pathway of CK-induced mitophagy. These findings indicated that ginsenoside CK is a promising lead compound against diabetes.