Alternative to Sugar, Honey Does Not Provoke Insulin Resistance in Rats Based on Lipid Profiles, Inflammation, and IRS/PI3K/AKT Signaling Pathways Modulation

Insulin resistance (IR) is the central link to metabolic syndrome (MS), and IR prevention has become the key to overcoming this worldwide public health problem. A diet rich in simple sugars is an important pathogenic factor in IR development. To investigate the effect of honey on IR compared to the sugar-water diet, we analyzed phenolics and oligosaccharides in jujube honey and rape honey based on LC-MS and silane derivatization/GC-MS. The effects of different diets on glucose and lipid profile, histopathology and IR-related mechanism pathways were analyzed and compared by equal sugar levels intervention of fructose, fructose + glucose and two kinds of unifloral honey (high-/low-dose) in rats. The results suggested that sugar-equivalent honey, which differs from sugar solution, especially 17.1 g/kg BW jujube honey rich in phenolics (1.971 mg/100 g of isoquercitrin) and oligosaccharides (2.18 g/100 g of turanose), suppressed IR via maintaining glucose (OGTT and ITT) and lipid (TC, TG, LDL-C, HDL-C, and NEFA) homeostasis, improving histological structural abnormalities of the liver, adipose and skeletal muscle, reducing oxidative stress (GSH-Px and MDA) and inflammation (IL-6 and TNF-α), modulating the NF-κB (NF-κB gene expression was down-regulated to 0.94) and IRS/PI3K/AKT signaling pathways (e.g., AKT and GLUT2 expression in liver increased by 4.56 and 13.37 times, respectively) as well as reshaping the gut microbiota. These revealed a potential nutritional contribution of substituting honey for simple sugar in the diet, providing a theoretical basis for controlling IR development via dietary modification and supplementation.