Moderate Hyperglycemia-Preventive Effect and Mechanism of Action of <i>Periplaneta americana</i> Oligosaccharides in Streptozotocin-Induced Diabetic Mice

Periplaneta americana is a kind of medicinal and edible insect, and its oligosaccharides (PAOS) have been reported to exert anti-inflammatory effects by regulating immunity, reducing oxidative stress, and meliorating gut microbiota. We hypothesized PAOS might benefit experimental diabetes mellitus (DM), an inflammatory disease coordinated by both innate and adaptive immunity. This study aimed to evaluate the effect of PAOS on glycemia and its potential mechanisms. Mice model of diabetes was established, and then the potential effects of PAOS was tested in vivo. Here, we found that PAOS triggered a moderate hyperglycemia-preventive effect on DM mice, showing markedly alleviated symptoms of DM, reduced blood glucose, and meliorated functions of liver and pancreas β cell. Deciphering the underlying mechanism of PAOS-improving diabetes, the results revealed that PAOS downregulated the blood glucose level by activating PI3K/AKT/mTOR and Keap/Nrf2/HO-1 pathways, meanwhile inhibiting TLR4/MAPK/NF-κB, Beclin1/LC3, and NLRP3/caspase1 pathways in vivo. Furthermore, analyses of the microbial community intriguingly exhibited that PAOS promoted the communities of bacteria producing short-chain fatty acids (SCFAs), whereas attenuating lipopolysaccharides (LPS)-producing ones that favored inflammatory tolerance. Collectively, balancing the intestinal bacterial communities by PAOS, which favored anabolism but suppressed inflammatory responses, contributed substantially to the glycemia improvement of PAOS in DM mice. Accordingly, PAOS might function as complementary and alternative medicine for DM