Silk protein is an important natural resource for the preparation of silk-based hydrogels. Its remarkable mechanical properties and biological characteristics give it an important position in the field of biomedicine.

Flavonoid compounds such as luteolin exhibit hypolipidemic effects, and there are few reports on the hypoglycemic activity of luteolin derivatives. In this research, 6,8-(1,3-diaminoguanidine) luteolin (DAGL) and its Cr complex (DAGL·Cr) were obtained as a result of structural modifications to luteolin, and the hypoglycemic activities and the composition of intestinal microbiota in T2DM mice were investigated. This study found that DAGL and DAGL·Cr could significantly restore body weight, FBG, OGTT, AUC, and GSP in T2DM mice. Moreover, the pancreatic islet function index and the biochemical indicators of serum and the liver were also significantly improved. The histopathological results also showed that DAGL and DAGL·Cr had a stronger repair ability in the liver and the pancreas. It was also revealed that the potential hypoglycemic mechanism of DAGL and DAGL·Cr was involved in the simultaneous regulation of PI3K/AKT-1/GSK-3β/GLUT-4 and PI3K/AKT-1/mTOR/S6K1/IRS-1. Furthermore, DAGL and DAGL·Cr could also regulate the structure of the intestinal microbiota and increase the content of SCFA to relieve the symptoms of hyperglycemia in T2DM mice. This included a significant reduction in the ratio of Firmicutes and Bacteroidetes (F/B), and at the genus level, an increase in the relative abundance of Alistipe and Ruminiclostridium, and improvement in the content of SCFA in the feces of T2DM mice. In conclusion, in this study, DAGL and DAGL·Cr were found to improve hyperglycemia in T2DM mice by improving the pancreatic islet function index, regulating the biochemical indicators of serum and the liver, repairing damaged tissues, and regulating the PI3K/AKT-1 signaling pathway as well as reducing F/B, increasing the relative abundance of intestinal beneficial microbiota, and the content of SCFA in the feces. The hypoglycemic effect of DAGL·Cr on the body weight, serum IL-10, serum IL-6, and pancreatic islet function index was significantly better than that of DAGL.

Type 2 diabetes mellitus (T2DM) is typically accompanied by sudden weight loss, dyslipidemia-related indicators, decreased insulin sensitivity, and altered gut microbial communities. Fagopyrum tataricum possesses many biological activities, such as antioxidant, hypolipidemic, and hypotensive activities. However, only a few studies have attempted to elucidate the regulatory effects of F. tataricum ethanol extract (FTE) on intestinal microbial communities and its potential relationships with T2DM. In this study, we established a T2DM mouse model and investigated the regulatory effects of FTE on hyperglycemia symptoms and intestinal microbial communities. FTE intervention significantly improved the levels of fasting blood glucose, the area under the curve of oral glucose tolerance test (OGTT), and glycosylated serum protein, as well as pancreas islet function correlation index. In addition, FTE effectively improved hepatic and cecum injuries and insulin secretion due to T2DM. It was also revealed that the potential hypoglycemic mechanism of FTE was involved in the regulation of protein kinase B (AKT-1) and glucose transporter 2 (GLUT-2). Furthermore, compared with the Model group, the FTE-H intervention exhibited a significantly decreased ratio of Firmicutes to Bacteroidetes at the phylum level, reduced relative abundance of pernicious bacteria at the genus level, such as Desulfovibrio, Oscillibacter, Blautia, Parabacteroides, and Erysipelatoclostridium, and ameliorated inflammatory response and insulin resistance. Moreover, the correlation between gut microbiota and hypoglycemic indicators was predicted. The results showed that Lachnoclostridium, Lactobacillus, Oscillibacter, Bilophila, and Roseburia have the potential to be used as bacterial markers for T2DM. In conclusion, our research showed that FTE alleviates hyperglycemia symptoms by regulating the expression of AKT-1 and GLUT-2, as well as intestinal microbial communities in T2DM mice.

Luteolin (LUT), a natural flavonoid known for its hypoglycemic properties, is primarily sourced from vegetables such as celery and broccoli. However, its poor stability and low bioavailability in the upper digestive tract hinder its application in the functional food industry. To address these challenges, this study employed porous starch (PS) as a carrier to develop PS microspheres loaded with luteolin (PSLUT), simulating its release in vitro. The research assessed the hypoglycemic effects of LUT in type 2 diabetes mellitus (T2DM) mice both before and after PS treatment. In vitro findings demonstrated that PS improved LUT's stability in simulated gastric fluids and enhanced its in vivo bioavailability, aligning with experimental outcomes. PSLUT administration significantly improved body weight, fasting blood glucose (FBG), oral glucose tolerance test (OGTT), pancreatic islet function, and other relevant indicators in T2DM mice. Moreover, PSLUT alleviated abnormal liver biochemical indicators and liver tissue injury caused by T2DM. The underlying hypoglycemic mechanism of PSLUT is thought to involve the regulation of protein kinase B (AKT-1) and glucose transporter 2 (GLUT-2). After four weeks of intervention, various PSLUT doses significantly reduced the Firmicutes to Bacteroidetes ratio at the phylum level and decreased the relative abundance of harmful bacteria at the genus level, including Acetatifactor, Candidatus-Arthromitus, and Turicibacter. This microbial shift was associated with improvements in hyperglycemia-related indicators such as FBG, the area under the curve (AUC) of OGTT, and homeostasis model assessment of insulin resistance (HOMA-IR), which are closely linked to these bacterial genera. Additionally, Lachnoclostridium, Parasutterella, Turicibacter, and Papillibacter were identified as key intestinal marker genera involved in T2DM progression through Spearman correlation analysis. In conclusion, PS enhanced LUT's hypoglycemic efficacy by modulating the transcription and protein expression levels of AKT-1 and GLUT-2, as well as the relative abundance of potential gut pathogens in T2DM mice. These results provide a theoretical foundation for advancing luteolin's application in the functional food industry and further investigating its hypoglycemic potential.

Onchidium struma polysaccharides (OsPs) are natural biologically active compounds, and our previous work showed that they can inhibit the activity of α-glucosidase in vitro, showing potential hypoglycemic activity. However, the effects of OsPs on type 2 diabetes mellitus (T2DM) in vivo remain unknown. Thus, the anti-diabetic activity of OsPs was evaluated in the present study in diabetic mice. The results showed that OsPs can significantly ameliorate the features of T2DM in mice by improving the levels of fasting blood glucose (FBG), oral glucose tolerance test (OGTT), and pro-inflammatory factors, and ameliorating insulin resistance. Furthermore, OsPs can significantly improve biochemical indicators, decrease the contents of total cholesterol (TC) and triglyceride (TG), and reduce lipid accumulation in the liver. The possible mechanism of the prevention and treatment of T2DM by OsPs may involve the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT-1) signaling pathway. OsPs can regulate the dysbiosis of gut microbiota and reverse the abundance of Lactobacillus in mice with T2DM. Moreover, OsPs significantly increased the concentration of short-chain fatty acids (SCFAs) in mice with T2DM. Our results indicate that OsPs can be used as a novel food supplement for the prevention and treatment of T2DM.

Type 2 diabetes mellitus (T2DM) is an endocrine–metabolic disorder characterized by pancreatic islet dysfunction-induced hyperglycemia, which triggers hepatic injury, intestinal microbiota dysbiosis, and systemic complications. Fagopyrum tararicum seeds exhibit various biological activities, including antioxidant, hypolipidemic, and antihypertensive effects. However, there is limited research exploring how supernatants derived from the water extraction–ethanol precipitation of Fagopyrum tararicum seeds (SWEPFT) modulate the intestinal microbiota and their potential link to T2DM. This study evaluates SWEPFT’s effects on hyperglycemia and intestinal microbiota in T2DM mice. After a 4-week therapeutic period, SWEPFT markedly ameliorated hyperglycemia, as evidenced by reduced body weight (BW), fasting blood glucose (FBG), and glycated serum protein (GSP) and improved insulin sensitivity/resistance indicators (HOMA-IS/IR) and β-cell function (HOMA-β). Furthermore, the levels of both Akt1 and Slc2a2 transcription displayed notable enhancement. SWEPFT-H (high-dose SWEPFT) exhibited superior effects to SWEPFT-L (low-dose SWEPFT) in improving BW, FBG, and HOMA-IS. Moreover, SWEPFT modulated the intestinal microbiota by decreasing the Firmicutes/Bacteroidetes ratio, augmenting the proportion of Intestinimonas and Ruminiclostridium, and increasing the short-chain fatty acid content. A correlation analysis identified Candidatus_Arthromitus, Anaeroplasma, Candidatus_Stoquefichus, and Harryflintia as potential T2DM biomarkers linked to glycemic regulation. These findings elucidate SWEPFT’s critical role in microbiota modulation and hyperglycemia alleviation, providing a novel perspective for T2DM pathogenesis research and therapeutic development.