Siraitia grosvenorii extract improves insulin tolerance and pancreatic islet function in ageing and HFD-induced diabetic mice

Siamenoside I (SI) is the sweetest compound isolated from Siraitia grosvenorii fruit. The extremely low natural abundance limits its application. We have previously produced an M3 extract (containing 68.5% SI) by subjecting Siraitia grosvenorii extract to a resin-immobilized snailase reaction, and obtained high-purity SI (96.4%) through a whole-cell biosynthetic approach. To investigate their effects, M3 extract was administered by gavage in ageing and high-fat diet (HFD)-fed diabetic C57BL/6J mice. The treatments improved glucose tolerance and insulin sensitivity, reduced liver steatosis, and upregulated hepatic glycogen storage and the expression of insulin signaling pathway components (insr, irs1, and irs2). In the pancreas from treated mice, the islets exhibited a preserved architecture, smaller size, and elevated expression of β-cell functional markers (pdx1, mafa, and glut2). In insulin-resistant HepG2 cells, high-purity SI treatment enhanced glucose uptake, glycogen synthesis, and the expression of insulin signaling pathway components. In conclusion, the biosynthesized products of M3 extract and high-purity SI improved insulin tolerance and pancreatic islet function, suggesting potential applications in healthcare products and anti-diabetic therapies.