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

Siamenoside I (SI) is the sweetest compound isolated from <i>Siraitia grosvenorii</i> fruit. The extremely low natural abundance limits its application. We have previously produced an M3 extract (containing 68.5% SI) by subjecting <i>Siraitia grosvenorii</i> 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 (<i>insr</i>, <i>irs1</i>, and <i>irs2</i>). In the pancreas from treated mice, the islets exhibited a preserved architecture, smaller size, and elevated expression of β-cell functional markers (<i>pdx1</i>, <i>mafa</i>, and <i>glut2</i>). 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.