Oral administration of human FGF21 expressed by mycelium of Cordyceps militaris improves blood glucose and lipid in type II diabetes mellitus.

ABSTRACT

The purpose of this study was to express human FGF21 (hFGF21) using Cordyceps militaris (C. militaris) as a bioreactor and to observe its hypoglycemic and lipid-lowering effects on type II diabetes. The recombinant plasmid pCB130-hFGF21 was transformed into C. militaris to form recombinant recombinant C. militaris (RhFGF21), the stability of RhFGF21 in vitro and in vivo was analyzed. RhFGF21 significantly promoted glucose uptake in a dose-dependent manner in adipocytes and increased the levels of p-PLCγ, p-FRS2 and p-ERK, which was consistent with the commercial hFGF21. In animal experiments, oral RhFGF21 obviously reduced the levels of glucose, insulin, TG, T-CHO, NEFA, and LDL-C in the blood, the contents of ALT, AST, TNF-α, MCP-1, F4/80, CD68 and CD11b in the fatty liver, and the apoptosis of pancreatic cells. C. militaris is an excellent carrier that can stabilize the expression of hFGF21 and protect the biological activity of hFGF21 during oral administration, which provides a theoretical basis for the development of hFGF21 oral preparations for type II diabetes.