The molecular mechanisms underlying the
glucose-lowering effects of Isaria sinclairii (Cicada Dongchunghacho), a fungus cultured on silkworm, are not fully elucidated. Thus the
glucose-lowering effects of I. sinclairii as potential an
antidiabetic agent were investigated in C57BL/6 obese (ob/ob) mice over a 6-mo period. For a period of 26 wk, ob mice were administered either 5 or 10% (w/w) I. sinclairii
powder (IS), 10% dry mulberry leaf
powder (ML), or 10% silkworm (SW)
powder in the standard diet while a control group received only standard diet. The ML and SW preparations served as positive controls. Isaria sinclairii
at 10% in the diet was more effective in reducing
body weight compared to 10% ML, 10% SW, or 5% I. sinclairii. The fall in
blood glucose levels in the groups treated for 26 wk was greater in both IS groups at 1 mo compared to ML or SW but equal in all groups at 6 mo. Microarray analyses were performed with a mouse 7.4K
cDNA clone set array to identify the gene-expression profiles for the IS-, ML-, and SW-exposed ob mouse liver. The 10% IS group, compared to control, showed that 15 genes including
glucokinase (Gk-rs1) and
LDL receptor relating
protein 1 were upregulated and 12 genes including cell translocation gene2 (antiproliferative) and
hydroxyprostaglandin dehydrogenase (Hpgd 15) were downregulated. Upregulation of Gk-rs 1 and downregulation of Hpgd 15 were previously shown to occur in
drug-induced suppression of diabetes. With ML, Lepr (
leptin receptor), Pik3cb (phosphatidylinositol 3-kinase), and Prodh (
proline dehydrogenase), related to suppression of diabetes, were upregulated. In the case of SW, the
enzymes (G2an,
alpha glucosidase 2) and Mmp9 (
matrix metalloproteinase 9) involved in elevation of
blood glucose levels were both downregulated. Data suggest that I. sinclarii is effective in lowering
blood glucose due to the upregulation of
glucokinase (Gk-rs1) and downregulation of
hydroxyprostaglandin dehydrogenase (Hpgd 15), both associated with suppression of diabetes, indicating that microarray analysis is a useful tool to assess pharmacological potency of therapeutic compounds.