chlorophyll-a and Diabetes-Mellitus--Type-2

This study investigated the molecular mechanisms underlying the antidiabetic effect of an ethanol extract of soy leaves (ESL) in db/db mice. Control groups (db/+ and db/db) were fed a normal diet (ND), whereas the db/db-ESL group was fed ND with 1% ESL for 8 weeks. Dietary ESL improved glucose tolerance and lowered plasma glucose, glycated hemoglobin, HOMA-IR, and triglyceride levels. The pancreatic insulin content of the db/db-ESL group was significantly greater than that of the db/db group. ESL supplementation altered pancreatic IRS1, IRS2, Pdx1, Ngn3, Pax4, Ins1, Ins2, and FoxO1 expression. Furthermore, ESL suppressed lipid accumulation and increased glucokinase activity in the liver. ESL primarily contained kaempferol glycosides and pheophorbides. Kaempferol, an aglycone of kaempferol glycosides, improved β-cell proliferation through IRS2-related FoxO1 signaling, whereas pheophorbide a, a product of chlorophyll breakdown, improved insulin secretion and β-cell proliferation through IRS1-related signaling with protein kinase A in MIN6 cells. ESL effectively regulates glucose homeostasis by enhancing IRS-mediated β-cell insulin signaling and suppressing SREBP-1-mediated hepatic lipid accumulation in db/db mice.

Topics: Animals; Chlorophyll; Diabetes Mellitus, Type 2; Glucose; Glycine max; Glycosides; Humans; Hypoglycemic Agents; Insulin; Insulin-Secreting Cells; Kaempferols; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Plant Extracts; Plant Leaves

Synthetic ligands of the retinoid X receptor (RXR) have shown antidiabetic activity in mice, apparently owing to the fact that they stimulate the transcriptional activity of PPAR-gamma/RXR heterodimers, much like thiazolidinedione drugs. The chlorophyll metabolite phytanic acid has been shown to be a natural ligand for RXR, active in concentrations near its physiological levels. It is thus reasonable to suspect that phytanic acid may have utility for treatment and prevention of human type 2 diabetes. Phytanic acid may mimic or complement various effects of conjugated linoleic acids, which have been shown to activate PPAR-gamma/RXR and prevent rodent diabetes. Administration of hydrolyzed chlorophyll may represent the most cost-effective strategy for raising human tissue levels of phytanic acid.

Topics: Animals; Chlorophyll; Diabetes Mellitus, Type 2; Humans; Linoleic Acid; Mice; Phytanic Acid; Receptors, Cytoplasmic and Nuclear; Transcription Factors