Abstract
Glyceollins are known to anti‐estrogenic phytoalexins but they have not been studied for anti‐diabetic properties. We hypothesized that glyceollins play an important role in glucose homeostasis through regulating glucose utilization in adipocytes and by improving ¥â‐cell function and survival in vitro and in vivo. Glyceollins improved insulin‐stimulated glucose uptake in 3T3‐L1 adipocytes without activating the peroxisome proliferator‐activated receptor‐gamma‐¥ã agonist. In addition, glyceollins slightly improved glucose‐stimulated insulin secretion without palmitate treatment in Min6 cells, and they potentiated insulinotropic actions when 500¥ìM palmitate treatment was used to induce ¥â‐cell dysfunction. This was associated with decreased ¥â‐cell apoptosis due to attenuation of ER stress, determined by mRNA levels of XBP‐1, ATF4, ATF6 and CHOP. The 8‐week oral consumption of the fraction containing glyceollins improved glucose tolerance during oral glucose tolerance test in diabetic mice induced by low‐dose multiple injections of streptozotocin. It also potentiated glucose‐stimulated insulin secretion and prevented ¥â‐cell apoptosis in the mice. In conclusion, glyceollins help normalize glucose homeostasis by potentiating ¥â‐cell function and survival and by improving glucose utilization in adipocytes.
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