Pterocarpan-Enriched Soy Leaf Extract Ameliorates Insulin Sensitivity and Pancreatic β-Cell Proliferation in Type 2 Diabetic Mice

Abstract

Abstract:In Korea, soy (Glycine max (L.) Merr.) leaves are eaten as a seasonal vegetable or pickled in soy sauce. Ethyl acetate extracts of soy leaves (EASL) are enriched in pterocarpans and have potent α-glucosidase inhibitory activity. This study investigated the molecular mechanisms underlying the anti-diabetic effect of EASL in C57BL/6J mice with high-fat diet (HFD)-induced type 2 diabetes. Mice were randomly divided into normal diet (ND), HFD (60 kcal% fat diet), EASL (HFD with 0.56% (wt/wt) EASL), and Pinitol (HFD with 0.15% (wt/wt) pinitol) groups. Weight gain and abdominal fat accumulation were significantly suppressed by EASL. Levels of plasma glucose, HbA1c, and insulin in the EASL group were significantly lower than those of the HFD group, and the pancreatic islet of the EASL group had greater size than those of the HFD group. EASL group OPEN ACCESSMolecules 2014, 19 18494 up-regulated neurogenin 3 (Ngn3), paired box 4 (Pax4), and v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA), which are markers of pancreatic cell development, as well as insulin receptor substrate 1 (IRS1), IRS2, and glucose transporter 4 (GLUT4), which are related to insulin sensitivity. Furthermore, EASL suppressed genes involved in hepatic gluconeogenesis and steatosis. These results suggest that EASL improves plasma glucose and insulin levels in mice with HDF-induced type 2 diabetes by regulating β-cell proliferation and insulin sensitivity.

Beneficial Effects of Pterocarpan-High Soybean Leaf Extract on Metabolic Syndrome in Overweight and Obese Korean Subjects: Randomized Controlled Trial

“…In this trial, the plasma TNF-α, IL-6 and PAI-1 levels were significantly decreased in the PT group after the 12 weeks of supplementation, although the interaction effect of time and group showed only the TNF-α level between the groups. In addition, a previous study showed that pterocarpan-enriched soy leaf supplementation led to inhibiting the gene expression of TNF-α and IL-6 in the white adipose tissue in type 2 diabetic mice [27]. Taken together, these observations indicate that the decreased TNF-α level may be induced by improving the plasma PAI-1 level.…”

“…In a previous study, PT ameliorated the insulin sensitivity and β-cell dysfunction in type 2 diabetic mice [27]. However, no clinical trial has been conducted to examine the anti-metabolic disorder effects with the transcriptome analysis in PT-supplemented subjects.…”

“…A pterocarpan-high soybean leaf extract (PT) was concentrated in vacuum and lyophilized to yield a dark brown powder (8.7 kg). The PT dissolved in methanol was filtered through a 0.45-μm poly (tetrafluoroethylene) filter (Whatman International, Ltd., Maidstone, UK) for HPLC analysis [27]. Coumestrol, which was obtained from Sigma-Aldrich (St. Louis, MO, USA), and phaseol, which was isolated from the PT [18], were used as external standards for HPLC analysis.…”

“…In addition, glyceollins (I–III), prenylated pterocarpan have known antiestrogenic effects in vivo [24,25]. In a previous study, soy leaf exhibited non-HDL-cholesterol lowering effects in hamsters [26]—as well as ethyl acetate extracts of soybean leaves, including pterocarpan—ameliorated the insulin sensitivity and improved the plasma glucose levels in high-fat diet (HFD)-induced type 2 diabetic mice [27]. We have also reported that the supplementation with soybean leaves (2 g/day) is beneficial for lowering the fasting blood glucose and plasma triglyceride levels in adult subjects with prediabetes [28], while another study found that soybean leaves supplementation (2 g/day) failed to promote weight-loss [29].…”

Photosynthesis and Kaempferol Yields of Soy Leaves Under ABA Application and Mechanical Wounding

“…Consumption of soy leaves or their extracts has been implicated in preventing type 2 diabetes, obesity, heart disease and cancer through a multitude of mechanisms such as enhancing pancreatic β-Cell function and suppressing hepatic lipid accumulation [1], downregulating adipogeneic transcription [3], inhibiting α-glucosidase [4], decreasing non-HDL to HDL cholesterol ratio [5], relaxing carotid arteries [6], inhibiting fatty acid synthase [7], cancer cell specific cytotoxicity [8], and reducing DNA damage [9]. Much of the bioactivity of soy leaves is thought to be linked to isoflavonoids, kaempferol glycosides and pterocarpans [10], which are absent or found in extremely low levels in soy seed [10,11]. Kaempferols' antioxidative, free radical scavenging and anti-inflammatory properties [12,13] also play a synergistic role in the aforementioned health benefits.…”