isoquercitrin and Diabetes-Mellitus--Type-2

The aim was to investigate both individual and synergistic effects of quercetin-3-O-β-glucoside (Q3G) and fructooligosaccharide (FOS) on indices of metabolic syndrome and plasma total cholesterol level with potential mechanisms of action.. Five groups of rats were fed a dextrin-based diet as the normal reference group, or sucrose-based (S) diets with 0.3% Q3G, 5% FOS, or 0.3% Q3G + 5% FOS (Q3G + FOS) for 48 days. Oral glucose tolerance tests (OGTTs) were conducted on days 0, 14, 28, and 45, and adipose tissue and aortic blood were collected on day 48. Effects of Q3G and FOS on portal GLP-1 secretion were separately examined using rats after ileal administration.. Abdominal fat weight reduced in FOS-fed groups. Blood glucose levels of the Q3G + FOS group at 60 min in OGTT and HOMA-IR (0.25 ± 0.03 vs 0.83 ± 0.12 on day 45) were clearly lower in the Q3G + FOS group than in S group throughout the experimental period. Muscle Akt phosphorylation was enhanced only in the Q3G group. The plasma quercetin was largely increased by FOS feeding on day 48 (18.37 ± 1.20 with FOS, 2.02 ± 0.30 without FOS). Plasma total cholesterol levels in the Q3G + FOS group (3.10 ± 0.12, P < 0.05 on day 45) were clearly suppressed compared to the S group (4.03 ± 0.18). GLP-1 secretion was enhanced in Q3G + FOS group than in Q3G or FOS group.. Q3G + FOS diet improved glucose tolerance, insulin sensitivity, and total cholesterol level with increasing GLP-1 secretion and a higher level of blood quercetin. Q3G + FOS may reduce the risk of T2DM.

Topics: Absorption; Animals; Blood Glucose; Body Weight; Cecum; Cholesterol; Diabetes Mellitus, Type 2; Diet; Flavonoids; Fructose; Glucagon-Like Peptide 1; Glucose Tolerance Test; Hydrogen-Ion Concentration; Insulin Resistance; Male; Oligosaccharides; Phosphorylation; Proto-Oncogene Proteins c-akt; Quercetin; Rats; Rats, Wistar; Sucrose

This study conducted in vivo and in situ experiments with rats to investigate the glucagon-like peptide-1 (GLP-1) secretion in response to oral or ileal administration of α-glucosyl-isoquercitrin (20-40 mmol in 2 mL; Q3G), fructooligosaccharides (200 mmol in 2 mL; FOS) and Q3G + FOS. Direct effects on GLP-1-producing l-cells were also examined by an in vitro study using a murine enteroendocrine cell line, GLUTag. To evaluate the plasma GLP-1 level, blood samples from jugular cannula for in vivo and portal cannula for in situ experiments were obtained before and after administration of Q3G, FOS, or Q3G + FOS. We found tendencies for increases but transient stimulation of GLP-1 secretion by Q3G in in vivo and in situ experiments. Although FOS alone did not have any effects, Q3G + FOS enhanced and prolonged high plasma GLP-1 level in both experiments. In addition, application of Q3G on GLUTag cells stimulated GLP-1 secretion while FOS enhanced the effect of Q3G. Our results suggest that Q3G + FOS possess the potential for the management or prevention of Type 2 diabetes mellitus (T2DM) by enhancing and prolonging the GLP-1 secretion via direct stimulation of GLP-1 producing l-cell.

Topics: Animals; Cell Line; Diabetes Mellitus, Type 2; Enteroendocrine Cells; Glucagon-Like Peptide 1; Ileum; Male; Oligosaccharides; Quercetin; Rats; Rats, Wistar

The leaves of the white mulberry tree (Morus alba L.) are used worldwide in traditional medicine as anti-diabetics. Various constituents of mulberry leaves, such as iminosugars (i.e. 1-deoxynojirimicin), flavonoids and related compounds, polysaccharides, glycopeptides and ecdysteroids, have been reported to exert anti-diabetic activity, but knowledge about their contribution to the overall activity is limited. The objective of the present work was to determine the in vivo anti-diabetic activity of an extract of mulberry leaves (MA), and to examine to what extent three major constituents, chlorogenic acid, rutin and isoquercitrin, might contribute to the observed activity. Quantities of the three constituents of interest in the extract were determined by using HPLC-DAD. Activity was determined by using a type II diabetic rat model. After 11 days of per os administration of 250 or 750 mg/kg of MA or the corresponding amounts of each individual compound, a dose dependent decrease of non-fasting blood glucose levels were found for MA, chlorogenic acid and rutin, but not for isoquercitrin. Based on our results, chlorogenic acid and rutin might account for as much as half the observed anti-diabetic activity of MA, hence they can be considered as excellent markers for the quality control of mulberry products.

Topics: Administration, Oral; Animals; Biological Products; Blood Glucose; Chlorogenic Acid; Chromatography, High Pressure Liquid; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Morus; Phytotherapy; Plant Extracts; Plant Leaves; Quercetin; Rats; Rutin