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      Delphinidin 3‐rutinoside‐rich blackcurrant extract ameliorates glucose tolerance by increasing the release of glucagon‐like peptide‐1 secretion

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          Abstract

          Glucagon‐like peptide‐1 ( GLP‐1) is an incretin that is secreted from enteroendocrine L‐cells. Dietary factor‐stimulation of endogenous GLP‐1 is a promising strategy for increasing the action of GLP‐1. Recent studies have shown that berries rich in anthocyanins improve insulin sensitivity and reduce the risk of type 2 diabetes. Our previous study found that the anthocyanin delphinidin 3‐rutinoside (D3R) significantly increases GLP‐1 secretion in GLUTag cells (enteroendocrine L cell line). Blackcurrants are berries that contain high levels of anthocyanins, particularly D3R. Pre‐administered blackcurrant extract ( BCE) 5 mg/kg body weight (1 mg D3R/kg) significantly ameliorated glucose tolerance after intraperitoneal glucose injection in rats by stimulating the secretion of GLP‐1 and subsequently inducing insulin secretion. D3R did not break down significantly in the gastrointestinal tract for at least 45−60 min after BCE was administered, suggesting that BCE‐induced GLP‐1 secretion is mainly mediated by D3R and not its degradation products. These findings demonstrate the novel biological function of D3R‐rich BCE as a GLP‐1 secretagogue. An increase in endogenous GLP‐1 secretion induced by BCE may help to reduce the dosages of diabetic medicines and prevent diabetes.

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          Most cited references14

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          Glucagon-like peptide-1 7-36: a physiological incretin in man.

          The physiological role of glucagon-like peptide-1 7-36 amide (GLP-1 7-36) in man was investigated. GLP-1 7-36-like immunoreactivity was found in the human bowel; its circulating level rose after oral glucose and after a test breakfast. When it was infused into seven volunteers at a rate to mimic its postprandial plasma concentration in the fasting state, plasma insulin levels rose significantly and glucose and glucagon concentrations fell. During an intravenous glucose load, it greatly enhanced insulin release and significantly reduced peak plasma glucose concentrations, compared with a control saline infusion, even inducing postinfusion reactive hypoglycaemia. By comparison, infusion of glucose-dependent insulinotropic peptide (GIP) to physiological levels was less effective in stimulating insulin release. These observations suggest that GLP-1 7-36 is a physiological incretin and that it is more powerful than GIP. The observation of greatly increased postprandial plasma GLP-1 7-36 levels in patients with postgastrectomy dumping syndrome suggests that it may mediate the hyperinsulinaemia and reactive hypoglycaemia of this disorder.
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            Bioactives in blueberries improve insulin sensitivity in obese, insulin-resistant men and women.

            Dietary supplementation with whole blueberries in a preclinical study resulted in a reduction in glucose concentrations over time. We sought to evaluate the effect of daily dietary supplementation with bioactives from blueberries on whole-body insulin sensitivity in men and women. A double-blinded, randomized, and placebo-controlled clinical study design was used. After screening to resolve study eligibility, baseline (wk 0) insulin sensitivity was measured on 32 obese, nondiabetic, and insulin-resistant subjects using a high-dose hyperinsulinemic-euglycemic clamp (insulin infusion of 120 mU(861 pmol)⋅m(-2)⋅min(-1)). Serum inflammatory biomarkers and adiposity were measured at baseline. At the end of the study, insulin sensitivity, inflammatory biomarkers, and adiposity were reassessed. Participants were randomized to consume either a smoothie containing 22.5 g blueberry bioactives (blueberry group, n = 15) or a smoothie of equal nutritional value without added blueberry bioactives (placebo group, n = 17) twice daily for 6 wk. Both groups were instructed to maintain their body weight by reducing ad libitum intake by an amount equal to the energy intake of the smoothies. Participants' body weights were evaluated weekly and 3-d food records were collected at baseline, the middle, and end of the study. The mean change in insulin sensitivity improved more in the blueberry group (1.7 ± 0.5 mg⋅kg FFM(-1)⋅min(-1)) than in the placebo group (0.4 ± 0.4 mg⋅kg FFM(-1)⋅min(-1)) (P = 0.04). Insulin sensitivity was enhanced in the blueberry group at the end of the study without significant changes in adiposity, energy intake, and inflammatory biomarkers. In conclusion, daily dietary supplementation with bioactives from whole blueberries improved insulin sensitivity in obese, nondiabetic, and insulin-resistant participants.
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              Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels after an oral glucose tolerance test in patients with type 2 diabetes.

              In response to a meal, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are released and modulate glycemic control. Normally these incretins are rapidly degraded by dipeptidyl peptidase-4 (DPP-4). DPP-4 inhibitors are a novel class of oral antihyperglycemic agents in development for the treatment of type 2 diabetes. The degree of DPP-4 inhibition and the level of active incretin augmentation required for glucose lowering efficacy after an oral glucose tolerance test (OGTT) were evaluated. The objective of the study was to examine the pharmacodynamics, pharmacokinetics, and tolerability of sitagliptin. This was a randomized, double-blind, placebo-controlled, three-period, single-dose crossover study. The study was conducted at six investigational sites. The study population consisted of 58 patients with type 2 diabetes who were not on antihyperglycemic agents. Interventions included sitagliptin 25 mg, sitagliptin 200 mg, or placebo. Measurements included plasma DPP-4 activity; post-OGTT glucose excursion; active and total incretin GIP levels; insulin, C-peptide, and glucagon concentrations; and sitagliptin pharmacokinetics. Sitagliptin dose-dependently inhibited plasma DPP-4 activity over 24 h, enhanced active GLP-1 and GIP levels, increased insulin/C-peptide, decreased glucagon, and reduced glycemic excursion after OGTTs administered at 2 and 24 h after single oral 25- or 200-mg doses of sitagliptin. Sitagliptin was generally well tolerated, with no hypoglycemic events. In this study in patients with type 2 diabetes, near maximal glucose-lowering efficacy of sitagliptin after single oral doses was associated with inhibition of plasma DPP-4 activity of 80% or greater, corresponding to a plasma sitagliptin concentration of 100 nm or greater, and an augmentation of active GLP-1 and GIP levels of 2-fold or higher after an OGTT.
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                Author and article information

                Contributors
                tsudat@isc.chubu.ac.jp
                Journal
                Food Sci Nutr
                Food Sci Nutr
                10.1002/(ISSN)2048-7177
                FSN3
                Food Science & Nutrition
                John Wiley and Sons Inc. (Hoboken )
                2048-7177
                07 April 2017
                July 2017
                : 5
                : 4 ( doiID: 10.1002/fsn3.2017.5.issue-4 )
                : 929-933
                Affiliations
                [ 1 ] College of Bioscience and Biotechnology Chubu University Kasugai Aichi Japan
                Author notes
                [*] [* ] Correspondence

                Takanori Tsuda, College of Bioscience and Biotechnology, Chubu University, Matsumoto‐cho, Kasugai, Aichi 487‐8501, Japan.

                Email: tsudat@ 123456isc.chubu.ac.jp

                Author information
                http://orcid.org/0000-0002-7761-8824
                Article
                FSN3478
                10.1002/fsn3.478
                5520870
                449d4691-298f-4893-9255-847713e2d338
                © 2017 The Authors. Food Science & Nutrition published by Wiley Periodicals, Inc.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 August 2016
                : 02 February 2017
                : 21 February 2017
                Page count
                Figures: 2, Tables: 2, Pages: 5, Words: 3525
                Funding
                Funded by: Japan Society for Promotion of Science
                Award ID: 26450168
                Categories
                Original Research
                Original Research
                Custom metadata
                2.0
                fsn3478
                July 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.1.4 mode:remove_FC converted:21.07.2017

                anthocyanin,blackcurrant extract,delphinidin 3‐rutinoside,diabetes,glucagon‐like peptide‐1

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