Isoflavone glycosides: Synthesis and evaluation as α-glucosidase inhibitors

On the basis of the structure of 4′,7,8-trihydroxyisoflavone 7-O-α-D-arabinofuranoside (namely A-76202, 1), a Rhodococcus metabolite showing potent inhibitory activities against the α-glucosidases of rat liver microsome (IC 50 = 0.46 ng/mL), 26 analogs, each with minor variations at the sugar moiety and the isoflavone A and B rings, were readily synthesized. Notably, a new and efficient method was developed for the divergent synthesis of the B-ring congeners of the isoflavone glycosides by using Suzuki-Miyaura coupling as the final step. Modifications at the sugar moiety and the isoflavone A ring significantly diminish the activity, whereas variations at the B ring are largely tolerated for retaining the potent α-glucosidase inhibitory activity. © Wiley-VCH Verlag GmbH & Co. KGaA, 2008.postprin

The effect of pre-exercise galactose and glucose ingestion on high-intensity endurance cycling.

This study evaluated the effects of the pre-exercise (30 minutes) ingestion of galactose (Gal) or glucose (Glu) on endurance capacity as well as glycemic and insulinemic responses. Ten trained male cyclists completed 3 randomized high-intensity cycling endurance tests. Thirty minutes before each trial, cyclists ingested 1 L of either 40 g of glucose, 40 g of galactose, or a placebo in a double-blind manner. The protocol comprised 20 minutes of progressive incremental exercise (70-85% maximal power output [Wmax]); ten 90-second bouts at 90% Wmax, separated by 180 seconds at 55% Wmax; and 90% Wmax until exhaustion. Blood samples were drawn throughout the protocol. Times to exhaustion were longer with Gal (68.7 ± 10.2 minutes, p = 0.005) compared with Glu (58.5 ± 24.9 minutes), with neither being different to placebo (63.9 ± 16.2 minutes). Twenty-eight minutes after Glu consumption, plasma glucose and serum insulin concentrations were higher than with Gal and placebo (p < 0.001). After the initial 20 minutes of exercise, plasma glucose concentrations increased to a relative hyperglycemia during the Gal and placebo, compared with Glu condition. Higher plasma glucose concentrations during exercise, and the attenuated serum insulin response at rest, may explain the significantly longer times to exhaustion produced by Gal compared with Glu. However, neither carbohydrate treatment produced significantly longer times to exhaustion than placebo, suggesting that the pre-exercise ingestion of galactose and glucose alone is not sufficient to support this type of endurance performance

Absence of an acute insulin response predicts onset of type 2 diabetes in a Caucasian population with impaired glucose tolerance

Context: In persons with impaired glucose tolerance (IGT), both impaired insulin secretion and insulin resistance contribute to the conversion to type 2 diabetes mellitus (T2DM). However, few studies have used criterion standard measures to asses the predictive value of impaired insulin secretion and insulin resistance for the conversion to T2DM in a Caucasian IGT population. Objectives: The objective of the study was to determine the predictive value of measures of insulin secretion and insulin resistance derived from a hyperglycemic clamp, including the disposition index, for the development of T2DM in a Caucasian IGT population. Design, Setting, and Participants: The population-based Hoorn IGT study consisted of 101 Dutch IGT subjects (aged < 75 yr), with mean 2-h plasma glucose values, of two separate oral glucose tolerance tests, between 8.6 and 11.1 mmol/liter. A hyperglycemic clamp at baseline was performed to assess first-phase and second-phase insulin secretion and insulin sensitivity. During follow-up, conversion to T2DM was assessed by means of 6-monthly fasting glucose levels and yearly oral glucose tolerance tests. Results: The cumulative incidence of T2DM was 34.7%. Hazard ratio for T2DM development adjusted for age, sex, and body mass index was 5.74 [95% confidence interval (CI) 2.60-12.67] for absence of first insulin peak, 1.58 (95% CI 0.60-4.17) for lowest vs. highest tertile of insulin sensitivity, and 1.78 (95% CI 0.65-4.88) for lowest vs. highest tertile of the disposition index. Conclusions: In these Caucasian persons with IGT, the absence of the first insulin peak was the strongest predictor of T2DM. Copyright © 2008 by The Endocrine Society

Influence of 4-week intraduodenal supplementation of quercetin on performance, glucose metabolism, and mRNA abundance of genes related to glucose metabolism and antioxidative status in dairy cows

AbstractQuercetin has been shown to be a potent antioxidant, acts hepatoprotectively, and affects glucose and lipid metabolism in monogastrics. If this is also true in ruminants, quercetin could be beneficial in periparturient high-yielding dairy cows by ameliorating the negative effects of free radical formation and reducing the severity of liver lipidosis and ketosis. In a first attempt to evaluate effects of a long-term quercetin treatment, we intraduodenally administered twice daily 18mg of quercetin (Q)/kg of body weight to 5 late-lactation (215d in milk) dairy cows over a period of 28d. Frequent blood samples were taken before and during administration to determine plasma concentrations of flavonols and metabolites. Before and after 1 and 4wk of Q administration, glycogen and fat content as well as mRNA expression of selected genes were measured in liver biopsies. Furthermore, euglycemic, hyperinsulinemic, and hyperglycemic clamp studies were conducted before and after 2wk of Q administration. During the experiment, dry matter intake and most other zootechnical data remained unchanged. Milk protein content was increased in wk 2 and 4 of Q administration compared with basal values, whereas fat and lactose contents of milk remained unchanged. Plasma nonesterified fatty acids, γ-glutamyl transferase, cholesterol, glutamate dehydrogenase, triglyceride, and albumin concentrations, as well as liver fat and glycogen concentrations, were not affected by Q supplementation. Plasma glucose and β-hydroxybutyrate concentrations in plasma decreased and increased, respectively, under the influence of quercetin. During hyperglycemic clamp conditions, the relative increase of plasma insulin was higher after 2wk of Q administration, and a tendency for an increased rQUICKI (revised quantitative insulin sensitivity check index) was observed. The relative mRNA expression levels of selected genes related to glucose metabolism, fat metabolism, and antioxidative status were not altered after 1 or 4wk of Q supplementation. In conclusion, the effects on insulin release and sensitivity support the assumption that administration of Q could have positive effects on the metabolic adaption of high-yielding cows to early lactation. The increase of milk protein content in response to Q supplementation needs to be verified

Η Νομισματική Ένωση ως μορφή Ενισχυμένης Συνεργασίας στην Ευρωπαϊκή Ένωση

Αντικείμενο της παρούσας εργασίας αποτελεί η προσέγγιση των μηχανισμών της νομισματικής ένωσης και της ενισχυμένης εργασίας, ως δύο μηχανισμών ικανών να επιφέρουν διαφοροποιημένη ολοκλήρωση στους κόλπους της Ευρωπαϊκής Ένωσης, με σκοπό να εντοπιστούν οι ομοιότητες και οι διαφορές τους. Στο πρώτο μέρος της εργασίας παρουσιάζονται εκτενώς οι ευρεθείσες ομοιότητες των μηχανισμών, διακρίνοντας σε ομοιότητες που αφορούν αφενός το πεδίο εφαρμογής τους και αφετέρου το διαδικαστικό πλαίσιο λήψης αποφάσεων. Στο δεύτερο μέρος αντιστοίχως προσεγγίζονται οι ουσιώδεις διαφορές των μηχανισμών, οι οποίες αν και ολιγάριθμες, κρίνονται θεμελιώδεις και επαρκείς να αποτρέψουν τυχόν σύγχυση των υπό κρίση θεσμών. Η μεθοδολογία που χρησιμοποιήθηκε για την συγγραφή της εργασίας βασίζεται σε διμερές πλάνο, καθένα από τα μέρη της οποίας διαιρείται σε δύο κεφάλαια, τα οποία με την σειρά τους απαρτίζονται από δύο υποκεφάλαια. Σε πρώτο πάντα πεδίο εκτίθενται τα σχετικά με την νομισματική ένωση ευρήματα, ενώ σε δεύτερο ακολουθεί η προσέγγιση του μηχανισμού της ενισχυμένης συνεργασίας. Στην αφετηρία κάθε κεφαλαίου αναπτύσσεται εισαγωγική παράγραφος και κάθε κεφάλαιο φέρει το δικό του αυτοτελές συμπέρασμα. Από την μελέτη της εργασίας προκύπτει σαφώς το συμπέρασμα ότι οι υπό κρίση μηχανισμοί αν και φέρουν σημαντικές ομοιότητες τόσο στα ουσιαστικά όσο και στα διαδικαστικά χαρακτηριστικά τους, παραταύτα δεν δύνανται να ταυτιστούν, καθότι ελλοχεύουν μερικές πολυσήμαντες διαφοροποιήσεις στους μοχλούς ενεργοποίησής τους, αρκετές για να επιφέρουν αρνητικό αποτέλεσμα στην προσπάθεια εξομοίωσής τους.The subject of this dissertation is to touch upon the mechanisms of monetary union and enhanced cooperation, as mechanisms capable of bringing differentiated integration within the European Union in order that their similarities and differences will be identified. In the first part of this dissertation, the similarities of the mechanisms are outlined, distinguishing those between the scope and the procedural decision-making framework. The second part addresses the fundamental differences of the mechanisms, which are considered sufficient to prevent any confusion between the mechanisms in question. The methodology used for the drafting of the dissertation is based on a bilateral plan, consisting of two parts, as explained above, each of which is divided into two chapters, which are composed of two subchapters. In the first place, the findings on monetary union are outlined, followed by the development of enhanced co-operation. In the beginning of each chapter an introductory paragraph is developed and each chapter carries its own independent conclusion. Through the study of the dissertation it becomes evident that the mechanisms in question, although bearing significant similarities, can not be identified, since there are some variations of great value in their levers, which could have a negative effect on any assimilation effort

Stanniocalcin 1 effects on the renal gluconeogenesis pathway in rat and fish

The mammalian kidney contributes significantly to glucose homeostasis through gluconeogenesis. Considering that stanniocalcin 1 (STC1) regulates ATP production, is synthesized and acts in different cell types of the nephron, the present study hypothesized that STC1 may be implicated in the regulation of gluconeogenesis in the vertebrate kidney. Human STC1 strongly reduced gluconeogenesis from C-14-glutamine in rat renal medulla (MD) slices but not in renal cortex (CX), nor from C-14-lactic acid. Total PEPCK activity was markedly reduced by hSTC1 in MD but not in CX. Pck2 (mitochondrial PEPCK isoform) was down-regulated by hSTC1 in MD but not in CX. In fish (Dicentrarchus labrax) kidney slices, both STC1-A and -B isoforms decreased gluconeogenesis from C-14-acid lactic, while STC1-A increased gluconeogenesis from C-14-glutamine. Overall, our results demonstrate a role for STC1 in the control of glucose synthesis via renal gluconeogenesis in mammals and suggest that it may have a similar role in teleost fishes. (C) 2015 Elsevier Ireland Ltd. All rights reserved.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) Brazil; Foundation for Science and Technology of Portugal [PTDC/MAR/121279/2010]; bilateral programme CAPES (Brazil)/GRICES (Portugal) CAPES/GRICES [215/08]info:eu-repo/semantics/publishedVersio

Impulsiveness, postprandial blood glucose and glucoregulation affect measures of behavioral flexibility

Behavioral flexibility (BF) performance is influenced by both psychological and physiological factors. Recent evidence suggests that impulsivity and blood glucose can affect executive function, of which BF is a subdomain. Here, we hypothesized that impulsivity, fasting blood glucose (FBG), glucose changes (i.e. glucoregulation) from postprandial blood glucose (PBG) following the intake of a 15g glucose beverage could account for variability in BF performance. The Stroop Color-Word Test and the Wisconsin Card Sorting Test (WCST) were used as measures of BF, and the Barratt Impulsiveness Scale (BIS-11) to quantify participants’ impulsivity. In Study 1, neither impulsivity nor FBG could predict performance on the Stroop or the WCST. In Study 2, we tested whether blood glucose levels following the intake of a sugary drink, and absolute changes in glucose levels following the intake of the glucose beverage could better predict BF. Results showed that impulsivity and the difference in blood glucose between time 1 (postprandial) and time 2, but not blood glucose levels at time 2 per se could account for variation in performance on the WCST but not on the Stroop task. More specifically, lower impulsivity scores on the BIS-11, and smaller differences in blood glucose levels from time 1 to time 2 predicted a decrease in the number of total and perseverative errors on the WCST. Our results show that measures of impulsivity and glucoregulation can be used to predict BF. Importantly our data extend the work on glucose and cognition to a clinically relevant domain of cognition

The effect of pre-exercise galactose and glucose ingestion on high-intensity endurance cycling.

This study evaluated the effects of the pre-exercise (30 minutes) ingestion of galactose (Gal) or glucose (Glu) on endurance capacity as well as glycemic and insulinemic responses. Ten trained male cyclists completed 3 randomized high-intensity cycling endurance tests. Thirty minutes before each trial, cyclists ingested 1 L of either 40 g of glucose, 40 g of galactose, or a placebo in a double-blind manner. The protocol comprised 20 minutes of progressive incremental exercise (70-85% maximal power output [Wmax]); ten 90-second bouts at 90% Wmax, separated by 180 seconds at 55% Wmax; and 90% Wmax until exhaustion. Blood samples were drawn throughout the protocol. Times to exhaustion were longer with Gal (68.7 ± 10.2 minutes, p = 0.005) compared with Glu (58.5 ± 24.9 minutes), with neither being different to placebo (63.9 ± 16.2 minutes). Twenty-eight minutes after Glu consumption, plasma glucose and serum insulin concentrations were higher than with Gal and placebo (p < 0.001). After the initial 20 minutes of exercise, plasma glucose concentrations increased to a relative hyperglycemia during the Gal and placebo, compared with Glu condition. Higher plasma glucose concentrations during exercise, and the attenuated serum insulin response at rest, may explain the significantly longer times to exhaustion produced by Gal compared with Glu. However, neither carbohydrate treatment produced significantly longer times to exhaustion than placebo, suggesting that the pre-exercise ingestion of galactose and glucose alone is not sufficient to support this type of endurance performance