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Home , Isomaltulose, Metabolism

e38 Care Volume 39, March 2016

Effects of Palatinose and Intake Farnaz Keyhani-Nejad,1,2 Margrit Kemper,1,2,3 Rita Schueler,1 on and Olga Pivovarova,1,2 Natalia Rudovich,1,2 and Secretion in Subjects With Type 2 1,2,3 Diabetes Andreas F.H. Pfeiffer Diabetes Care 2016;39:e38–e39 | DOI: 10.2337/dc15-1891

Excessive intake is associated with Millipore Corp., Billerica, MA). and then rapidly declined to nearly higher risk of insulin resistance and and glucagon were baseline values within 60 min postload. (T2D) (1). Recently, we assessed by ELISA kits (Mercodia, Uppsala, Conversely, GLP-1 concentrations after reported that Palatinose (isomaltulose), a Sweden). Palatinose ingestion decreased slightly 1,6-linked glucose- dimer that In comparison with sucrose intake, but remained significantly higher is completely digested and absorbed in peak glucose concentrations were sig- than sucrose. Accordingly, GLP-1iAUC the small intestine (2), improved glu- nificantly 2.5 mmol/L (20%) lower with was remarkably and significantly 6.3-fold cose and prevented fatty Palatinose ingestion (P , 0.01) (Fig. 1A). (P , 0.05) higher after Palatinose admin- compared with 1,2-linked sucrose. Accordingly, insulin secretion was 55% istration in comparison to that following Palatinose intake reduced postprandial lower after Palatinose ingestion com- sucrose administration (Fig. 1F and G). glucose-dependent insulinotropic pep- paredwithsucroseintake(Fig.1B). We show the beneficial effects of (GIP) and insulin release in mice (3). We observed an initial small increase Palatinose on glucose metabolism and re- Postprandial insulinsecretionandgly- in glucagon concentrations during the duced insulin secretion without influence cemic excursions are regulated by the first 15 min and followed by a sharp re- on glucagon levels in T2D subjects. Both stimulation of incretin . These duction until 180 min. There were no sig- elicited almost opposing intestinal peptides are glucagon-like nificant differences in plasma glucagon profiles of GIP and GLP-1, which is well peptide 1 (GLP-1) and GIP (4). levels between sucrose and Palatinose explained by the slow cleavage of the We compared the effects of sucrose loading (Fig. 1C). 1,6- bond in Palatinose as versus Palatinose intake on glucose Following sucrose intake, plasma con- compared with the 1,2-disaccharide metabolism, insulin and glucagon secre- centrations of GIP peaked at 15 min with bond in sucrose by intestinal glucosidases tions, and endogenous responses of incre- 2.8-fold increase (P , 0.001). Responses (5). Therefore, Palatinose bypasses the tins in T2D participants. In a randomized of GIP to Palatinose were dramatically upper intestinal K cells producing GIP within-subject crossover study with $7 smaller and delayed peaking after 60 and reaches the more distally located days washout period, 10 overnight-fasted min with 1.5-fold increase (P , 0.001) L cells producing GLP-1. As glucose and T2D subjects (2 women and 8 men, aged (Fig. 1D). Consequently, the incremental fructose are known to be completely re- 61 6 4.6 years, BMI 32.1 6 4.06 kg/m2) area under the curve (iAUC), which was sorbed, the differences in intestinal hor- received 50 g of Palatinose (BENEO calculated by trapezoid rule, of GIP was mone responses must explain the much

OBSERVATIONS GmbH, Mannheim, Germany) or sucrose substantially reduced by 40% (P , more favorable metabolic profile after – (Sudzucker,¨ Mannheim, Germany) dis- 0.001) following Palatinose intake com- Palatinose intake. Thus, Palatinose solved in 300 mL of tap . Active pared with sucrose intake (Fig. 1E). possesses a favorable profile for diabe- GLP-1 and total GIP were measured using After sucrose intake, GLP-1 concen- tes by lowering postprandial e-LETTERS commercially available ELISA kits (EMD trations briefly increased to a maximum endogenous GIP levels, increasing GLP-1

1Department of , German Institute of , Nuthetal, Germany 2Department for , Diabetes and Nutrition, Charite´–University of Medicine Berlin, Berlin, Germany 3German Center for Diabetes Research, Partner Potsdam and Berlin, Nuthetal, Germany Corresponding author: Andreas F.H. Pfeiffer, [email protected]. Received 31 August 2015 and accepted 5 December 2015. Clinical trial reg. no. NCT02219295, clinicaltrials.org. © 2016 by the American Diabetes Association. Readers may use this article as long as the is properly cited, the use is educational and not for profit, and the work is not altered. care.diabetesjournals.org Keyhani-Nejad and Associates e39

Figure 1—Effects of oral Palatinose (blue circles) and sucrose (red circles) intake on glucose (A), insulin (B), and plasma glucagon (C) concentrations in T2D subjects. Plasma concentrations and iAUCs for GIP (D and E) and GLP-1 (F and G) after oral intake of sucrose (red circles and bars) and Palatinose (blue circles and bars). Values are mean 6 SEM. *P , 0.05, **P , 0.01, and ***P , 0.001 compared with Palatinose. concentrations, and saving insulin secre- M.K. contributed to the study design, subject 2. Holub I, Gostner A, Theis S, et al. Novel tion, which ultimately results in better recruitment, data collection, and drafting of the findings on the metabolic effects of the low management of blood glucose in T2D. manuscript. R.S. researched the data and reviewed glycaemic isomaltulose (Palatinose). and edited the manuscript. O.P. contributed to the Br J Nutr 2010;103:1730–1737 data interpretation and discussion and reviewed 3. Keyhani-Nejad F, Irmler M, Isken F, et al. and edited the manuscript. N.R. contributed to Nutritional strategy to prevent fatty liver and Acknowledgments.Theauthorsthankthestaff the data interpretation and critical review of the insulin resistance independent of by of the Clinical Research Unit at the German manuscript. A.F.H.P. contributed to the study reducing glucose-dependent insulinotropic Institute of Human Nutrition Potsdam-Rehbrucke¨ conceptualization and design, data interpretation, polypeptide responses in mice. Diabetologia and the patients for their contribution. The and critical review of the manuscript. A.F.H.P. is the 2015;58:374–383 authors are grateful to Katrin Sprengel, from guarantor of this work and, as such, had full access 4. Nauck MA, Bartels E, Orskov C, Ebert R, German Institute of Human Nutrition, for her to all the data in the study and takes responsibility Creutzfeldt W. Additive insulinotropic effects excellent technical assistance. for the integrity of the data and the accuracy of the of exogenous synthetic human gastric inhibitory Funding. This work was funded by grants data analysis. polypeptide and glucagon-like peptide-1-(7-36) awarded by the Federal Ministry of Education amide infused at near-physiological insulino- and Research of Germany (BMBF grant no. References tropic and glucose concentrations. J 0315669) and the German Research Foundation 1.BasuS,YoffeP,HillsN,LustigRH.The Clin Endocrinol Metab 1993;76:912–917 (DFG Pf 164/14-2). relationship of sugar to population-level dia- 5. Lina BA, Jonker D, Kozianowski G. Isomaltulose Author Contributions. F.K.-N. contributed to betes prevalence: an econometric analysis of (Palatinose): a review of biological and toxico- the data collection, statistical analysis, data repeated cross-sectional data. PLoS One 2013; logical studies. Chem Toxicol 2002;40: interpretation, and drafting of the manuscript. 8:e57873 1375–1381