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      Insulinotropic Effects of Whey: Mechanisms of Action, Recent Clinical Trials, and Clinical Applications

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      Annals of Nutrition and Metabolism

      S. Karger AG

      Insulin, Whey, Hyperglycemia, Diabetes

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          Abstract

          Background: The insulinotropic effect of whey protein is not fully understood and has clinical implications in the regulation of chronic and acute hyperglycemia. Summary: This review describes the composition of whey protein and potential mechanisms through which whey exerts an insulinotropic effect, including increasing the gastric emptying rate, effect on incretin hormones particularly gastric inhibitory peptide and glucagon-like polypeptide-1, and whey's role as a dipeptidyl peptidase IV inhibitor. Recent clinical evidence on the use of whey protein concentrate, isolate and hydrolysate in the management of type 2 diabetes and in the acute care adult population is reviewed. Key Messages: The mechanism through which whey protein exerts its insulinotropic effect is multifactorial. Increasing evidence supports the potential use of whey protein in medical/nutritional therapy to manage glycemia; however, additional research is needed to determine the most appropriate dose, form and delivery method for whey supplementation.

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          Most cited references 39

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          Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus.

          In type-2 diabetes, the overall incretin effect is reduced. The present investigation was designed to compare insulinotropic actions of exogenous incretin hormones (gastric inhibitory peptide [GIP] and glucagon-like peptide 1 [GLP-1] [7-36 amide]) in nine type-2 diabetic patients (fasting plasma glucose 7.8 mmol/liter; hemoglobin A1c 6.3 +/- 0.6%) and in nine age- and weight-matched normal subjects. Synthetic human GIP (0.8 and 2.4 pmol/kg.min over 1 h each), GLP-1 [7-36 amide] (0.4 and 1.2 pmol/kg.min over 1 h each), and placebo were administered under hyperglycemic clamp conditions (8.75 mmol/liter) in separate experiments. Plasma GIP and GLP-1 [7-36 amide] concentrations (radioimmunoassay) were comparable to those after oral glucose with the low, and clearly supraphysiological with the high infusion rates. Both GIP and GLP-1 [7-36 amide] dose-dependently augmented insulin secretion (insulin, C-peptide) in both groups (P < 0.05). With GIP, the maximum effect in type-2 diabetic patients was significantly lower (by 54%; P < 0.05) than in normal subjects. With GLP-1 [7-36 amide] type-2 diabetic patients reached 71% of the increments in C-peptide of normal subjects (difference not significant). Glucagon was lowered during hyperglycemic clamps in normal subjects, but not in type-2 diabetic patients, and further by GLP-1 [7-36 amide] in both groups (P < 0.05), but not by GIP. In conclusion, in mild type-2 diabetes, GLP-1 [7-36 amide], in contrast to GIP, retains much of its insulinotropic activity. It also lowers glucagon concentrations.
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            Effects of whey protein isolate on body composition, lipids, insulin and glucose in overweight and obese individuals.

            The health benefits currently associated with increased dairy intake may be attributable to the whey component of dairy proteins. The present study evaluated the effects of whey protein supplementation on body composition, lipids, insulin and glucose in comparison to casein and glucose (control) supplementation in overweight/obese individuals for 12 weeks. The subjects were randomised to whey protein, casein or glucose supplementation for 12 weeks according to a parallel design. Fasting blood samples and dual-energy X-ray absorptiometry measurements were taken. Seventy men and women with a mean age of 48.4 (SEM 0.86) years and a mean BMI of 31.3 (SEM 0.8) kg/m2 completed the study. Subjects supplemented with whey protein had no significant change in body composition or serum glucose at 12 weeks compared with the control or casein group. Fasting TAG levels were significantly lowered in the whey group compared with the control group at 6 weeks (P = 0.025) and 12 weeks (P = 0.035). There was a significant decrease in total cholesterol and LDL cholesterol at week 12 in the whey group compared with the casein (P = 0.026 and 0.045, respectively) and control groups (P < 0.001 and 0.003, respectively). Fasting insulin levels and homeostasis model assessment of insulin resistance scores were also significantly decreased in the whey group compared with the control group (P = 0.049 and P = 0.034, respectively). The present study demonstrated that supplementation with whey proteins improves fasting lipids and insulin levels in overweight and obese individuals.
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              Gastric emptying, gastric secretion and enterogastrone response after administration of milk proteins or their peptide hydrolysates in humans.

              The influence of protein fractionation on gastric emptying and rate of appearance of their constituent amino acids in peripheral blood remains unknown. To examine the influence of the degree of protein fractionation on gastric emptying, gastric secretion, amino acid absorption and enterogastrone response, after the intragastric administration of complete cow milk proteins or their respective peptide hydrolysates in man. Six healthy males were randomized to receive one of the following four solutions: whey whole protein (W), casein whole protein (C), whey peptide hydrolysate (WHY) or casein hydrolysate (CAHY). All solutions were matched for volume (600 mL), nitrogen content (9.3 g/L), energy density (1069-1092 kJ/L), osmolality (288-306 mosmol/kg), pH (6.9-7.0) and temperature (37 degrees C). Solutions were emptied at similar rates, with mean half-times of (mean +/- SEM) 21.4 +/- 1.3, 19.3 +/- 2.2, 18.0 +/- 2.5 and 19.4 +/- 2.8 min, for the WHY, CAHY, C and W, respectively. The rates of intestinal absorption of water and amino acids were similar with the exception of the casein protein solution, for which the speed of intestinal amino acid absorption was slower (p < 0.05). The peptide hydrolysates elicited about 50% more gastric secretion than the whole protein solutions ( p < 0.05),which was accompanied by higher glucose-dependent insulinotropic polipeptide (GIP) plasma levels during the first 20 min of the gastric emptying process. Similar glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) plasma responses were elicited by the four solutions. The rate of gastric emptying and the plasma GLP-1 and PYY responses to feeding with cow milk protein solutions in humans are independent of the degree of protein fractionation and are not altered by small differences in the amino acid composition or protein solubility. In contrast, the GIP response is accentuated when milk proteins are delivered as peptide hydrolysates.
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                Author and article information

                Journal
                ANM
                Ann Nutr Metab
                10.1159/issn.0250-6807
                Annals of Nutrition and Metabolism
                Ann Nutr Metab
                S. Karger AG (Basel, Switzerland karger@ 123456karger.com http://www.karger.com )
                0250-6807
                1421-9697
                September 2016
                17 August 2016
                : 69
                : 1
                : 56-63
                Affiliations
                Department of Nutrition and Food Science, Texas Woman's University, Denton, Tex., USA
                Article
                ANM2016069001056 Ann Nutr Metab 2016;69:56-63
                10.1159/000448665
                27529642
                © 2016 The Author(s) Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 1, References: 52, Pages: 8
                Categories
                Review Article

                Medicine, General social science

                Diabetes, Hyperglycemia, Whey, Insulin

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