Intestinal Sweet Taste Receptor Function and Adaptation to Dietary Sugars and Sweeteners

NCT ID: NCT02835859

Last Updated: 2020-08-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-08-31

Study Completion Date

2017-09-30

Brief Summary

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The purpose of this study is to collect data that will help researchers better understand the various causes of obesity and diabetes; particularly to understand how consumption of NCASs affects the way the body uses nutrients.

Detailed Description

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Conditions

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Diabetes

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Group 1- Oral solution

Participants will be randomly assigned to drink two oral solutions made of different combinations of saccharin, lactisole, acetaminophen, 3-O-methyl glucose, or glucose.

Group Type EXPERIMENTAL

Dietary: saccharin

Intervention Type OTHER

Assess the glycemic and hormonal responses to an oral glucose load preceded by an oral solution of NCASs (saccharin).

Estimate glucose absorptions

Intervention Type OTHER

Indirectly estimate the rate of glucose absorption and gastric emptying by using 3-O-methyglucose (3-OMG) and acetaminophen, respectively.

Interventions

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Dietary: saccharin

Assess the glycemic and hormonal responses to an oral glucose load preceded by an oral solution of NCASs (saccharin).

Intervention Type OTHER

Estimate glucose absorptions

Indirectly estimate the rate of glucose absorption and gastric emptying by using 3-O-methyglucose (3-OMG) and acetaminophen, respectively.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Age 18-65 years inclusive;
2. Men and women;
3. Able to provide written, informed consent;
4. Weight stable (± 3 kg) during the 3 months prior to enrollment;
5. BMI ≤ 25 kg/m2

Exclusion Criteria

1. Diagnosed with any of the following co-morbidities: a) coronary artery disease, angina or heart failure, b) diabetes, c) bleeding disorders, d) infections, e) hepatitis and/or cirrhosis, f) severe asthma or chronic obstructive pulmonary disorder, g) renal insufficiency, h) bariatric surgery, i) inflammatory bowel disease or malabsorption, j) cancer within the last 3 years (except non-melanoma skin cancer or treated cervical carcinoma in situ), k) psychiatric or eating disorders, l) untreated or inadequately controlled thyroid or other endocrine disorders, m) active rheumatoid arthritis or other inflammatory rheumatic disorder;
2. Consumption of more than a can of diet beverage or a spoonful of non-caloric artificial sweeteners weekly (or each equivalent from foods) during the past month.
3. Pregnant or nursing women;
4. Current smokers (smoking within the past 3 months);
5. Known hypersensitivity to saccharin, lactisole, and acetaminophen or any of its exipients;
6. History of difficult blood sample collections or unfavorable anatomy of venous access;
7. Use of medications: a) nitrates, b) beta-blockers, c) digoxin, d) anti-diabetic agents, e) oral, injected or chronic topical steroids (inhaled steroids for mild asthma are acceptable), f) chronic use of aspirin or other non-steroidal anti-inflammatory drugs, g) other drugs known to affect immune or metabolic function and h) orlistat, phentermine or other weight loss or anorectic agents.
8. Blood pressure greater than or equal to 160/100 or less than or equal to 100/50 at screening.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Sanford-Burnham Medical Research Institute

OTHER

Sponsor Role collaborator

AdventHealth Translational Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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George Kyriazis, PhD

Role: PRINCIPAL_INVESTIGATOR

Study Principal Investigator

Locations

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Translational Research Institute for Metabolism and Diabetes

Orlando, Florida, United States

Site Status

Countries

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United States

References

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Swithers SE. Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements. Trends Endocrinol Metab. 2013 Sep;24(9):431-41. doi: 10.1016/j.tem.2013.05.005. Epub 2013 Jul 10.

Reference Type BACKGROUND
PMID: 23850261 (View on PubMed)

Kyriazis GA, Soundarapandian MM, Tyrberg B. Sweet taste receptor signaling in beta cells mediates fructose-induced potentiation of glucose-stimulated insulin secretion. Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):E524-32. doi: 10.1073/pnas.1115183109. Epub 2012 Feb 6.

Reference Type BACKGROUND
PMID: 22315413 (View on PubMed)

Nakagawa Y, Nagasawa M, Yamada S, Hara A, Mogami H, Nikolaev VO, Lohse MJ, Shigemura N, Ninomiya Y, Kojima I. Sweet taste receptor expressed in pancreatic beta-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion. PLoS One. 2009;4(4):e5106. doi: 10.1371/journal.pone.0005106. Epub 2009 Apr 8.

Reference Type BACKGROUND
PMID: 19352508 (View on PubMed)

Masubuchi Y, Nakagawa Y, Ma J, Sasaki T, Kitamura T, Yamamoto Y, Kurose H, Kojima I, Shibata H. A novel regulatory function of sweet taste-sensing receptor in adipogenic differentiation of 3T3-L1 cells. PLoS One. 2013;8(1):e54500. doi: 10.1371/journal.pone.0054500. Epub 2013 Jan 15.

Reference Type BACKGROUND
PMID: 23336004 (View on PubMed)

Simon BR, Parlee SD, Learman BS, Mori H, Scheller EL, Cawthorn WP, Ning X, Gallagher K, Tyrberg B, Assadi-Porter FM, Evans CR, MacDougald OA. Artificial sweeteners stimulate adipogenesis and suppress lipolysis independently of sweet taste receptors. J Biol Chem. 2013 Nov 8;288(45):32475-32489. doi: 10.1074/jbc.M113.514034. Epub 2013 Sep 24.

Reference Type BACKGROUND
PMID: 24068707 (View on PubMed)

Margolskee RF, Dyer J, Kokrashvili Z, Salmon KS, Ilegems E, Daly K, Maillet EL, Ninomiya Y, Mosinger B, Shirazi-Beechey SP. T1R3 and gustducin in gut sense sugars to regulate expression of Na+-glucose cotransporter 1. Proc Natl Acad Sci U S A. 2007 Sep 18;104(38):15075-80. doi: 10.1073/pnas.0706678104. Epub 2007 Aug 27.

Reference Type BACKGROUND
PMID: 17724332 (View on PubMed)

Dyer J, Salmon KS, Zibrik L, Shirazi-Beechey SP. Expression of sweet taste receptors of the T1R family in the intestinal tract and enteroendocrine cells. Biochem Soc Trans. 2005 Feb;33(Pt 1):302-5. doi: 10.1042/BST0330302.

Reference Type BACKGROUND
PMID: 15667333 (View on PubMed)

Jang HJ, Kokrashvili Z, Theodorakis MJ, Carlson OD, Kim BJ, Zhou J, Kim HH, Xu X, Chan SL, Juhaszova M, Bernier M, Mosinger B, Margolskee RF, Egan JM. Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proc Natl Acad Sci U S A. 2007 Sep 18;104(38):15069-74. doi: 10.1073/pnas.0706890104. Epub 2007 Aug 27.

Reference Type BACKGROUND
PMID: 17724330 (View on PubMed)

Mace OJ, Affleck J, Patel N, Kellett GL. Sweet taste receptors in rat small intestine stimulate glucose absorption through apical GLUT2. J Physiol. 2007 Jul 1;582(Pt 1):379-92. doi: 10.1113/jphysiol.2007.130906. Epub 2007 May 10.

Reference Type BACKGROUND
PMID: 17495045 (View on PubMed)

Fujita Y, Wideman RD, Speck M, Asadi A, King DS, Webber TD, Haneda M, Kieffer TJ. Incretin release from gut is acutely enhanced by sugar but not by sweeteners in vivo. Am J Physiol Endocrinol Metab. 2009 Mar;296(3):E473-9. doi: 10.1152/ajpendo.90636.2008. Epub 2008 Dec 23.

Reference Type BACKGROUND
PMID: 19106249 (View on PubMed)

Ma J, Bellon M, Wishart JM, Young R, Blackshaw LA, Jones KL, Horowitz M, Rayner CK. Effect of the artificial sweetener, sucralose, on gastric emptying and incretin hormone release in healthy subjects. Am J Physiol Gastrointest Liver Physiol. 2009 Apr;296(4):G735-9. doi: 10.1152/ajpgi.90708.2008. Epub 2009 Feb 12.

Reference Type BACKGROUND
PMID: 19221011 (View on PubMed)

Brown AW, Bohan Brown MM, Onken KL, Beitz DC. Short-term consumption of sucralose, a nonnutritive sweetener, is similar to water with regard to select markers of hunger signaling and short-term glucose homeostasis in women. Nutr Res. 2011 Dec;31(12):882-8. doi: 10.1016/j.nutres.2011.10.004.

Reference Type BACKGROUND
PMID: 22153513 (View on PubMed)

Steinert RE, Frey F, Topfer A, Drewe J, Beglinger C. Effects of carbohydrate sugars and artificial sweeteners on appetite and the secretion of gastrointestinal satiety peptides. Br J Nutr. 2011 May;105(9):1320-8. doi: 10.1017/S000711451000512X. Epub 2011 Jan 24.

Reference Type BACKGROUND
PMID: 21255472 (View on PubMed)

Brown RJ, Walter M, Rother KI. Ingestion of diet soda before a glucose load augments glucagon-like peptide-1 secretion. Diabetes Care. 2009 Dec;32(12):2184-6. doi: 10.2337/dc09-1185. Epub 2009 Oct 6.

Reference Type BACKGROUND
PMID: 19808921 (View on PubMed)

Pepino MY, Klein S. Response to comment on Pepino et al. Sucralose affects glycemic and hormonal responses to an oral glucose load. Diabetes care 2013;36:2530-2535. Diabetes Care. 2014 Jun;37(6):e149. doi: 10.2337/dc14-0268. No abstract available.

Reference Type BACKGROUND
PMID: 24855177 (View on PubMed)

Brown RJ, Walter M, Rother KI. Effects of diet soda on gut hormones in youths with diabetes. Diabetes Care. 2012 May;35(5):959-64. doi: 10.2337/dc11-2424. Epub 2012 Mar 12.

Reference Type BACKGROUND
PMID: 22410815 (View on PubMed)

Gerspach AC, Steinert RE, Schonenberger L, Graber-Maier A, Beglinger C. The role of the gut sweet taste receptor in regulating GLP-1, PYY, and CCK release in humans. Am J Physiol Endocrinol Metab. 2011 Aug;301(2):E317-25. doi: 10.1152/ajpendo.00077.2011. Epub 2011 May 3.

Reference Type BACKGROUND
PMID: 21540445 (View on PubMed)

Steinert RE, Gerspach AC, Gutmann H, Asarian L, Drewe J, Beglinger C. The functional involvement of gut-expressed sweet taste receptors in glucose-stimulated secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). Clin Nutr. 2011 Aug;30(4):524-32. doi: 10.1016/j.clnu.2011.01.007. Epub 2011 Feb 15.

Reference Type BACKGROUND
PMID: 21324568 (View on PubMed)

Chaikomin R, Doran S, Jones KL, Feinle-Bisset C, O'Donovan D, Rayner CK, Horowitz M. Initially more rapid small intestinal glucose delivery increases plasma insulin, GIP, and GLP-1 but does not improve overall glycemia in healthy subjects. Am J Physiol Endocrinol Metab. 2005 Sep;289(3):E504-7. doi: 10.1152/ajpendo.00099.2005. Epub 2005 May 10.

Reference Type BACKGROUND
PMID: 15886226 (View on PubMed)

Little TJ, Pilichiewicz AN, Russo A, Phillips L, Jones KL, Nauck MA, Wishart J, Horowitz M, Feinle-Bisset C. Effects of intravenous glucagon-like peptide-1 on gastric emptying and intragastric distribution in healthy subjects: relationships with postprandial glycemic and insulinemic responses. J Clin Endocrinol Metab. 2006 May;91(5):1916-23. doi: 10.1210/jc.2005-2220. Epub 2006 Feb 21.

Reference Type BACKGROUND
PMID: 16492694 (View on PubMed)

Shirazi-Beechey SP, Moran AW, Batchelor DJ, Daly K, Al-Rammahi M. Glucose sensing and signalling; regulation of intestinal glucose transport. Proc Nutr Soc. 2011 May;70(2):185-93. doi: 10.1017/S0029665111000103. Epub 2011 Mar 30.

Reference Type BACKGROUND
PMID: 21450125 (View on PubMed)

Ma J, Chang J, Checklin HL, Young RL, Jones KL, Horowitz M, Rayner CK. Effect of the artificial sweetener, sucralose, on small intestinal glucose absorption in healthy human subjects. Br J Nutr. 2010 Sep;104(6):803-6. doi: 10.1017/S0007114510001327. Epub 2010 Apr 27.

Reference Type BACKGROUND
PMID: 20420761 (View on PubMed)

Jiang P, Cui M, Zhao B, Liu Z, Snyder LA, Benard LM, Osman R, Margolskee RF, Max M. Lactisole interacts with the transmembrane domains of human T1R3 to inhibit sweet taste. J Biol Chem. 2005 Apr 15;280(15):15238-46. doi: 10.1074/jbc.M414287200. Epub 2005 Jan 24.

Reference Type BACKGROUND
PMID: 15668251 (View on PubMed)

Saccharin and its salts. IARC Monogr Eval Carcinog Risks Hum. 1999;73:517-624. No abstract available.

Reference Type BACKGROUND
PMID: 10804968 (View on PubMed)

Karimian Azari E, Smith KR, Yi F, Osborne TF, Bizzotto R, Mari A, Pratley RE, Kyriazis GA. Inhibition of sweet chemosensory receptors alters insulin responses during glucose ingestion in healthy adults: a randomized crossover interventional study. Am J Clin Nutr. 2017 Apr;105(4):1001-1009. doi: 10.3945/ajcn.116.146001. Epub 2017 Mar 1.

Reference Type DERIVED
PMID: 28251932 (View on PubMed)

Related Links

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http://www.tri-md.org

Florida Hospital Translational Research Institute for Metabolism and Diabetes

Other Identifiers

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TRIMD FH 607060

Identifier Type: -

Identifier Source: org_study_id

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