Effect of Dietary Oils as G-protein-coupled Receptor Agonists on Glucose Tolerance

NCT03774095 | Unknown

• 1 other identifier: PINO 5
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Agonistic activation of fat metabolite responsive G-protein-coupled receptors (GPCR) has been linked to improved glucose metabolism through increased glucose-stimulated-insulin-secreting (GSIS) and incretin release, improved insulin sensitivity and reduced low grade inflammation. In vitro studies have demonstrated that pinolenic acid (20% of pine nut oil) is a potent dual agonist of two GPCRs: free fatty acid receptor-1 (FFA1, formerly GPR40) and free fatty acid receptor-4 (FFA4, formerly GPR120). Moreover, pinolenic acid was able to improve glucose tolerance in mice. G-protein-coupled receptor-119 (GPR119) is known to be activated by the monoacylglycerol: 2-oleoylglycerol (2OG), which is a glycerol molecule attached to oleic acid in the second position. Olive oil contains 61-80% oleic acid, and under digestion 2OG is produced. 2OG has been shown to stimulate GLP-1 release in humans and interestingly, it has recently been suggest that simultaneous activation of GPR119 and FFA1 acts in synergy and enhances enteroendocrine GLP-1 secretion more than the summarized individual agonistic activation. However, this remains to be evaluated in humans. The investigators hypothesize that a combination of pinolenic acid and 2OG administered in delayed release capsules will act in synergy and enhance 1) GLP-1 secretion by stimulating FFA1/FFA4 and GPR119 on enteroendocrine cells causing improved GSIS and increased satiety and 2) enhance GSIS by directly stimulating FFA1 and GPR119 on beta-cells. Study aim: To investigate the acute effects of pinolenic acid combined with 2OG (olive oil) versus pinolenic acid alone on changes in glucose tolerance, insulin, GLP-1, GIP and ghrelin secretion, appetite and gastrointestinal tolerability in overweight and obese healthy humans.

Conditions

Type 2 Diabetes Mellitus; Obesity

Keywords

incretins; Fat metabolites; Free fatty acid receptors; G-protein-coupled receptors

Outcome Measures

Primary Outcomes (8)

• Glucose

  Glucose area under the curve

  6 hours

• Insulin

  Insulin area under the curve

  6 hours

• C-peptide

  C-peptide area under the curve

  6 hours

• GLP-1

  GLP-1 area under the curve

  6 hours

• GIP

  GIP area under the curve

  6 hours

• Ghrelin

  Ghrelin area under the curve

  6 hours

• Appetite

  Appetite is measured by the use of Visual analog scales. Respondents specify their level of agreement to a statement on hunger, satiety, fullness, prospective food consumption and thirst by indicating a position along a continuous 100 mm line between two end-points (0 and 100 mm) which represent the extreme feelings related to the statement. In example: How hungry do you feel? 0mm represents: Not hungry at all and 100 mm represents: I have never been hungrier.

  6 hours

• Gastrointestinal tolerability

  Gastrointestinal tolerability is measured by the use of Visual analog scales. Respondents specify their level of nausea, flatulence, abdominal pain, diarrhea and constipation by indicating a position along a continuous 100 mm line between two end-points (0 and 100 mm) which represent the extreme feelings related to the symptom in question. In example: Have you been constipated? 0mm represents: No,not at all and 100 mm represents: Yes, severely.

  24 hours

Study Arms (3)

No oil

NO INTERVENTION

6-hour oral glucose tolerance test

Hydrolyzed pine nut oil

ACTIVE COMPARATOR

6g hydrolyzed pine nut oil in delayed release capsules given 30 min prior to an 6-hour oral glucose tolerance test

Dietary Supplement: Hydrolyzed pine nut oil

Hydrolyzed pine nut oil and olive oil

ACTIVE COMPARATOR

3g hydrolyzed pine nut oil and 3g olive oil in delayed release capsules given 30 min prior to an 6-hour oral glucose tolerance test

Dietary Supplement: Hydrolyzed pine nut oil and olive oil

Interventions

Hydrolyzed pine nut oil DIETARY_SUPPLEMENT

Given 30 min prior to oral glucose tolerance test

Hydrolyzed pine nut oil

Hydrolyzed pine nut oil and olive oil DIETARY_SUPPLEMENT

Given 30 min prior to oral glucose tolerance test

Hydrolyzed pine nut oil and olive oil

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

Sponsors & Collaborators

• Karina Vejrum Sørensen: lead

Study Sites (1)

Odense University Hospital

Odense, 5000, Denmark

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Obesity

Interventions

Olive Oil

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Fats, Unsaturated; Plant Oils; Oils; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Kurt Hø, MD

  Odense University Hospital/ University of Southern Denmark

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Karina Sørensen, MSc

CONTACT

+45 65413422; karina.vejrum.sorensen@rsyd.dk

Kurt Højlund, MD

CONTACT

+45 65413422

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MSc

Model Details: Cross-over study of 3 interventions; 1) no oil intake, 2)6g hydrolyzed pine nut oil and 3) combined intake of 3g hydrolyzed pine nut oil and 3g olive oil 30 minutes prior to an 6-hours oral glucose tolerance test (75g glucose).

Study Record Dates

• First Submitted: December 11, 2018
• First Posted: December 12, 2018
• Study Start: June 11, 2018
• Primary Completion: December 30, 2018
• Study Completion: December 30, 2018
• Last Updated: December 14, 2018

Record last verified: 2018-12

Locations

DK (1)