Plasma GLP-1 response in the specified meal or glucose challenge

evidence_span

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experimental_model

Randomized crossover glucose-challenge study in 15 overweight men

exposure

1 g CGA, 12 g decaffeinated coffee, 500 mg trigonelline or placebo

limitations

Acute small male-only study; coffee and isolated ingredients are separate exposures. No overall incretin effect is not proof of zero effect at every dose or duration.

nutrient_topic

Chlorogenic acid research collection; topical membership is not evidence of a direct dietary effect. · Chlorogenic acid / 5-O-caffeoylquinic acid

organism

Human

plain_language

An incretin-stimulation claim needs to acknowledge this human null result.

primary_references

[chlorogenic_acid-p21299855] Acute effects of decaffeinated coffee and the major coffee components chlorogenic acid and trigonelline on incretin hormones. (2011). https://pubmed.ncbi.nlm.nih.gov/21299855/ DOI: 10.1186/1743-7075-8-10

tissue_or_cell_type

Plasma incretin responses during OGTT

Chlorogenic acid: metabolism, signaling and nutrient connections (2026-09-17) · lines 893–904

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized crossover glucose-challenge study in 15 overweight men · source_derived_draft · unverified_draft

### chlorogenic_acid-glp1-null Isolated CGA did not significantly alter the overall GLP-1 response. Condition category: normal nutrient_topic: Chlorogenic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: An incretin-stimulation claim needs to acknowledge this human null result. organism: Human tissue_or_cell_type: Plasma incretin responses during OGTT experimental_model: Randomized crossover glucose-challenge study in 15 overweight men limitations: Acute small male-only study; coffee and isolated ingredients are separate exposures. No overall incretin effect is not proof of zero effect at every dose or duration. exposure: 1 g CGA, 12 g decaffeinated coffee, 500 mg trigonelline or placebo evidence_span: {"source_cache": "artifacts/chlorogenic_acid-research/21299855.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9a6f69bf52ab0f7823e1cc585e4565765348c7a3e9bab03a88a0e7cb020306c3", "start_char": 0, "end_char": 1086, "text_sha256": "9a6f69bf52ab0f7823e1cc585e4565765348c7a3e9bab03a88a0e7cb020306c3"} [chlorogenic_acid-p21299855] Acute effects of decaffeinated coffee and the major coffee components chlorogenic acid and trigonelline on incretin hormones. (2011). https://pubmed.ncbi.nlm.nih.gov/21299855/ DOI: 10.1186/1743-7075-8-10

evidence_span

{"source_cache": "artifacts/chlorogenic_acid-research/36501092.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dcd5f0afb16bd6f9c61c91be9220e18751e0e34c8eac1aeeb5613649ed2d001b", "start_char": 0, "end_char": 1425, "text_sha256": "dcd5f0afb16bd6f9c61c91be9220e18751e0e34c8eac1aeeb5613649ed2d001b"}

experimental_model

Randomized crossover beverage intervention in 11 men

exposure

Three weeks: 620 mg green tea catechins plus 373 mg CGAs plus 119 mg caffeine; control 119 mg caffeine

limitations

A multi-ingredient formulation with a small sample. Effects cannot be assigned to CGA alone or treated as a contradiction of an acute isolated-CGA experiment.

nutrient_topic

Chlorogenic acid research collection; topical membership is not evidence of a direct dietary effect. · Chlorogenic acid / 5-O-caffeoylquinic acid

organism

Human

plain_language

The complete tested combination is the exposure.

primary_references

[chlorogenic_acid-p36501092] Effects of Ingesting Both Catechins and Chlorogenic Acids on Glucose, Incretin, and Insulin Sensitivity in Healthy Men: A Randomized, Double-Blinded, Placebo-Controlled Crossover Trial. (2022). https://pubmed.ncbi.nlm.nih.gov/36501092/ DOI: 10.3390/nu14235063

tissue_or_cell_type

Postprandial glucose, insulin and incretin measurements

Chlorogenic acid: metabolism, signaling and nutrient connections (2026-09-17) · lines 1062–1073

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized crossover beverage intervention in 11 men · source_derived_draft · unverified_draft

### chlorogenic_acid-mixture-glp1 The combined beverage increased postprandial GLP-1 relative to its caffeine control. Condition category: normal nutrient_topic: Chlorogenic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The complete tested combination is the exposure. organism: Human tissue_or_cell_type: Postprandial glucose, insulin and incretin measurements experimental_model: Randomized crossover beverage intervention in 11 men limitations: A multi-ingredient formulation with a small sample. Effects cannot be assigned to CGA alone or treated as a contradiction of an acute isolated-CGA experiment. exposure: Three weeks: 620 mg green tea catechins plus 373 mg CGAs plus 119 mg caffeine; control 119 mg caffeine evidence_span: {"source_cache": "artifacts/chlorogenic_acid-research/36501092.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dcd5f0afb16bd6f9c61c91be9220e18751e0e34c8eac1aeeb5613649ed2d001b", "start_char": 0, "end_char": 1425, "text_sha256": "dcd5f0afb16bd6f9c61c91be9220e18751e0e34c8eac1aeeb5613649ed2d001b"} [chlorogenic_acid-p36501092] Effects of Ingesting Both Catechins and Chlorogenic Acids on Glucose, Incretin, and Insulin Sensitivity in Healthy Men: A Randomized, Double-Blinded, Placebo-Controlled Crossover Trial. (2022). https://pubmed.ncbi.nlm.nih.gov/36501092/ DOI: 10.3390/nu14235063

evidence_span

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experimental_model

Isolated perfused rat colon with luminal and vascular short-chain fatty acid infusion and receptor pharmacology

exposure

Acetate, propionate and butyrate perfused luminally or vascularly, with FFAR2/FFAR3 agonists, an FFAR3 antagonist, nifedipine, diazoxide and 2,4-dinitrophenol

limitations

An isolated organ preparation with an intact blood supply. It reaches the opposite mechanistic conclusion from the knockout work in this collection and is why the receptor route is recorded as disputed.

nutrient_topic

Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. · Acetic acid

organism

Rat

plain_language

Acetate and butyrate released the hormone from the isolated gut; propionate did not.

primary_references

[acetate-p29494208] The impact of short-chain fatty acids on GLP-1 and PYY secretion from the isolated perfused rat colon. (2018). https://pubmed.ncbi.nlm.nih.gov/29494208/ DOI: 10.1152/ajpgi.00346.2017

tissue_or_cell_type

Colon

Acetic acid: the ingested acid, the receptors acetate binds, the acetyl-CoA it becomes, and the acetyl groups that reach histones (2026-09-21) · lines 329–340

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated perfused rat colon with luminal and vascular short-chain fatty acid infusion and receptor pharmacology · source_derived_draft · unverified_draft

### acetate-acetate-glp1-perfused Luminal and especially vascular infusion of acetate and butyrate significantly increased colonic GLP-1 secretion and to a minor extent PYY secretion in the isolated perfused rat colon, but only after enhancement of intracellular cAMP, while propionate affected neither GLP-1 nor PYY by either route. Condition category: normal nutrient_topic: Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. plain_language: Acetate and butyrate released the hormone from the isolated gut; propionate did not. organism: Rat tissue_or_cell_type: Colon experimental_model: Isolated perfused rat colon with luminal and vascular short-chain fatty acid infusion and receptor pharmacology limitations: An isolated organ preparation with an intact blood supply. It reaches the opposite mechanistic conclusion from the knockout work in this collection and is why the receptor route is recorded as disputed. exposure: Acetate, propionate and butyrate perfused luminally or vascularly, with FFAR2/FFAR3 agonists, an FFAR3 antagonist, nifedipine, diazoxide and 2,4-dinitrophenol evidence_span: {"source_cache": "artifacts/acetate-research/29494208.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9f8def7b832fdd5d5aed67891c84b18b597d558d9361a92412ccc44264b88126", "start_char": 0, "end_char": 2445, "text_sha256": "9f8def7b832fdd5d5aed67891c84b18b597d558d9361a92412ccc44264b88126"} [acetate-p29494208] The impact of short-chain fatty acids on GLP-1 and PYY secretion from the isolated perfused rat colon. (2018). https://pubmed.ncbi.nlm.nih.gov/29494208/ DOI: 10.1152/ajpgi.00346.2017

evidence_span

{"source_cache": "artifacts/acetate-research/27966574.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7c0282e2d96baff8a6dde713af91c9df8641d7075c78cf1453ee7d74f6016cd3", "start_char": 0, "end_char": 1724, "text_sha256": "7c0282e2d96baff8a6dde713af91c9df8641d7075c78cf1453ee7d74f6016cd3"}

experimental_model

Randomised single-blind crossover in 13 overweight or obese and 12 lean humans

exposure

75 g glucose alone, or with 24 g inulin or 28.2 g resistant starch, with blood sampled over 6 hours

limitations

The ligand did rise: inulin significantly increased the 4 to 6 hour short-chain fatty acid area under the curve. The authors note that a longer adaptation or a larger sample might give a different answer.

nutrient_topic

Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. · Acetic acid

organism

Human

plain_language

In people the fatty acids rose and the two appetite hormones did not move, though ghrelin fell.

primary_references

[acetate-p27966574] Acute increases in serum colonic short-chain fatty acids elicited by inulin do not increase GLP-1 or PYY responses but may reduce ghrelin in lean and overweight humans. (2017). https://pubmed.ncbi.nlm.nih.gov/27966574/ DOI: 10.1038/ejcn.2016.249

tissue_or_cell_type

Whole body

Acetic acid: the ingested acid, the receptors acetate binds, the acetyl-CoA it becomes, and the acetyl groups that reach histones (2026-09-21) · lines 368–379

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomised single-blind crossover in 13 overweight or obese and 12 lean humans · source_derived_draft · unverified_draft

### acetate-no-human-glp1 Inulin but not resistant starch significantly increased the short-chain fatty acid area under the curve from 4 to 6 hours, yet neither affected the GLP-1 or PYY area under the curve, while ghrelin at 6 hours after inulin was significantly lower than after glucose and the change in short-chain fatty acid area was negatively related to the change in ghrelin area; responses did not differ significantly between lean and overweight subjects. Condition category: normal nutrient_topic: Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. plain_language: In people the fatty acids rose and the two appetite hormones did not move, though ghrelin fell. organism: Human tissue_or_cell_type: Whole body experimental_model: Randomised single-blind crossover in 13 overweight or obese and 12 lean humans limitations: The ligand did rise: inulin significantly increased the 4 to 6 hour short-chain fatty acid area under the curve. The authors note that a longer adaptation or a larger sample might give a different answer. exposure: 75 g glucose alone, or with 24 g inulin or 28.2 g resistant starch, with blood sampled over 6 hours evidence_span: {"source_cache": "artifacts/acetate-research/27966574.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7c0282e2d96baff8a6dde713af91c9df8641d7075c78cf1453ee7d74f6016cd3", "start_char": 0, "end_char": 1724, "text_sha256": "7c0282e2d96baff8a6dde713af91c9df8641d7075c78cf1453ee7d74f6016cd3"} [acetate-p27966574] Acute increases in serum colonic short-chain fatty acids elicited by inulin do not increase GLP-1 or PYY responses but may reduce ghrelin in lean and overweight humans. (2017). https://pubmed.ncbi.nlm.nih.gov/27966574/ DOI: 10.1038/ejcn.2016.249

evidence_span

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experimental_model

Isolated perfused rat colon with luminal and vascular short-chain fatty acid infusion and receptor pharmacology

exposure

Acetate, propionate and butyrate perfused luminally or vascularly, with FFAR2/FFAR3 agonists, an FFAR3 antagonist, nifedipine, diazoxide and 2,4-dinitrophenol

limitations

An isolated organ preparation with an intact blood supply. It reaches the opposite mechanistic conclusion from the knockout work in this collection and is why the receptor route is recorded as disputed.

nutrient_topic

Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. · Acetic acid

organism

Rat

plain_language

Blocking the receptors changed nothing, while blocking energy production abolished the response.

primary_references

[acetate-p29494208] The impact of short-chain fatty acids on GLP-1 and PYY secretion from the isolated perfused rat colon. (2018). https://pubmed.ncbi.nlm.nih.gov/29494208/ DOI: 10.1152/ajpgi.00346.2017

tissue_or_cell_type

Colon

Acetic acid: the ingested acid, the receptors acetate binds, the acetyl-CoA it becomes, and the acetyl groups that reach histones (2026-09-21) · lines 342–353

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated perfused rat colon with luminal and vascular short-chain fatty acid infusion and receptor pharmacology · source_derived_draft · unverified_draft

### acetate-receptor-not-required A FFAR2- and FFAR3-specific agonist had no effect on colonic GLP-1 output and a FFAR3 antagonist did not decrease the short-chain fatty acid-induced GLP-1 response, whereas the calcium channel blocker nifedipine, the KATP-channel opener diazoxide and the ATP synthesis inhibitor 2,4-dinitrophenol completely abolished the responses, leading the authors to conclude that the fatty acids are metabolised and function as a colonocyte energy source rather than acting through the receptors. Condition category: normal nutrient_topic: Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. plain_language: Blocking the receptors changed nothing, while blocking energy production abolished the response. organism: Rat tissue_or_cell_type: Colon experimental_model: Isolated perfused rat colon with luminal and vascular short-chain fatty acid infusion and receptor pharmacology limitations: An isolated organ preparation with an intact blood supply. It reaches the opposite mechanistic conclusion from the knockout work in this collection and is why the receptor route is recorded as disputed. exposure: Acetate, propionate and butyrate perfused luminally or vascularly, with FFAR2/FFAR3 agonists, an FFAR3 antagonist, nifedipine, diazoxide and 2,4-dinitrophenol evidence_span: {"source_cache": "artifacts/acetate-research/29494208.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9f8def7b832fdd5d5aed67891c84b18b597d558d9361a92412ccc44264b88126", "start_char": 0, "end_char": 2445, "text_sha256": "9f8def7b832fdd5d5aed67891c84b18b597d558d9361a92412ccc44264b88126"} [acetate-p29494208] The impact of short-chain fatty acids on GLP-1 and PYY secretion from the isolated perfused rat colon. (2018). https://pubmed.ncbi.nlm.nih.gov/29494208/ DOI: 10.1152/ajpgi.00346.2017

evidence_span

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experimental_model

Wistar rats, C57BL6 mice and FFA2 knockout mice, with colonic crypt cultures and portal vein sampling

exposure

Propionate applied to colonic crypt cultures and infused into the colon, with FFA2 deletion as the test of mediation

limitations

Establishes the receptor-to-hormone step in rodents using propionate rather than acetate. The knockout is the strength of the design.

nutrient_topic

Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. · Acetic acid

organism

Rat and mouse

plain_language

In rodents the receptor is what releases the two gut hormones; delete it and the response goes.

primary_references

[acetate-p25109781] The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents. (2015). https://pubmed.ncbi.nlm.nih.gov/25109781/ DOI: 10.1038/ijo.2014.153

tissue_or_cell_type

Colon

Acetic acid: the ingested acid, the receptors acetate binds, the acetyl-CoA it becomes, and the acetyl groups that reach histones (2026-09-21) · lines 316–327

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Wistar rats, C57BL6 mice and FFA2 knockout mice, with colonic crypt cultures and portal vein sampling · source_derived_draft · unverified_draft

### acetate-scfa-glp1-rodent Propionate stimulated secretion of both peptide YY and GLP-1 from wild-type murine colonic crypt cultures and this effect was significantly attenuated in cultures from FFA2 knockout mice, while intra-colonic infusion of propionate elevated both hormones in portal vein plasma in rats and mice but did not significantly stimulate their release in FFA2 knockout mice. Condition category: normal nutrient_topic: Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. plain_language: In rodents the receptor is what releases the two gut hormones; delete it and the response goes. organism: Rat and mouse tissue_or_cell_type: Colon experimental_model: Wistar rats, C57BL6 mice and FFA2 knockout mice, with colonic crypt cultures and portal vein sampling limitations: Establishes the receptor-to-hormone step in rodents using propionate rather than acetate. The knockout is the strength of the design. exposure: Propionate applied to colonic crypt cultures and infused into the colon, with FFA2 deletion as the test of mediation evidence_span: {"source_cache": "artifacts/acetate-research/25109781.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c3c934644f9308be7b2c26f969858debd0d1dbf19bee7e307e529d392fe135d6", "start_char": 0, "end_char": 1621, "text_sha256": "c3c934644f9308be7b2c26f969858debd0d1dbf19bee7e307e529d392fe135d6"} [acetate-p25109781] The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents. (2015). https://pubmed.ncbi.nlm.nih.gov/25109781/ DOI: 10.1038/ijo.2014.153

dose

Meal with 50 g added sucrose in 200 mL; with or without 100 mg acarbose before meal

duration

GLP-1 through 60 minutes; ApoB-48 at 120 minutes

evidence_access

Primary full-text methods/results and metadata inspected.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Healthy Japanese men; 21 total, 12 in acarbose comparison

exposure_scope

Sucrose-containing mixed meal, drug and peptide response

limitations

Mixed meal includes starch, protein and fat. Association does not prove intact sucrose sensing by human L cells or GLP-1 mediation of ApoB-48; proposed paracrine mechanism remains a hypothesis.

nutrient_topic

Sucrose chapter; direct sucrose observations are distinguished from shared component metabolism. · Sucrose

organism

Healthy Japanese men; 21 total, 12 in acarbose comparison

plain_language

Acarbose pretreatment prolonged active GLP-1 elevation to 60 minutes after the sucrose-containing mixed meal.

primary_references

Glucagon-like peptide-1 secretion by direct stimulation of L cells with luminal sugar vs non-nutritive sweetener. (2012). https://pubmed.ncbi.nlm.nih.gov/24843559/ DOI: 10.1111/j.2040-1124.2011.00163.x

route

Oral mixed meal and drug

tissue

Plasma active GLP-1 and ApoB-48 after mixed meal

Sucrose: mechanism of action and metabolic impact (2026-09-20) · lines 271–281

Original AI-assisted source-specific sucrose curation with shared canonical claims retained by identity. Primary-study citations, negative findings, exposure details and limitations preserved. Not publisher full text. · supports · Healthy Japanese men; 21 total, 12 in acarbose comparison · source_derived_draft · unverified_draft

## sucrose-acarbose-glp1 Acarbose pretreatment prolonged active GLP-1 elevation to 60 minutes after the sucrose-containing mixed meal. Model/species: Healthy Japanese men; 21 total, 12 in acarbose comparison Tissue: Plasma active GLP-1 and ApoB-48 after mixed meal Exposure: Meal with 50 g added sucrose in 200 mL; with or without 100 mg acarbose before meal Route: Oral mixed meal and drug Duration: GLP-1 through 60 minutes; ApoB-48 at 120 minutes Exposure scope: Sucrose-containing mixed meal, drug and peptide response Limits: Mixed meal includes starch, protein and fat. Association does not prove intact sucrose sensing by human L cells or GLP-1 mediation of ApoB-48; proposed paracrine mechanism remains a hypothesis. Reference: Glucagon-like peptide-1 secretion by direct stimulation of L cells with luminal sugar vs non-nutritive sweetener. (2012). https://pubmed.ncbi.nlm.nih.gov/24843559/ DOI: 10.1111/j.2040-1124.2011.00163.x Access: Primary full-text methods/results and metadata inspected.

dose

50 versus 5 g sucrose; 5 g plus mixed sucralose/acesulfame/aspartame/erythritol to match sweetness

duration

15-minute comparison; sampling to 60 minutes

evidence_access

Primary full-text methods/results and metadata inspected.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Healthy Japanese men in low-sucrose meal substudy

exposure_scope

Sucrose dose versus matched perceived sweetness

limitations

Methods say n=6 for sweetener substudy, results report n=7; discrepancy preserved. Lower sucrose also lowers calories; this is not a calorie-matched isolated receptor experiment.

nutrient_topic

Sucrose chapter; direct sucrose observations are distinguished from shared component metabolism. · Sucrose

organism

Healthy Japanese men in low-sucrose meal substudy

plain_language

Reducing added sucrose from 50 to 5 g lowered the 15-minute active GLP-1 response to the mixed meal.

primary_references

Glucagon-like peptide-1 secretion by direct stimulation of L cells with luminal sugar vs non-nutritive sweetener. (2012). https://pubmed.ncbi.nlm.nih.gov/24843559/ DOI: 10.1111/j.2040-1124.2011.00163.x

route

Oral mixed meal

tissue

Plasma active GLP-1 after mixed meal

Sucrose: mechanism of action and metabolic impact (2026-09-20) · lines 247–257

Original AI-assisted source-specific sucrose curation with shared canonical claims retained by identity. Primary-study citations, negative findings, exposure details and limitations preserved. Not publisher full text. · supports · Healthy Japanese men in low-sucrose meal substudy · source_derived_draft · unverified_draft

## sucrose-low-sucrose-glp1 Reducing added sucrose from 50 to 5 g lowered the 15-minute active GLP-1 response to the mixed meal. Model/species: Healthy Japanese men in low-sucrose meal substudy Tissue: Plasma active GLP-1 after mixed meal Exposure: 50 versus 5 g sucrose; 5 g plus mixed sucralose/acesulfame/aspartame/erythritol to match sweetness Route: Oral mixed meal Duration: 15-minute comparison; sampling to 60 minutes Exposure scope: Sucrose dose versus matched perceived sweetness Limits: Methods say n=6 for sweetener substudy, results report n=7; discrepancy preserved. Lower sucrose also lowers calories; this is not a calorie-matched isolated receptor experiment. Reference: Glucagon-like peptide-1 secretion by direct stimulation of L cells with luminal sugar vs non-nutritive sweetener. (2012). https://pubmed.ncbi.nlm.nih.gov/24843559/ DOI: 10.1111/j.2040-1124.2011.00163.x Access: Primary full-text methods/results and metadata inspected.

dose

50 versus 5 g sucrose; 5 g plus mixed sucralose/acesulfame/aspartame/erythritol to match sweetness

duration

15-minute comparison; sampling to 60 minutes

evidence_access

Primary full-text methods/results and metadata inspected.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Healthy Japanese men in low-sucrose meal substudy

exposure_scope

Sucrose dose versus matched perceived sweetness

limitations

Methods say n=6 for sweetener substudy, results report n=7; discrepancy preserved. Lower sucrose also lowers calories; this is not a calorie-matched isolated receptor experiment.

nutrient_topic

Sucrose chapter; direct sucrose observations are distinguished from shared component metabolism. · Sucrose

organism

Healthy Japanese men in low-sucrose meal substudy

plain_language

Matching sweetness with nonnutritive sweeteners did not restore the GLP-1 response lost when meal sucrose was reduced.

primary_references

Glucagon-like peptide-1 secretion by direct stimulation of L cells with luminal sugar vs non-nutritive sweetener. (2012). https://pubmed.ncbi.nlm.nih.gov/24843559/ DOI: 10.1111/j.2040-1124.2011.00163.x

route

Oral mixed meal

tissue

Plasma active GLP-1 after mixed meal

Sucrose: mechanism of action and metabolic impact (2026-09-20) · lines 259–269

Original AI-assisted source-specific sucrose curation with shared canonical claims retained by identity. Primary-study citations, negative findings, exposure details and limitations preserved. Not publisher full text. · supports · Healthy Japanese men in low-sucrose meal substudy · source_derived_draft · unverified_draft

## sucrose-sweetness-glp1-null Matching sweetness with nonnutritive sweeteners did not restore the GLP-1 response lost when meal sucrose was reduced. Model/species: Healthy Japanese men in low-sucrose meal substudy Tissue: Plasma active GLP-1 after mixed meal Exposure: 50 versus 5 g sucrose; 5 g plus mixed sucralose/acesulfame/aspartame/erythritol to match sweetness Route: Oral mixed meal Duration: 15-minute comparison; sampling to 60 minutes Exposure scope: Sucrose dose versus matched perceived sweetness Limits: Methods say n=6 for sweetener substudy, results report n=7; discrepancy preserved. Lower sucrose also lowers calories; this is not a calorie-matched isolated receptor experiment. Reference: Glucagon-like peptide-1 secretion by direct stimulation of L cells with luminal sugar vs non-nutritive sweetener. (2012). https://pubmed.ncbi.nlm.nih.gov/24843559/ DOI: 10.1111/j.2040-1124.2011.00163.x Access: Primary full-text methods/results and metadata inspected.

evidence_span

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experimental_model

Two randomised crossover trials of delayed-release metformin targeted to the ileum

exposure

Delayed-release versus immediate-release metformin over 5 to 7 day periods

limitations

The dissociation of effect from plasma exposure is the key observation. Funded by the manufacturer of the delayed-release formulation, which the record retains.

nutrient_topic

Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin

organism

Human

plain_language

Gut hormones rose alongside the glucose effect.

primary_references

[metformin-p27216492] Once-daily delayed-release metformin lowers plasma glucose and enhances fasting and postprandial GLP-1 and PYY: results from two randomised trials. (2016). https://pubmed.ncbi.nlm.nih.gov/27216492/ DOI: 10.1007/s00125-016-3992-6

tissue_or_cell_type

Distal small intestine

Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 840–851

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two randomised crossover trials of delayed-release metformin targeted to the ileum · source_derived_draft · unverified_draft

### metformin-ileal-glp1 Fasting and postprandial GLP-1 rose with all metformin treatments, with day-5 to baseline AUC ratios of 1.6-1.9. Condition category: normal nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: Gut hormones rose alongside the glucose effect. organism: Human tissue_or_cell_type: Distal small intestine experimental_model: Two randomised crossover trials of delayed-release metformin targeted to the ileum limitations: The dissociation of effect from plasma exposure is the key observation. Funded by the manufacturer of the delayed-release formulation, which the record retains. exposure: Delayed-release versus immediate-release metformin over 5 to 7 day periods evidence_span: {"source_cache": "artifacts/metformin-research/27216492.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c874a5c13e2e709b4b36040f281e2b187e7956b4610decddc35403170c0ed45d", "start_char": 0, "end_char": 3863, "text_sha256": "c874a5c13e2e709b4b36040f281e2b187e7956b4610decddc35403170c0ed45d"} [metformin-p27216492] Once-daily delayed-release metformin lowers plasma glucose and enhances fasting and postprandial GLP-1 and PYY: results from two randomised trials. (2016). https://pubmed.ncbi.nlm.nih.gov/27216492/ DOI: 10.1007/s00125-016-3992-6

evidence_span

{"source_cache": "artifacts/metformin-research/27216492.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c874a5c13e2e709b4b36040f281e2b187e7956b4610decddc35403170c0ed45d", "start_char": 0, "end_char": 3863, "text_sha256": "c874a5c13e2e709b4b36040f281e2b187e7956b4610decddc35403170c0ed45d"}

experimental_model

Two randomised crossover trials of delayed-release metformin targeted to the ileum

exposure

Delayed-release versus immediate-release metformin over 5 to 7 day periods

limitations

The dissociation of effect from plasma exposure is the key observation. Funded by the manufacturer of the delayed-release formulation, which the record retains.

nutrient_topic

Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin

organism

Human

plain_language

Gut hormones rose alongside the glucose effect.

primary_references

[metformin-p27216492] Once-daily delayed-release metformin lowers plasma glucose and enhances fasting and postprandial GLP-1 and PYY: results from two randomised trials. (2016). https://pubmed.ncbi.nlm.nih.gov/27216492/ DOI: 10.1007/s00125-016-3992-6

tissue_or_cell_type

Distal small intestine

Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 853–864

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two randomised crossover trials of delayed-release metformin targeted to the ileum · source_derived_draft · unverified_draft

### metformin-ileal-pyy Fasting and postprandial PYY rose with all metformin treatments, with day-5 to baseline AUC ratios of 1.4-1.5. Condition category: normal nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: Gut hormones rose alongside the glucose effect. organism: Human tissue_or_cell_type: Distal small intestine experimental_model: Two randomised crossover trials of delayed-release metformin targeted to the ileum limitations: The dissociation of effect from plasma exposure is the key observation. Funded by the manufacturer of the delayed-release formulation, which the record retains. exposure: Delayed-release versus immediate-release metformin over 5 to 7 day periods evidence_span: {"source_cache": "artifacts/metformin-research/27216492.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c874a5c13e2e709b4b36040f281e2b187e7956b4610decddc35403170c0ed45d", "start_char": 0, "end_char": 3863, "text_sha256": "c874a5c13e2e709b4b36040f281e2b187e7956b4610decddc35403170c0ed45d"} [metformin-p27216492] Once-daily delayed-release metformin lowers plasma glucose and enhances fasting and postprandial GLP-1 and PYY: results from two randomised trials. (2016). https://pubmed.ncbi.nlm.nih.gov/27216492/ DOI: 10.1007/s00125-016-3992-6

evidence_span

{"source_cache": "artifacts/acetate-research/23885020.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b834455e11c2b8fa3c4c19c5d01375815e46c3b0f8e25eb184f0eaa6a51c749e", "start_char": 0, "end_char": 2144, "text_sha256": "b834455e11c2b8fa3c4c19c5d01375815e46c3b0f8e25eb184f0eaa6a51c749e"}

experimental_model

Transgenic monomeric red fluorescent protein reporter mice with FACS purification and quantitative PCR

exposure

Cell-type resolved expression of FFAR2 and FFAR3 reporters, with receptor-specific synthetic agonists on colonic crypt cultures

limitations

Reporter expression is not the same as receptor protein. The FFAR2 result here is weaker in enteroendocrine cells than the rat immunohistochemistry in this collection reports.

nutrient_topic

Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. · Acetic acid

organism

Mouse

plain_language

FFAR2 turned out to sit mainly on immune cells rather than on the hormone cells, though its agonist still released the hormone.

primary_references

[acetate-p23885020] GPR41/FFAR3 and GPR43/FFAR2 as cosensors for short-chain fatty acids in enteroendocrine cells vs FFAR3 in enteric neurons and FFAR2 in enteric leukocytes. (2013). https://pubmed.ncbi.nlm.nih.gov/23885020/ DOI: 10.1210/en.2013-1142

tissue_or_cell_type

Whole gastrointestinal tract

Acetic acid: the ingested acid, the receptors acetate binds, the acetyl-CoA it becomes, and the acetyl groups that reach histones (2026-09-21) · lines 303–314

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transgenic monomeric red fluorescent protein reporter mice with FACS purification and quantitative PCR · source_derived_draft · unverified_draft

### acetate-ffar2-mostly-leukocytes The FFAR2 reporter was strongly expressed in a large population of leukocytes in the lamina propria, particularly of the small intestine, but surprisingly only weakly in a subpopulation of enteroendocrine cells; nevertheless synthetic ligands specific for either FFAR3 or FFAR2 each released GLP-1 from colonic crypt cultures. Condition category: normal nutrient_topic: Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. plain_language: FFAR2 turned out to sit mainly on immune cells rather than on the hormone cells, though its agonist still released the hormone. organism: Mouse tissue_or_cell_type: Whole gastrointestinal tract experimental_model: Transgenic monomeric red fluorescent protein reporter mice with FACS purification and quantitative PCR limitations: Reporter expression is not the same as receptor protein. The FFAR2 result here is weaker in enteroendocrine cells than the rat immunohistochemistry in this collection reports. exposure: Cell-type resolved expression of FFAR2 and FFAR3 reporters, with receptor-specific synthetic agonists on colonic crypt cultures evidence_span: {"source_cache": "artifacts/acetate-research/23885020.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b834455e11c2b8fa3c4c19c5d01375815e46c3b0f8e25eb184f0eaa6a51c749e", "start_char": 0, "end_char": 2144, "text_sha256": "b834455e11c2b8fa3c4c19c5d01375815e46c3b0f8e25eb184f0eaa6a51c749e"} [acetate-p23885020] GPR41/FFAR3 and GPR43/FFAR2 as cosensors for short-chain fatty acids in enteroendocrine cells vs FFAR3 in enteric neurons and FFAR2 in enteric leukocytes. (2013). https://pubmed.ncbi.nlm.nih.gov/23885020/ DOI: 10.1210/en.2013-1142