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Gut · 2026

Insulin-like peptide 5 is released in response to bile acid in the rectum and is associated with diarrhoea severity in patients with bile acid diarrhoea.

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Bannon Christopher A, Walters Julian R F, Wu Tongzhi, Kay Richard G, Punnoose Austin, Spiller Robin C, Wilson Jonathan, Verdino Petra, Barker Peter, Burling Keith, Horowitz Michael, Rayner Christopher K, Ford Alexander C, Reimann Frank, Gribble Fiona M

Аннотация

BACKGROUND: Insulin-like peptide 5 (INSL5) is an enteroendocrine hormone expressed in distal colonic 'L cells'. Bile acid receptor agonists are known to stimulate INSL5 secretion in primary cell culture, and administration of an INSL5 analogue in animals promotes colonic motility.

OBJECTIVE: This study used a new immunoassay to measure INSL5 in human blood samples, enabling assessment of whether rectal bile acids stimulate INSL5 release in humans and whether INSL5 levels are altered in patients with chronic diarrhoea.

DESIGN: Serum/plasma samples from previously performed studies were used, including healthy volunteers (n=7) who received a rectal enema of taurocholic acid (TCA); fasting and post prandial samples from healthy volunteers (n=10); patients with bile acid diarrhoea (BAD) (n=19) or irritable bowel syndrome with diarrhoea (IBS-D) (n=8); and patients with IBS-D (n=64) treated with ondansetron or placebo.

RESULTS: Rectal TCA but not a control enema promptly elevated plasma INSL5, with the increase in INSL5 correlating negatively with time to, and positively with desire to, defecate post enema. Healthy volunteers had low INSL5 levels (<100 pg/mL), with no change following a mixed meal. Patients with BAD had elevated INSL5 levels, with average stool consistency being positively correlated with serum INSL5 (p<0.001). In people with IBS-D, INSL5 was elevated (>100 pg/mL) in 42%, and this subgroup showed greater improvements in stool consistency with ondansetron therapy (p<0.05).

CONCLUSION: The study highlights that rectal bile acids stimulate INSL5 secretion in humans, and that INSL5 levels are associated with a colonic pro-motility response and pathophysiology of chronic diarrhoea.

Предметные рубрики MeSH

ИП Урсолов Владлен Сергеевич

ИНН 500118482352 · ОГРНИП 314500117700049

Реквизиты и контакты