TY - JOUR

T1 - Expression of Secretin and its Receptor Along the Intestinal Tract in Type 2 Diabetes Patients and Healthy Controls

AU - Gilliam-Vigh, Hannah

AU - Jorsal, Tina

AU - Nielsen, Sophie W

AU - Forman, Julie L

AU - Pedersen, Jens

AU - Poulsen, Steen S

AU - Vilsbøll, Tina

AU - Knop, Filip K

N1 - © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PY - 2023

Y1 - 2023

N2 - BACKGROUND: The hormone secretin (SCT) is released from intestinal S cells and acts via the SCT receptor (SCTR). Circulating SCT levels increase after Roux-en-Y gastric bypass surgery and have been associated with the massive weight loss and the high remission rates of type 2 diabetes (T2D) linked to these operations. Exogenous SCT was recently shown to reduce ad libitum food intake in healthy volunteers. To understand SCT biology and its potential role in T2D pathophysiology, we examined the intestinal mucosal expression profile of SCT and SCTR and evaluated the density of S cells along the intestinal tract of individuals with T2D and healthy controls.METHODS: Using immunohistochemistry and mRNA sequencing, we analyzed intestinal mucosa biopsies sampled along the small intestine at 30 cm intervals and from seven well-defined anatomical sites along the large intestine (during two sessions of double-balloon enteroscopy) in 12 individuals with T2D and 12 healthy controls.RESULTS: Both groups exhibited a progressive and similar decrease in SCT and SCTR mRNA expression and S cell density along the small intestine, with reductions of 14, 100, and 50 times, respectively, in the ileum compared to the duodenum (used as reference). Negligible amounts of SCTR and SCT mRNA, as well as a low S cell density, were found in the large intestine. No significant differences were observed between the groups.CONCLUSIONS: SCT and SCTR mRNA expression and S cell density were abundant in the duodenum and decreased along the small intestine. Very low SCT and SCTR mRNA levels and S cell numbers were observed in the large intestine; without aberrations in individuals with T2D compared to healthy controls.

AB - BACKGROUND: The hormone secretin (SCT) is released from intestinal S cells and acts via the SCT receptor (SCTR). Circulating SCT levels increase after Roux-en-Y gastric bypass surgery and have been associated with the massive weight loss and the high remission rates of type 2 diabetes (T2D) linked to these operations. Exogenous SCT was recently shown to reduce ad libitum food intake in healthy volunteers. To understand SCT biology and its potential role in T2D pathophysiology, we examined the intestinal mucosal expression profile of SCT and SCTR and evaluated the density of S cells along the intestinal tract of individuals with T2D and healthy controls.METHODS: Using immunohistochemistry and mRNA sequencing, we analyzed intestinal mucosa biopsies sampled along the small intestine at 30 cm intervals and from seven well-defined anatomical sites along the large intestine (during two sessions of double-balloon enteroscopy) in 12 individuals with T2D and 12 healthy controls.RESULTS: Both groups exhibited a progressive and similar decrease in SCT and SCTR mRNA expression and S cell density along the small intestine, with reductions of 14, 100, and 50 times, respectively, in the ileum compared to the duodenum (used as reference). Negligible amounts of SCTR and SCT mRNA, as well as a low S cell density, were found in the large intestine. No significant differences were observed between the groups.CONCLUSIONS: SCT and SCTR mRNA expression and S cell density were abundant in the duodenum and decreased along the small intestine. Very low SCT and SCTR mRNA levels and S cell numbers were observed in the large intestine; without aberrations in individuals with T2D compared to healthy controls.

U2 - 10.1210/clinem/dgad372

DO - 10.1210/clinem/dgad372

M3 - Journal article

C2 - 37335970

VL - 108

SP - e1597–e1602

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 12

ER -