Duodenal neuroendocrine cells and neuromedin U in subjects with obesity: Relationship with type 2 diabetes and glucose homeostasis

• Published in: Physiological reports Vol. 13; no. 15; pp. e70489 - n/a
• Main Authors: Bur, Hassan, Hukkanen, Janne, Savolainen, Markku J., Koivukangas, Vesa, Karttunen, Tuomo J.
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.08.2025; John Wiley and Sons Inc; Wiley
• Subjects: Adult; Biopsy; Blood Glucose - metabolism; Body mass index; Cells; chromogranin A; Chromogranin A - metabolism; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; duodenum; Duodenum - metabolism; Duodenum - pathology; Female; Gastrointestinal surgery; GLP‐1; Glucagon; Glucagon-Like Peptide 1 - metabolism; Glucose; Homeostasis; Humans; Hyperplasia; Insulin; Lamina propria; Male; Metabolism; Middle Aged; neuroendocrine; Neuroendocrine Cells - metabolism; Neuromedin; neuromedin U; Neuropeptides - metabolism; Obesity; Obesity - metabolism; Obesity - pathology; Original; Regular Manuscript; Roles; Serotonin; Serotonin - metabolism; Small intestine; serotonin; neuroendocrine; type 2 diabetes; neuromedin U; chromogranin A; GLP‐1; duodenum; obesity
• ISSN: 2051-817X; 2051-817X
• DOI: 10.14814/phy2.70489

Duodenal endocrine cells contribute to the incretin response, yet their changes in obesity and type 2 diabetes (T2D) remain controversial. We quantified expression of chromogranin A, glucagon‐like peptide‐1 (GLP‐1), serotonin, and neuromedin U (NmU) in duodenal biopsies from 34 participants with obesity (19 with T2D, 15 without) and six healthy controls. Compared to controls, the patients with obesity showed significantly higher proportions of chromogranin A ( p = 0.007), GLP‐1 ( p = 0.006), and serotonin ( p = 0.013) expressing cells, irrespective of T2D status. GLP‐1 expression correlated with HbA1C ( r = 0.454, p = 0.005) and meal test glucose ( r = 0.455, p = 0.0018) but not with insulin. Chromogranin A expression correlated with both GLP‐1 ( r = 0.486, p = 0.003) and serotonin ( r = 0.475, p = 0.003), as well as BMI ( r = 0.429, p = 0.007). NmU was detected in the lamina propria but did not differ among groups. For NmU, an association with insulin (incremental AUC, r = 0.363, p = 0.045) was observed. In conclusion, obesity was associated with hyperplasia of duodenal GLP‐1, serotonin, and chromogranin A cells. The link between GLP‐1 expression, HbA1C, and meal test glucose indicates that, despite increased numbers of GLP‐1–producing cells, individuals with obesity may still experience insufficient incretin action. No evidence supported a role for NmU as a human decretin in these patients.