Expression of Neurotensin and Its Receptors Along the Intestinal Tract in Type 2 Diabetes Patients and Healthy Controls
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Expression of Neurotensin and Its Receptors Along the Intestinal Tract in Type 2 Diabetes Patients and Healthy Controls. / Gilliam-Vigh, Hannah; Jorsal, Tina; Nielsen, Sophie W.; Forman, Julie L.; Pedersen, Jens; Poulsen, Steen S.; Vilsbøll, Tina; Knop, Filip K.
I: Journal of Clinical Endocrinology & Metabolism, 2023, s. 2211–2216.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Expression of Neurotensin and Its Receptors 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.
PY - 2023
Y1 - 2023
N2 - Context Enteroendocrine N cells secrete neurotensin (NTS). NTS reduces food intake in rodents and may increase insulin release. In humans, postprandial NTS responses increase following Roux-en-Y gastric bypass, associating the hormone with the glucose- and body weight-lowering effects of these procedures. Objective We looked at N cell density and mucosal messenger RNA (mRNA) expression profiles of NTS and NTS receptors in type 2 diabetes (T2D) patients and healthy controls. Methods Using double-balloon enteroscopy, 12 patients with T2D and 12 sex-, age-, and body mass index-matched healthy controls had mucosa biopsies taken from the entire length of the small intestine (at 30-cm intervals) and from 7 anatomically well-defined locations in the large intestine. Biopsies were analyzed using immunohistochemistry and mRNA sequencing. Results N cell density and NTS mRNA expression gradually increased from the duodenum to the ileum, while negligible NTS-positive cells and NTS mRNA expression were observed in the large intestine. NTS receptor 1 and 2 mRNA expression were not detected, but sortilin, a single-pass transmembrane neuropeptide receptor of which NTS also is a ligand, was uniformly expressed in the intestines. Patients with T2D exhibited lower levels of NTS-positive cells and mRNA expression than healthy controls, but this was not statistically significant after adjusting for multiple testing. Conclusion This unique intestinal mapping of N cell density and NTS expression shows increasing levels from the small intestine's proximal to distal end (without differences between patients with T2D and healthy controls), while negligible N-cells and NTS mRNA expression were observed in the large intestine. Sortilin was expressed throughout the intestines in both groups; no NTS receptor 1 or 2 mRNA expression were detected.
AB - Context Enteroendocrine N cells secrete neurotensin (NTS). NTS reduces food intake in rodents and may increase insulin release. In humans, postprandial NTS responses increase following Roux-en-Y gastric bypass, associating the hormone with the glucose- and body weight-lowering effects of these procedures. Objective We looked at N cell density and mucosal messenger RNA (mRNA) expression profiles of NTS and NTS receptors in type 2 diabetes (T2D) patients and healthy controls. Methods Using double-balloon enteroscopy, 12 patients with T2D and 12 sex-, age-, and body mass index-matched healthy controls had mucosa biopsies taken from the entire length of the small intestine (at 30-cm intervals) and from 7 anatomically well-defined locations in the large intestine. Biopsies were analyzed using immunohistochemistry and mRNA sequencing. Results N cell density and NTS mRNA expression gradually increased from the duodenum to the ileum, while negligible NTS-positive cells and NTS mRNA expression were observed in the large intestine. NTS receptor 1 and 2 mRNA expression were not detected, but sortilin, a single-pass transmembrane neuropeptide receptor of which NTS also is a ligand, was uniformly expressed in the intestines. Patients with T2D exhibited lower levels of NTS-positive cells and mRNA expression than healthy controls, but this was not statistically significant after adjusting for multiple testing. Conclusion This unique intestinal mapping of N cell density and NTS expression shows increasing levels from the small intestine's proximal to distal end (without differences between patients with T2D and healthy controls), while negligible N-cells and NTS mRNA expression were observed in the large intestine. Sortilin was expressed throughout the intestines in both groups; no NTS receptor 1 or 2 mRNA expression were detected.
KW - enteroendocrine cells
KW - neurotensin (NTS)
KW - immunohistochemistry
KW - mRNA expression
KW - type 2 diabetes
KW - GASTRIC BYPASS
KW - GLUCAGON
KW - SOMATOSTATIN
KW - RELEASE
KW - INSULIN
KW - GENE
U2 - 10.1210/clinem/dgad146
DO - 10.1210/clinem/dgad146
M3 - Journal article
C2 - 36916883
SP - 2211
EP - 2216
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
ER -
ID: 342925248