Distribution of Somatostatin and Its Receptors in the Intestinal Tract in Healthy Patients and Patients with Type 2 Diabetes.

Abstract

Somatostatin is a peptide hormone exerting actions through 5 different somatostatin receptors (SSTR1-5). Somatostatin-positive cells have previously been found in intestinal mucosa and may be implicated in the pathophysiology of type 2 diabetes. Here, we characterized the distribution of somatostatin-positive cells and the mRNA expression profiles of somatostatin and SSTR1-5 along the intestinal tract of healthy individuals and patients with type 2 diabetes. Mucosal biopsies were collected using double-balloon enteroscopy along the entire small intestine (with 30 cm intervals) and from 7 anatomically well-defined regions in the duodenum, at the Treitz ligament, at the ileocecal transition, and in the large intestine. Samples were collected from 12 patients with type 2 diabetes and 12 age- and body mass index-matched nondiabetic individuals. The biopsies were analyzed for somatostatin and mRNA sequencing of somatostatin and SSTR1-5. Somatostatin-positive mucosal cells were found throughout the intestinal tract in both groups with the highest density of cells in the proximal part of the small intestine and in the rectum, corresponding well with somatostatin mRNA expression profiles. SSTR1 was abundantly expressed with decreasing levels of mRNA along the small intestine and uniform, low expression through the large intestine. We detected low levels of SSTR2, SSTR3, and SSTR5 mRNA and no SSTR4 mRNA along the intestinal tract in both groups with no significant differences between groups for cell density or mRNA expression. Somatostatin-positive cells as well as somatostatin and SSTR1 mRNA expression are abundant in the mucosa through the entire human intestinal tract, and no differences between healthy individuals and patients with type 2 diabetes were observed. mRNA expression levels of SSTR2-5 are low and SSTR4 undetectable in the human intestinal tract.