title: Reduced GLP-1R expression in gastric glands of patients with type 2 diabetes mellitus.
abstract: BACKGROUND
  The incretin effect is reduced in type 2 diabetes mellitus (T2DM) patients. Whether the impaired function of the enteropancreatic axis in these patients is due to defective GLP-1 receptor (GLP-1R) expression in extrapancreatic target organs is not known.
  
  
  OBJECTIVE
  To compare the GLP-1R expression and distribution in gastric mucosa biopsies of patients with (n =22) and without (n =22) T2DM referred for routine esophagogastroduodenoscopies. GLP-1R mRNA levels were estimated by real-time PCR. The intensity of GLP-1R immunostaining, frequency, and types of glandular cells bearing GLP-1R and their glandular distribution in different stomach mucosa regions were evaluated by immunohistochemical morphological semiquantitative and quantitative analysis.
  
  
  RESULTS
  Mean mRNA GLP-1R levels were significantly reduced in patients with T2DM compared with nondiabetic patients (P < .02). Immunohistochemical analysis revealed that the reduced GLP-1R expression in T2DM patients was due to a decreased intensity of immunostaining (P < .01). The number of glandular GLP-1R-bearing cells in both body and antrum mucosa was decreased in T2DM patients. Most notably, the frequency of GLP-1R immunoreactive acid-secreting parietal cells was reduced in the neck area of the gastric principal glands of T2DM patients (P < .01). No correlation was found between the reduced GLP-1R expression and clinical parameters including body mass index, age, glycosylated hemoglobin, and disease duration.
  
  
  CONCLUSIONS
  This is the first evidence of reduced GLP-1R expression in gastric glands of T2DM patients. These data demonstrate that the defective function of the incretin axis in T2DM may also result from decreased GLP-1R expression in its extrapancreatic target organs.
authors.affiliation: Institute of Gastroenterology (E.B., G.B.-Y., H.S.), Diabetes and Immunology Research Laboratory (O.B, M.J.R.), and Department of Internal Medicine "C" (D.C., M.J.R), Assaf Harofeh Medical Center, Zerifin 70300, Israel; and Sackler Faculty of Medicine Tel Aviv University (E.B., O.B., G.B.-Y., D.C., H.S., M.J.R., Tel Aviv 69978, Israel.
authors.forename: E
authors.initials: E
authors.lastname: Broide
authors.forename: O
authors.initials: O
authors.lastname: Bloch
authors.forename: G
authors.initials: G
authors.lastname: Ben-Yehudah
authors.forename: D
authors.initials: D
authors.lastname: Cantrell
authors.forename: H
authors.initials: H
authors.lastname: Shirin
authors.forename: M J
authors.initials: MJ
authors.lastname: Rapoport
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism*; D016145:Endoscopy, Digestive System; D019858:Enteroendocrine Cells / Q000166:cytology / Q000502:physiology; D005260:Female; D005753:Gastric Mucosa / Q000166:cytology / Q000502:physiology*; D005786:Gene Expression Regulation; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D008297:Male; D008875:Middle Aged; D010295:Parietal Cells, Gastric / Q000166:cytology / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D018027:Receptors, Glucagon / Q000235:genetics* / Q000378:metabolism*
chemical_list: C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D012333:RNA, Messenger; D018027:Receptors, Glucagon