Reduced GLP-1R expression in gastric glands of patients with type 2 diabetes mellitus.

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. AIMS AND METHODS: 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. CONCLUSION: 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.

Evidence for aberrant regulation of MAP kinase signal transduction pathway in peripheral blood mononuclear cells in patients with active celiac disease.

BACKGROUND: Aberrant signaling via the p21/mitogen-activated proteins (MAP) kinase pathway has been described in lymphocytes of patients with various autoimmune diseases. There is little published data about the intracellular mediators and signals that regulate expression and activity of transcription factors and their effect on celiac disease induction and progression. AIM: To investigate the possible involvement of MAP kinase pathway in peripheral blood mononuclear cells (PBMC) in celiac disease and its correlation with disease activity. METHODS: Expression of the total and activated forms of two MAP kinases [extracellular response kinase (ERK) and c-Jun amino terminal kinase (JNK)] were studied by Western blots in PBMC of 17 untreated and 19 treated celiac patients, and 17 controls. Seven of these untreated celiac patients were studies before and after 6 months of gluten-free diet. RESULTS: Phosphorylated ERK of active celiac disease patients was significantly lower compared with controls (P < 0.01) and was increased towards normal after 6 month of gluten-free diet (P < 0.01). Phosphorylated JNK was increased significantly in the untreated celiac group (P < 0.01) and normalized towards the control level after 6 months of gluten-free diet (P < 0.04). CONCLUSIONS: Aberrant MAP-kinase pathway activity is associated with active celiac disease (CD). Further studies should examine the potential role of this aberration in pathogenesis of CD.

Impaired temporal contrast sensitivity in dyslexics is specific to retain-and-compare paradigms.

Developmental dyslexia is a specific reading disability that affects 5-10% of the population. Recent studies have suggested that dyslexics may experience a deficit in the visual magnocellular pathway. The most extensively studied prediction deriving from this hypothesis is impaired contrast sensitivity to transient, low-luminance stimuli at low spatial frequencies. However, the findings are inconsistent across studies and even seemingly contradictory. In the present study, we administered several different paradigms for assessing temporal contrast sensitivity, and found both impaired and normal contrast sensitivity within the same group of dyslexic participants. Under sequential presentation, in a temporal forced choice paradigm, dyslexics showed impaired sensitivity to both drifting and flickering gratings. However, under simultaneous presentation, with a spatial forced choice paradigm, dyslexics' sensitivity did not differ from that of the controls. Within each paradigm, dyslexics' sensitivity was poorer at higher temporal frequencies, consistent with the magnocellular hypothesis. These results suggest that a basic perceptual impairment in dyslexics may be their limited ability to retain-and-compare perceptual traces across brief intervals.