Islet-cell replication, isolated beta-cells, and islet-cell apoptosis.

<p>(A) number of BrdU positive islet cells per 10⁵ cells (N_(BrdU)), (B) total volume of isolated beta-cells (V_(Neo,Pan), (C) number of apoptotic islet cells per 10⁵ cells (N_(Apoptosis)). Open bars: female control mice; filled bars: female GIPR^dn transgenic mice; Data represent means and SEM. * p<0.05 vs. age-matched control; +p<0.05 vs. previous time point.</p

Lipid peroxidation.

<p>Serum malondialdehyde (MDA) levels of GIPR^dn transgenic (tg) and control (co) mice at 45, 90 and 180 days of age. Data represent means and SEM;</p><p>*p<0.05 vs. age-matched control;</p><p>+ p<0.05 vs. previous time point.</p

Representative islet profiles, sampling of sections, counting Q⁻ islets.

<p>Example of an islet profile of a control (A) and a GIPR^dn transgenic mouse (B) immunohistochemically stained for insulin; (C) Sampling scheme for drawing primary and reference sections; (D) Primary section and (E) reference section for counting Q⁻ islets, one Q⁻ may be counted in the example (arrow in E).</p

In vivo insulin secretion studies at 10 days of age.

<p>(A) Blood glucose, (B) serum insulin levels, (C) increase of serum insulin levels from basal levels (fold insulin secretion), (D) serum insulin to pancreatic insulin ratio; Open bars: control mice; filled bars: GIPR^dn transgenic mice; Data represent means and SEM. * p<0.05 vs. age-matched control; + p<0.05 vs. basal values.</p

In vivo investigations.

<p>(A) Randomly fed (10 days) and fasting blood glucose (45-180 days), and (B) randomly fed (10 days) and postprandial serum insulin levels (45–90 days), (C) insulin tolerance test, (D), and area under glucose curve (AUC) during insulin tolerance test shown in C; co, control; tg, GIPR^dn transgenic; Data represent means and SEM, * p<0.05 vs. age-matched control.</p

Quantitative-stereological investigations of the endocrine pancreas.

<p>(A) Total islet volume (V_(Islets,Pan), (B) total beta-cell volume (V_{(B-cells,Islets)}, (C) Number of islets (N_{(Islets, Pan)}, (D) mean islet volume (v_(islets), (E) beta-cell number (N_{(B-cells,Islets)}, (F) mean beta-cell volume (v_(B-cells). Open bars: female control mice; filled bars: female GIPR^dn transgenic mice; Data represent means and SEM. * p<0.05 vs. age-matched control; +p<0.05 vs. previous time point.</p

Apoptosis of HCT116 cells is downregulated after OSM stimulation.

<p>Treatment with OSM (10 ng/mL and 100 ng/mL) for 6 hours significantly reduced caspase-3/7 activity (* p = 0.03; **p = 0.02, respectively) compared to unstimulated HCT116 cells. TNF-α (50 ng/mL) served as positive control (^# p = 0.007 vs. unstimulated HCT116 cells).</p

OSM is up-regulated in colonic biopsies of patients with active inflammatory bowel disease.

<p>OSM expression in colonic biopsies was higher in inflamed colonic biopsy samples in both active CD and UC patients than in non-inflamed colonic lesions of patients in remission. OSM in inflamed lesions is highly expressed in epithelial cells but also in sub-epithelial laminar propria mononuclear cells. Overall, biopsy specimens of 4 CD and 4 UC patients with active disease and in remission were analyzed. Representative images (20× and 40× magnification) of CD patients in remission and active disease (A) and UC patients in remission and active disease (B) and isotype controls are shown. (C) OSM mRNA levels in inflamed mucosal lesions of 23 patients with CD were significant higher than in non-inflamed lesions (*p = 0.001). (D) OSM mRNA levels were not significant different in inflamed lesions compared to non-inflamed lesions of 10 patients with UC (p = 0.11).</p

Rates of mucosal healing in both groups.

<p>In the TNF1 group, 146 patients (72.3%) had no MH, while 56 patients (27.7%) had MH. In the TNF2 group, 13 patients (28.6%) patients had MH, while 33 patients (71.4%) had no MH at follow-up colonoscopy.</p

OSM-mediated wound healing in HCT116 cells is MEK-1- and STAT3-dependent.

<p>Wounding assays were performed to analyze cell migration. Presented are representative images of unstimulated HCT116 cells at baseline (left panel) and after 16 hours (right panel) (A) and OSM-stimulated cells at baseline (left panel) and after 16 hours (right panel) (B). (C) OSM (100 ng/mL) induced a significant increase of cell migration (* p = 3.9×10⁻⁵ vs. unstimulated controls). Preincubation with the MEK-1 inhibitor PD98059 (10 µM) and STAT3 siRNA (5 µM) reduced OSM-induced cell migration in the wounding assay (** p = 1.7×10⁻⁵ and ^# p = 0.01 vs. OSM-stimulated cells). In all experiments, relative cell overgrowth in unstimulated control cells was arbitrarily set to 1.0.</p