R
1
2
3
4
5
6
7
8
9
10
Ingenuity analysis of exendin-4 treated Brunner’s glands
p-value Ingenuity analysis of exendin-4 treated Islets
p-value
eNOS Signaling 5.16E-05 Telomerase Signaling 6.67E-05 Acute Myeloid Leukemia
Signaling
2.85E-04 Thrombin Signaling 1.21E-02
Small Cell Lung Cancer Signaling
1.04E-03 Telomere Extension by Telomerase
1.36E-02
EGF Signaling 1.35E-03 Phospholipase C Signaling 1.59E-02 p53 Signaling 1.66E-03 Huntington's Disease
Signaling
1.76E-02
Study number, age, sex and strain
liraglutide dose and time (n)
Vehicle, time, (n)
Non dosed , (n)
Time series 21, 12 weeks, male, C57BI/6J
0.5mg/kg, 2h (3), 6h (3), 12h (3) or 18h (3)
2h (3) 0h (3)
6 hours 24, 12 weeks, male, C57BI/6J
0.5mg/kg, 6h (12)
6h (12)
7 days 24, 12 weeks, male, C57BI/6J
1.0mg/kg, 7days (12)
7 days (12)
Score Severity of lesions Hyperplasia Crypt damage Area involved
0 Normal Normal Normal 0-10%
1 Mild lesions were
small. focal. or widely separated multifocal areas of inflammation
limited to the lamina propria.
Mild hyperplasia consisted of morphologically
normal lining epithelium that was up to one time thicker (length of crypts) than adjacent or control
mucosa.
Mild crypt damage consisted of damage of basal 2/3 with focal crypt loss and intact surface epithelium.
10-40%
2 Moderate lesions were either multifocal or represented by locally extensive
areas of inflammation
extending into the submucosa.
Moderate
hyperplasia was characterized by the lining epithelium being above two to three times normal thickness. cells were
hyperchromatic with mitotic figures.
Moderate crypt damage consisted of damage of basal 2/3 with focal crypt loss and intact surface epithelium.
40-70%
3 Severe lesions
with extensive diffuse infiltration with inflammatory cells involving tunica mucosa.
submucosa and potentially
muscularis.
Severe hyperplastic regions exhibited markedly thickened epithelium (three or more times normal).
marked
hyperchromasia of cells. few to no goblet cells and a high mitotic index of cells within the crypts
Severe crypt damage
consisted of multifocal crypt loss
with intact surface epithelium or focal crypt loss with no surface epithelium (erosion/ulceration)
>70%
Rectum sigmoideum Desendense transversum Asendense Coecum Ilium Duodenum
Control 14 12 13 12 12 7 5 15
CD 4 4 6 6 5 3 10 1
CD (Inflamed)
3 6 5 6 3 3 7 0
UC 4 17 13 5 3 2 7 1
UC (Inflamed)
14 18 2 2 2 0 0 0
Applied biosystems ID gene name
Species gene of interest (GOI)
Mm00466391_m1 MUC5B Mouse GOI
Mn00445292 GLP-1R Mouse GOI
Mm00505402_m1 IL-33 Mouse GOI
Mm01268754_m1 CCL20 Mouse GOI
Mm01192943_m1 Il-22ra Mouse GOI
Hs9999901_s1 18s rRNA human HK
Applied biosystems ID gene name
Species gene of interest (GOI)
hs00861595_m1 MUC5B human GOI Hs 00157705_m1 GLP-1R human GOI Hs 00369211_m1 IL-33 human GOI
hs00222035_m1 IL-22RA human GOI hs00899658_m1 MMP1 human GOI
hs01011368_m1 CCL20 human GOI hs9999907_m1 B2M human HK
hs9999910_m1 TBP human HK
hs9999903_m1 ACTB human HK
Hs 0494521_s1 PPIA human HK
