Glucagon-like peptide (GLP)-1 inhibits acid secretion and gastric emptying in humans, but the effect on acid secretion is lost after vagotomy. To elucidate the mechanism involved, we studied its effect on vagally stimulated gastropancreatic secretion and motility in urethan-anesthetized pigs with cut splanchnic nerves, in which insulin-induced hypoglycemia elicited a marked stimulation of gastropancreatic secretion and antral motility. In addition, we studied vagally stimulated motility and pancreatic secretion in isolated perfused preparations of the porcine antrum and pancreas. GLP-1 infusion (2 pmol ⋅ kg−1 ⋅ min−1) strongly and significantly inhibited hypoglycemia-induced antral motility, gastric acid secretion, pancreatic bicarbonate and protein secretion, and pancreatic polypeptide (PP) secretion. GLP-1 (at 10−10–10−8mol/l) did not inhibit vagally induced antral motility, pancreatic exocrine secretion, or gastrin and PP secretion in isolated perfused antrum and pancreas. We conclude that the inhibitory effect of peripheral GLP-1 on upper gastrointestinal secretion and motility is exerted via interaction with centers in the brain or afferent neural pathways relaying to the vagal motor nuclei.

MicroRNAs have potential as diagnostic cancer biomarkers. The aim of this study was (1) to define microRNA expression patterns in formalin-fixed parafin-embedded tissue from pancreatic ductal adenocarcinoma, ampullary adenocarcinoma, normal pancreas and chronic pancreatitis without using micro-dissection and (2) to discover new diagnostic microRNAs and combinations of microRNAs in cancer tissue. The expression of 664 microRNAs in tissue from 170 pancreatic adenocarcinomas and 107 ampullary adenocarcinomas were analyzed using a commercial microRNA assay. Results were compared with chronic pancreatitis, normal pancreas and duodenal adenocarcinoma. In all, 43 microRNAs had higher and 41 microRNAs reduced expression in pancreatic cancer compared with normal pancreas. In all, 32 microRNAs were differently expressed in pancreatic adenocarcinoma compared with chronic pancreatitis (17 higher; 15 reduced). Several of these microRNAs have not before been related to diagnosis of pancreatic cancer (eg, miR-492, miR-614, miR-622). MiR-614, miR-492, miR-622, miR-135b* and miR-196 were most differently expressed. MicroRNA profiles of pancreatic and ampullary adenocarcinomas were correlated (0.990). MicroRNA expression profiles for pancreatic cancer described in the literature were consistent with our findings, and the microRNA profile for pancreatic adenocarcinoma (miR-196b-miR-217) was validated. We identified a more significant expression profile, the difference between miR-411 and miR-198 (P ¼ 2.06 Â 10 À 54 ) and a diagnostic LASSO classifier using 19 microRNAs (sensitivity 98.5%; positive predictive value 97.8%; accuracy 97.0%). We also identified microRNA profiles to subclassify ampullary adenocarcinomas into pancreatobiliary or intestinal type. In conclusion, we found that combinations of two microRNAs could roughly separate neoplastic from nonneoplastic samples. A diagnostic 19 microRNA classifier was constructed which without micro-dissection could discriminate pancreatic and ampullary adenocarcinomas from chronic pancreatitis and normal pancreas with high sensitivity and accuracy. Ongoing prospective studies will evaluate if these microRNA profiles are useful on fine-needle biopsies for early diagnosis of pancreatic cancer. Modern Pathology (2012Pathology ( ) 25, 1609Pathology ( -1622 doi:10.1038/modpathol.2012; published online 10 August 2012Keywords: ampullary adenocarcinoma; chronic pancreatitis; microRNA; normal pancreas; pancreatic adenocarcinoma; pancreatic cancer Pancreatic cancer is the fourth most common cause of cancer death in United States and Europe. 1,2 Less than 20% of the patients can be operated with curative intent and the 5-year survival after surgery is below 20%. 3 Early diagnosis is difficult and the clinical and histological similarities between pancreatic cancer and chronic pancreatitis further complicate the differentiation between inflammation and cancer.

Background-Glucagon-like peptide-1 (GLP-1) (7-36) amide is an intestinal incretin hormone which also inhibits gastric acid secretion in humans. Its mechanism of action is unclear, but it strongly inhibits vagaily induced secretion (sham feeding), suggesting that it could influence vagal activity. Aim/Methods-The effect of intravenous GLP-1 (7-36 amide) (1 pmollkg/min) was studied on pentagastrin induced acid secretion in otherwise healthy subjects, previously vagotomised for duodenal ulcer (n=8) and in a group of young (n=8) and old (n=6) healthy volunteers. Results-Pentagastrin increased acid secretion significantly in all three groups, but the plateau concentration in the vagotomised subjects was lower than in controls. Infusion of GLP-1 (7-36 amide) significantly inhibited acid secretion in the control groups (to 67 (SEM 6) and 74 (SEM 3)% of plateau concentrations in young and old controls, respectively) but had no effect in the vagotomised subjects. Differences in plasma concentrations of GLP-1 (7-36 amide), recovery of gastric marker, duodenal regurgitation, or Helicobacter pylorn status could not explain the lack of effect. Blood glucose was lowered equally by GLP-1 (7-36 amide) in all subjects. Conclusion-The inhibitory effect of GLP-1 (7-36 amide) on acid secretion depends on intact vagal innervation of the stomach. (Gut 1997; 40: 597-601) Keywords: ileal brake, enterogastrone, vagotomy, pentagastrin, proglucagon.Glucagon-like peptide-1 (GLP-1) (7-36 amide) is a peptide processed from proglucagon in open type endocrine cells (L cells) in the small intestine and colon,'-5 from which it is released into the circulation in response to feeding.3 9It has attracted considerable interest because of its potent insulinotropic and glucagonostatic effects, whereby it lowers blood glucose. Because of this it has been proposed as a therapeutic agent in the treatment of type 2 diabetes mellitus.1l-5 In addition to its glucoregulatory effects GLP-1 (7-36 amide) strongly inhibits gastrointestinal motility and secretion including meal and pentagastrin stimulated acid secretion.'1'8 It has, therefore, been suggested to act as an important enterogastrone in humans.""'5It is not clear by what mechanism(s) GLP-1 (7-36 amide) inhibits acid secretion in humans. Conceivably, it might act locally by inhibiting parietal cell secretion directly or indirectly via a paracrine action of an increased release of somatostatin. It might also act by inhibiting vagal transmission to the parietal cells at the gastric level or by inhibiting vagal efferent activity via a central mechanism. Recent experiments in our laboratory have shown that GLP-1 (7-36 amide) in physiological concentrations almost abolished acid secretion induced by sham feeding, indicating that GLP-1 (7-36 amide) effectively also inhibits neurally induced acid secretion.19To determine whether the inhibitory effect of GLP-1 (7-36 amide) on acid secretion is exerted at the gastric level or whether it involves mainly neural mechanisms we have investigated its effec...

The combination of five miRNAs expression in non micro-dissected FFPE PC tissue can identify patients with short OS after radical surgery. The results are independent of chemotherapy treatment. Patients with a prognostic index > median had a very short median OS of only 1 year.