Chronic pancreatitis and diabetes mellitus: Plasma and gastroduodenal mucosal profiles of regulatory peptides (gastrin, motilin, secretin, cholecystokinin, gastric inhibitory polypeptide, somatostatin, VIP, substance P, pancreatic polypeptide, glucagon, enteroglucagon, neurotensin)

A disturbed intraduodenal milieu and pancreatic scarring in advanced chronic pancreatitis (CP) may lead to changes of gut and pancreatic hormones. In the present study, the gastroduodenal mucosal content of several regulatory peptides was determined in 8 patients with severe calcific CP and 8 healthy volunteers. In addition, hormone release into the bloodstream was estimated after intraduodenal acid/glucose stimulation in the control subjects and 8 CP patients each with or without secondary diabetes mellitus (DM), and in 8 patients with juvenile DM, so that disturbed gut hormone release could be attributed either to CP or DM. While VIP release into the circulation was similar in all participants, mucosal levels of VIP and substance P were significantly elevated in the duodenal bulb and descending duodenum of CP patients. The somatostatin content of gastroduodenal mucosa in CP was at least as high as in normals. Gastrin was significantly more abundant only in the duodenal bulb of CP patients, while plasma gastrin was normal. Duodenal CCK concentrations tended to be elevated in the duodenal bulb, but not significantly. The release of secretin seemed to be higher in type-1 diabetics than in CP patients. The mucosal pattern of GIP was nearly identical in CP patients and controls. Compatible with this finding, the GIP release did not show any peculiarities in CP with or without DM or in DM. Basal and stimulated plasma levels of motilin were abnormally high in CP. Pancreatic polypeptide plasma levels were normal in DM, but significantly reduced in CP, especially in CP with DM. Fasting PP and stimulated pancreatic enzyme outputs were linearly related. This was not so pertinent to PP release, although it was significantly diminished in CP. Basal plasma glucagon was similar in all groups, including DM, with a significant paradoxical rise in the latter group after intraduodenal glucose. While basal plasma enteroglucagon concentrations did not differ between the 4 goups, the integrated response tended to be elevated in CP with DM. With neurotensin, the enhanced release was even significant in CP with DM. In conclusion, especially in advanced CP, namely CP with DM, mucosal enrichment with VIP and substance P in the proximal duodenum may represent a reactive phenomenon. Among the plasma hormones measured, fasting PP levels appear to mirror pancreatic exocrine insufficiency better than other hormone abnormalities and might have some diagnostic relevance. Enhanced release of enteroglucagon and neurotensin might also give some idea of the degree of maldigestion.