Increase In Pancreatic Polypeptide Concentrations Research Articles

Is pancreatic polypeptide response to food ingestion a reliable index of vagal function in type 1 diabetes?

Objective. The diagnosis of autonomic neuropathy in diabetic patients is based on cardiovascular reflex tests. Since cardiac function may be affected by arteriosclerosis and cardiomyopathy in type 1 diabetes mellitus, alternative tests reflecting vagal nerve function, in other organ systems, are needed. In this study the pancreatic polypeptide (PP) response to a mixed meal was evaluated in healthy subjects and in recently diagnosed type 1 diabetic patients. Material and methods. The PP response was studied at different levels of the vagally mediated reflex arch by application of different stimuli: meal ingestion, i.v. edrophonium (a cholinesterase inhibitor) injection and arginine infusion. Results. Meal ingestion (stimulation of cerebral/vagal level) resulted in a significant and similar PP response in the two groups; i.v. edrophonium injection (stimulating at the second neuron level) resulted in a smaller increase in PP concentrations in the type 1 diabetic patients as compared with the healthy subjects, whereas direct PP‐cell stimulation by arginine infusion resulted in similar increments in PP concentrations in the two groups. Thus, in recently diagnosed type 1 diabetic patients with no known manifestations of diabetic neuropathy, the cholinergic second neuron function of the vagal arch to the pancreas is impaired, whereas intrinsic PP‐cell function is unaffected. Conclusions. This abnormality in cholinergic second neuron function of the vagal reflex arch and the fact that three of the healthy subjects had no increase in PP concentrations at all during the meal test indicates that PP response to a mixed meal is unsuitable for the diagnosis of autonomic neuropathy in type 1 diabetes. The nature of the defect in the second neuron of the vagal innervation of the pancreas in type 1 diabetes remains to be elucidated.

Impaired interdigestive pancreatic polypeptide release. Early hormonal disorder in chronic pancreatitis?

The purpose of this study was to investigate interdigestive cycling and postprandial release of pancreatic polypeptide (PP) in relation to exocrine pancreatic function in chronic pancreatitis (CP). We investigated nine patients with mild-moderate CP (MCP), eight patients with severe CP and steathorrea (SCP), and 17 healthy subjects as controls. Interdigestive antroduodenal motility was monitored by means of manometry. Following two consecutive motility cycles, a standard test meal was administered. Plasma samples were drawn for PP determinations every 15 min throughout the entire study, which concluded 2 hr after ingestion of the meal. Mean interdigestive PP plasma concentrations during phase III motor activity were lower in MCP (146 +/- 46 pg/ml) than in controls (270 +/- 42 pg/ml) and lower still in SCP (55 +/- 8 pg/ml). Accordingly, the percent increase in PP concentrations during phase III over those in phase I was progressively decreased from controls (112%) to MCP (62%) to SCP (19%). Mean interdigestive PP concentrations were also lower during phase I and II in SCP than in controls or MCP. None of the postprandial parameters for PP release was affected in the early stage of disease, while mean, peak, and integrated postprandial values were significantly lower in SCP than in controls or MCP. Thus, we observed a progressive diminution of both interdigestive and postprandial PP release with increasing severity of disease. Interdigestive release parameters, in particular, were tightly correlated with exocrine function. CP appears to alter interdigestive PP release to a greater extent than postprandial PP release; this effect is already apparent in early stages of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Impaired pancreatic polypeptide response to a meal in type 1 diabetic patients: vagal neuropathy or islet cell dysfunction?

The pancreatic polypeptide (PP) response to a mixed meal was investigated in seven insulin-dependent diabetics without measurable signs of diabetic autonomic neuropathy, and in seven healthy subjects. Since acute changes in metabolic regulation might influence the meal-induced PP response, the insulin-dependent diabetic patients were studied during normo- and hyperglycemic experimental conditions at blood glucose levels of 5 and 15 mmol/l, respectively. The PP response was identical on the two occasions, the response being significantly smaller than in the healthy subjects. Thus, PP response is independent of short-term changes in metabolic control. Since the response was attenuated in the insulin-dependent diabetic patients, who had no otherwise measurable signs of neuropathy, the PP response to a meal could be a sensitive indicator of dysfunction of the reflex arc controlling PP secretion in insulin-dependent diabetic patients. Alternatively, the reduction in PP secretion in these patients reflects dysfunction of the PP secreting cells of the pancreas. Iv injection of cholecystokinin-8 elicited a small but significant increase in PP concentrations, while iv secretin did not increase PP concentrations at all in healthy subjects. These stimuli are therefore less suitable in the assessment of vagal neuropathy.

Pancreatic polypeptide secretion before and after gastric bypass surgery for morbid obesity.

Basal, meal-stimulated, and insulin-stimulated secretion of pancreatic polypeptide (PP) has been measured before and 3 and 12 months after gastric bypass surgery in 10 obese patients. The basal serum concentration of PP was significantly reduced after the operation. After a meal there was a significant increase in PP concentration both before and after operation. The early phase of meal-stimulated PP release was similar before and 12 months after surgery, but during the late phase the concentrations were 30% lower after the operation than preoperative values. Insulin-stimulated PP release was significantly reduced postoperatively. It is concluded that both basal and stimulated secretion of PP is significantly affected by gastric bypass surgery. The results indicate that the distal part of the stomach and the duodenum play no role in the early phase of meal-stimulated PP release and a minor role in the late phase of meal-stimulated PP release. The reduced basal level of PP and reduced PP response to insulin postoperatively indicate that gastric bypass surgery leads to impaired secretion of PP from the pancreas.