Hyperglycemia Reduces Gastric Secretory and Plasma Pancreatic Polypeptide Responses to Modified Sham Feeding in Humans

Abstract

We have investigated the effect of acute stable hyperglycemia on gastric acid secretion and serum gastrin and pancreatic polypeptide (PP) release. Gastric acid output was measured under basal conditions and in response to modified sham feeding (MSF) in 7 healthy volunteers on two separate occasions: during normoglycemia (serum glucose 5 mmol/l) and during hyperglycemia (serum glucose 15 mmol/l). PP secretion was determined as an indirect measure of vagal-cholinergic tone. Basal acid output during hyperglycemia (4.7 ± 1.0 mmol/h) was not significantly different from euglycemia (5.4 ± 0.6 mmol/h), but MSF-stimulated acid output during hyperglycemia (14.7 ± 3.3 mmol/90 min) was significantly (p < 0.05) reduced compared to euglycemia (24.7 ± 3.2 mmol/90 min). Serum gastrin levels were not affected by MSF. During hyperglycemia, the integrated PP secretion in response to MSF (235 ± 95 pmol/l · 90 min) was significantly (p < 0.05) reduced compared to euglycemia (434 ± 71 pmol/l · 90 min). This study indicates that (1) serum glucose affects cephalic-stimulated gastric acid secretion, and (2) PP secretion after MSF is significantly reduced during hyperglycemia suggesting impaired vagal-cholinergic activity during hyperglycemia.

Prevalence of Delayed Gastric Emptying in Diabetic Patients and Relationship to Dyspeptic Symptoms

“…The delay in gastric emptying observed in our studies is most likely due to reversible or irreversible autonomic dysfunction at the level of the extrinsic nervous system and/or the myenteric plexus (25)(26)(27). Without doubt, the actual blood glucose concentration plays an important role in reversible autonomic dysfunction because it has been shown that blood glucose concentration affects vagal tone and blunt gastrocolonic reflexes (28,29).…”

Relationships of Upper Gastrointestinal Motor and Sensory Function With Glycemic Control

“…In addition to its effects on motor function, acute hyperglycemia also affects upper gastrointestinal exocrine secretory function, with suppression of gastrin, gastric acid, and pancreatic exocrine secretion in healthy subjects (66)(67)(68).…”

“…In healthy subjects, the secretion of pancreatic polypeptide, which is under vagal cholinergic control, is diminished during acute hyperglycemia in healthy control subjects, suggesting a reversible impairment of vagal efferent function (67). The reduced heart rate response to standing (30:15 ratio) in healthy volunteers during hyperglycemia when compared with euglycemia is also indicative of impairment of vagal parasympathetic function (79).…”

Neuronal activation of brain vagal-regulatory pathways and upper gut enteric plexuses by insulin hypoglycemia

“…The involvement of upper GI tract organs in the hyperglycemia-induced delay of gastric emptying (5) corresponds to the distribution of the vagus in the GI tract (52). GI functions that are well established to be stimulated by vagal efferent activation, such as sham feeding-induced gastric acid secretion and pancreatic polypeptide release from the pancreas, were remarkably reduced during hyperglycemia (34). In contrast to hyperglycemia, insulin hypoglycemia is well established as a central vagal stimulus on upper GI functions (63,64,67).…”