Insulin-Induced Hypoglycemia Stimulates Gastric Vagal Activity and Motor Function without Increasing Cardiac Vagal Activity

Abstract

Background/Aims: We investigated whether increasing the efferent vagal activity by insulin-induced hypoglycemia would enhance gastric emptying and volumes in healthy subjects. Methods: Twenty healthy volunteers (10 males) were examined with and without vagal stimulation by insulin-induced hypoglycemia using a glucose clamp technique. Stomach function was tested by drinking meat soup (0.04 kcal ml^–1) at a rate of 100 ml min^–1 until maximal capacity. Intragastric volume at maximal drinking capacity was determined by three-dimensional ultrasound. Respiratory sinus arrhythmia (RSA) was used as an index of cardiac vagal activity and plasma pancreatic polypeptide (PP) as a measure of gastric vagal activity, and skin conductance (SC) as a measure of sympathetic tone. Results: Insulin-induced hypoglycaemia increased drinking capacity (p = 0.002), gastric emptying (p = 0.02), PP (p = 0.004) and SC (p = 0.004), while intragastric volume was unchanged (p = 0.7) and RSA decreased (p = 0.03). Conclusion: Enhancement of gastric vagal activity by insulin-induced hypoglycemia increased drinking capacity and gastric emptying similarly, resulting in an unchanged intragastric volume. Enhanced efferent vagal activity to the stomach (as measured by PP) was not associated by enhanced cardiac vagal activity (as measured by RSA), possibly a consequence of stress-induced sympathetic activation during the procedure.

Distension‐induced gastric accommodation in functional dyspepsia: effect of autonomic manipulation

“…31 However, disturbed cardiac vagal function is not necessarily closely related to gastric vagal or motor function. 32 Because of the dual vagal control of gastric tone, 25,26,33 increased cholinergic input to the proximal stomach agrees with disturbed vagal function, and hence is in accordance with previous findings. Increased cholinergic tone could be due to temporary or permanent autonomic or enteric nervous system dysfunction, which might be the target of therapeutic intervention.…”

“…Functional dyspepsia has been associated with disturbed vagal function, demonstrated both as diminished heart rate variability 7,30 and disturbed responsiveness to cardiac vagal tests, 6 as well as reduced response of serum level of pancreatic polypeptide to insulin‐induced hypoglycaemia 31 . However, disturbed cardiac vagal function is not necessarily closely related to gastric vagal or motor function 32 . Because of the dual vagal control of gastric tone, 25,26,33 increased cholinergic input to the proximal stomach agrees with disturbed vagal function, and hence is in accordance with previous findings.…”

Insulin reduces excitation in gastric-related neurons of the dorsal motor nucleus of the vagus

“…Additionally, insulin injected directly into the NTS of anesthetized rats produces depressor and bradycardic effects, which are dependent on PI3K (25). While insulin-induced hypoglycemia enhances vagal activity (24), hyperglycemia depresses vagal tone (31). Therefore, insulin appears to act in the dorsal vagal complex to potentially decrease gastric tone.…”

“…Disruption of a central insulin receptor gene results in obesity, hyperphagia, hyperinsulinemia, insulin resistance, and hypertriglyceridemia (1,8,33). Insulin-induced hypoglycemia enhances vagal activity (24), while hyperglycemia depresses vagal tone (31). Eliminating or blocking components of the insulin receptor pathway centrally, such as phosphatidylinositol 3 kinase (PI3K) or the ATP-dependent K ϩ (i.e., K ATP ) channel, disrupts vagal control of energy homeostasis (36,37), and insulin applied centrally improves hepatic gluconeogenesis in models of diabetes in a vagally mediated manner (29,33,34).…”

Varying postprandial abdominovagal and cardiovagal activity in normal subjects

“…Conversely, a relatively weak correlation between disordered motility and abnormal cardiovascular autonomic function (either parasympathetic or sympathetic) has also been reported 10 . Due to the regionality of ANS, 11 different responses among different organ systems to the same stimulations (such as a meal) are quite possible.…”