Dose response relationships of insulin hypoglycaemia and gastric acid in man

Abstract

SUMMARY Fourteen studies of gastric acid secretion in a basal hour and in the two hours after a single intravenous injection of soluble insulin (0.01 to 0.40 units/kg) were performed in a healthy man. The peak acid output after insulin (measured as the two consecutive 15-minute samples giving the highest acid output) was significantly correlated with the lowest concentration of blood glucose, the fall in blood glucose, the rate of fall of blood glucose, and the maximum fall of blood glucose in any 15 minutes. Peak acid outputs after insulin were similar over the range 0.1 to 0.2 units/kg, and greater than at lower or higher doses.These results are contrary to the accepted assumption that insulin-stimulated acid secretion is an 'all-or-none' phenomenon. They support instead the hypothesis that insulin hypoglycaemia provides a quantitative glycopenic stimulus producing quantitative vagal acid response. Extreme hypoglycaemia, below about 15 mg/100 ml of bloodglucose,inhibitsinsulin-stimulated acid secretion.Certain assumptions about the insulin test have been widely held (Roholm, 1930;Hollander, Jemerin, and Weinstein, 1942) in the 40 years since intravenous insulin was found to be an hypoglycaemic stimulus of gastric acid secretion (Simici, Popescu, and Diculesco, 1927). These assumptions are that the acid response is an 'all-or-none' phenomenon which is (1) initiated when the blood sugar falls to a threshold value of 40-50 mg/100 ml; (2) not related to the degree of hypoglycaemia below this threshold; (3) not dependent on the fall in blood sugar; and (4) not related to the rate of fall of blood sugar.

Acid and Pepsin Dose-Response Studies to Insulin Hypoglycaemia in a Healthy Man

“…The secretion of acid in response to insulin presented here agrees with those of previous dose-response studies in healthy man [2,4], These workers found the secretion of acid in response to insulin was related to both the dose of insulin and the degree of hypoglycaemia. This relationship has since been reported in man when the insulin was given by continuous intravenous in fusion [3], In the two healthy men previously reported very low levels of blood glucose, which did not necessarily occur after the largest dose of insulin, were associated with an inhibition of acid secretion.…”

“…The variables of gastric acid and blood glucose were expressed as described by Baron [2]. Variables of peptic activity were expressed as follows: basal pepsin output (BPO) was the sum of the peptic activity in the four samples expressed as U x I03/Ii.…”

“…Such relationships can best be studied by testing the responses to dilferent doses of insulin in a single person rather than a group of subjects [2] and we have examined these in a healthy man.…”

“…Inhibition of secretion was not observed with the lowest levels of hypoglycaemia attained. In health, insulin hypoglycaemia provides a quantitative glycopenic stimulus which produces a quantitative and parallel response for both acid and pepsin.The gastric acid response to insulin is not an all or none phenomenon but is dependent on the dose of insulin and level of hypoglycaemia attained [1,2,4], Studies in man have suggested that the gastric secretion of pepsin in response to insulin may parallel the secretion of acid [8] but the relationship between dose of insulin, degree of hypoglycaemia and the secretion of acid and pepsin has not been studied. Such relationships can best be studied by testing the responses to dilferent doses of insulin in a single person rather than a group of subjects [2] and we have examined these in a healthy man.…”

The effect of vagotomy on the lower oesophageal sphincter: A manometric study

“…These include the insulin test (Hollander, 1948), the ratio of peak acid outputs after insulin and pentagastrin (Baron, 1969) and the ratio of the insulin to histamine acid output (Hunt, 1950). Each has certain drawbacks and occasionally fails owing to difficulties in interpretation and the problem of sample collection in the presence of a drainage procedure.…”