Relation of Gastric Secretory Response in Man to Dose of Insulin

Isenberg, Jon I.; Stening, G. Frank; Ward, S; Grossman, Morton I.

doi:10.1016/s0016-5085(19)33870-3

Cited by 45 publications

(7 citation statements)

References 8 publications

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“…In repeated tests in one human subject he refuted the 'all-or-none' hypothesis, finding that peak 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. Similar graded responses to increasing doses of insulin in man have been reported by lsenberg, Stening, Ward, and Grossman (1969), in the dog by Cooke (1969), and in the cat by Stening and Isenberg (1969).…”

Section: Discussionsupporting

confidence: 83%

The gastric secretory response to insulin: an `all-or-none' phenomenon?

Spencer¹,

Grossman²

1971

Gut

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SUMMARY Dogs were prepared with Pavlov pouches which could be perfused with saline so as to detect rapidly changes occurring in acid secretion.Dose-response studies were performed by the intravenous injection of insulin (0-06, 0-12, 0.25, 0-5, or 1-0 unit/kg). Both the magnitude of peak response and the duration of response were dose-related and both were related to the magnitude of fall in plasma glucose.These results are not consistent with an 'all-or-none' hypothesis for insulin-stimulated gastric acid secretion, but favour the alternative hypothesis that insulin provides a graded glycopenic stimulus producing a graded secretory response.It has long been held that the gastric secretory response to insulin hypoglycaemia is an 'all-or-none' phenomenon, initiated when the blood sugar falls below a certain threshold value (40-50 mg/100 ml) and giving a peak response whose magnitude is unrelated to the degree of hypoglycaemia. These assumptions have recently been questioned by Baron (1970), who suggested that insulin hypoglycaemia provided a graded glycopenic stimulus producing a graded vagal response. On repeated studies in one human subject Baron found that peak acid output after insulin was significantly correlated with the lowest blood glucose achieved after insulin, or with the fall-or rate of fall of blood glucose. In these studies peak acid output was defined as that in the two consecutive 15-minute samples giving the highest acid output. It is possible, however, that peak acid output in a much shorter period may be the same with all doses of insulin, but that the duration of the secretory response may be greater when hypoglycaemia is prolonged. The 'all-or-none' assumption would in this case be valid, but would appear refuted when long collection periods were used to define acid output. It was to test this hypothesis that the present experiment was carried out. Dogs were prepared with innervated (Pavlov) pouches which were perfused with saline so that changes in acid secretion could be detected rapidly. Dose response studies were then performed to determine the secretory response to insulin. MethodsTwo mongrel dogs (20.4 and 26-3 kg) were each prepared with a gastric fistula and an innervated fundic pouch (Pavlov). Two Gregory cannulae drained the pouch, at its upper and lower ends (Fig. 1). After a three-week recovery period secretory studies were begun in each dog. These were performed after an overnight fast, during which water but not food was available. The animals stood on tables supported by cloth slings. During each test 154 mM NaCl was infused into a leg vein at a rate just sufficient to maintain patency in a polyethylene cannula which was used to obtain blood samples. In an initial test histamine dihydro-chloride was infused intravenously at a dose of 0-16 mg/kg/hr in order to provide an index of 'maximal' pouch secretion. Pouch secretions were collected as 15-minute samples for two hours. Gastric fistula secretion in this and subsequent studies was collected and discarded.In subsequent studies ...

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Section: Discussionsupporting

confidence: 83%

The gastric secretory response to insulin: an `all-or-none' phenomenon?

Spencer¹,

Grossman²

1971

Gut

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“…However, the present results suggest that an insulin dose of about 0.2 u/kg may be optimum in producing sufficient hypoglycaemia (blood glucose below 30 mg/100 ml) to guarantee initiation of gastric secretion in an individual, to ensure a near maximum vagal acid output, and to prevent blood glucose falling so low (below 15 mg/100 ml) that hypoglycaemic inhibition of gastric secretions or dangerous side effects are produced. Addendum Isenberg, Stening, Ward, and Grossman (1969) gave intravenous injections of insulin (0.025-0.4 u/kg) to five healthy men. Peak 15-minute acid output was similar after 0-1, 0.2 and 0.4 u/kg and highest after 0.2 u/kg.…”

Section: In the Unoperated Subjectmentioning

confidence: 99%

Dose response relationships of insulin hypoglycaemia and gastric acid in man

Baron¹

1970

Gut

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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.

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“…The doses tested were similar to those of Isenberg et al (1969) -that is, 0-025, 0 05, 0-1, 0-2, and 0 4 U/kg body weight. The insulin was rapidly administered by the intravenous route.…”

mentioning

confidence: 70%

“…Several studies published in recent years have now established that 0-2 U insulin/kg body weight provides an effective dose for stimulation of gastric acid secretion in subjects of the Western countries (Isenberg et al, 1969;Baron, 1970;Isenberg et al, 1970;Baron and Cowley, 1971;Baron et al, 1972;Cowley and Baron, 1973). However, in Indian subjects an effective dose of insulin to stimulate gastric secretion has not been established, although various studies of histamine stimulated gastric acid secretion have been reported (Vakil and Mulekar, 1965;Goyal et al, 1966;Desai et al, 1967;Desai et al, 1969).…”

mentioning

confidence: 99%

Histamine and insulin dose-response studies of gastric secretion in Indian control subjects and patients with duodenal ulcer in the Ganges delta

Jalan¹,

Mahalanabis²,

Maitra³

et al. 1978

Gut

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SUMMARY The gastric secretory responses to various doses of histamine and insulin have been studied in 11 control and 12 duodenal ulcer subjects belonging to the Ganges delta of India where the incidence of duodenal ulcer disease is known to be high. A dose of 0*04 mg/kg body weight of histamine acid phosphate was sufficient to produce peak gastric acid output both in the control and duodenal ulcer subjects. However, a dose as low as 0-025 U insulin/kg body weight was enough to produce peak rates of gastric acid output in duodenal ulcer subjects, whereas in the controls a minimum dose of 0 05 U insulin/kg body weight was sufficient. A greater proportion of the duodenal ulcer patients also showed a peak acid secretory response in the first hour after administration of insulin. Furthermore, increasing doses of insulin in this population did not produce lower levels of blood glucose but did produce increasingly high acid output as subjects do in the West. K values derived from the intravenous glucose tolerance test showed that 75% of duodenal ulcer patients and 54% of the controls had variable degrees of intolerance to glucose. Gastric acid secretion in response to a bolus of 50 ml 50% intravenous glucose was also studied in a separate group of 16 duodenal ulcer and 13 control subjects. A sharp rise in the volume, titratable acidity, and total acid output was observed in the early part of the fourth hour in the control and duodenal ulcer subjects. In a separate group of controls a bolus of intravenous hypertonic saline produced no such increase in gastric acid secretion.

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Relation of Gastric Secretory Response in Man to Dose of Insulin

Cited by 45 publications

References 8 publications

The gastric secretory response to insulin: an `all-or-none' phenomenon?

The gastric secretory response to insulin: an `all-or-none' phenomenon?

Dose response relationships of insulin hypoglycaemia and gastric acid in man

Histamine and insulin dose-response studies of gastric secretion in Indian control subjects and patients with duodenal ulcer in the Ganges delta

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