Effects of Secretin on Insulin and Glucagon in Portal and Peripheral Blood in Man

Dupré, J.; Rojas, Leonor; White, J. J.; Unger, Roger H; Beck, J. C.

doi:10.1016/s0140-6736(66)91750-8

Cited by 109 publications

(20 citation statements)

References 14 publications

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“…Pfeiffer and associates (12) and McIntyre, Turner, and Holdsworth (13) noted in 1965 that the incubation of secretin with pieces of dog and rabbit pancreas enhanced the release of insulin. More recently, preliminary in vivo evidence of an insulinreleasing effect of secretin has been reported in dogs (14) and in humans (15). The present study was designed to explore in dogs the effects of the enteric hormones secretin and pancreozymin-cholecystokinin and the antral hormone gastrin on insulin and glucagon secretion.…”

Section: Introductionmentioning

confidence: 99%

The Effects of Secretin, Pancreozymin, and Gastrin on Insulin and Glucagon Secretion in Anesthetized Dogs *

Unger¹,

Ketterer²,

Dupré³

et al. 1967

J. Clin. Invest.

341

110

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Summary. The effects upon islet hormone secretion of highly purified preparations of secretin and of pancreozymin-cholecystokinin and of a crude gastrin-containing extract of hog antrum have been studied in acutely operated dogs. All three preparations were shown to cause a striking increase in insulin concentration in the pancreaticoduodenal venous plasma after their rapid endoportal injection in anesthetized dogs. With each hormone preparation, the peak in insulin secretion occurred 1 minute after injection, and a rapid decline was observed immediately thereafter. Whereas secretin and gastrin failed to alter significantly the pancreaticoduodenal venous glucagon or arterial glucose concentration, pancreozymin caused a dramatic rise in pancreaticoduodenal venous glucagon concentration, which reached a peak 3 minutes after injection, and hyperglycemia was noted to occur soon thereafter. Endoportal infusion of secretin and pancreozymin for 20 minutes caused responses that were sustained but qualitatively identical to the responses noted after rapid injection of the hormones. The beta-cytotropic effect of secretin was abolished by the infusion of epinephrine.These results could not be attributed to the small degree of contamination of the enteric hormone preparations with insulin or glucagon, and it would appear that secretin, pancreozymin, and probably gastrin have insulin-releasing activity and that pancreozymin has, in addition, glucagon-releasing activity.The demonstration that these three hormones possess insulin-releasing activity suggests that there is in the gastrointestinal tract a chain of betacytotropic hormones from antrum to ileum that is capable of augmenting insulin secretion as required for disposal of substrate loads. It is suggested that the existence of this "entero-insular axis" prevents high substrate concentrations that would otherwise follow ingestion of large meals were the insular response entirely a function of arterial substrate concentration. Introductionbe influenced by humoral factors of the gastro-

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Section: Introductionmentioning

confidence: 99%

The Effects of Secretin, Pancreozymin, and Gastrin on Insulin and Glucagon Secretion in Anesthetized Dogs *

Unger¹,

Ketterer²,

Dupré³

et al. 1967

J. Clin. Invest.

341

110

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“…A duodenal factor with the ability to alleviate diabetes mellitus was postulated in 1906 (1), but the importance Dr. Chisholm's present address is Frazer Laboratory, Department of Endocrinology, Royal Victoria Hospital, Montreal, Canada. Received for publication 27 January 1969 and in revised form 8 April 1969. of gastrointestinal hormones in the release of insulin has only recently gained acceptance. Dupre (2) demonstrated increased utilization of intravenous glucose when preceded by an oral glucose load or accompanied by intravenous secretin; alimentary administration of glucose produced a greater and earlier release of insulin than did glucose given intravenously (3)(4)(5)(6); and a similar augmentation of insulin release was seen when intraduodenal administration of an amino acid was compared with an intravenous infusion producing comparable blood amino nitrogen levels (7).…”

Section: Introductionmentioning

confidence: 99%

“…Secretin, administered intravenously in pure or crude form, has induced insulin release in dogs and humans (2,(8)(9)(10)(11)(12), and studies with in vitro preparations have also confirmed the ability of secretin to release insulin from the pancreas (13,14). Other gastrointestinal hormones including gastrin, pancreozymin-cholecystokinin, and glucagon when given parenterally have resulted in the elevation of serum insulin levels (15,16,10,11) and, in addition, evidence has been presented for a vagal influence on insulin release (17,18).…”

Section: Introductionmentioning

confidence: 99%

The gastrointestinal stimulus to insulin release

Chisholm¹,

Jd²,

Lazarus³

1969

J. Clin. Invest.

121

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A B S T R A C T The gastrointestinal stimulus to the release of insulin has been investigated in man by the use of a radioimmunoassay for secretin. Serum secretin levels rose rapidly after the oral ingestion of glucose or protein and preceded the elevation of serum insulin. An intravenous infusion of highly purified secretin caused a release of insulin when the serum secretin levels were within the physiological range.Infusion of hydrochloric acid into the duodenum caused an elevation of serum secretin and serum insulin levels in normal subjects. A similar response of secretin and insulin was seen after intravenous infusion of pentagastrin even when the acid stimulus to the duodenum was prevented. The latter observation suggests that pentagastrin (and probably gastrin) releases secretin by a direct humoral effect which is later fortified by the arrival of gastric acid in the duodenum.These studies suggest that secretin participates in the augmentation of insulin release after oral stimuli, and that a rapid sequence of humoral events takes place, gastrin releasing secretin and secretin releasing insulin. Subsequently secretin release would be augmented by a local stimulus in the duodenum and insulin release by the rising level of blood glucose or amino acids.This humoral system, which could also involve other gastrointestinal hormones, would provide a mechanism for facilitating the release of insulin to coincide with the onset of metabolite absorption.

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“…As a precautionary measure, pyloric ligation was undertaken to prevent the passage of chyme into the duodenum to avoid the release of gastro-intestinal hormones viz. gastrin, cholecystokinin, secretin and gastric inhibitory polypeptide, which have an insulinotropic action [87,88,89]. Bilateral vagotomy was also undertaken since the vagus nerves stimulate insulin release [90].…”

Section: Discussionmentioning

confidence: 99%

Investigations into the absorption of insulin and insulin derivatives from the small intestine of the anaesthetised rat

McGinn¹,

Morrison

2016

Journal of Controlled Release

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Investigations into the absorption of insulin and insulin derivatives from the small intestine of the anaesthetised rat. Journal of Controlled Release, 232, pp. 120-130. (doi:10.1016Release, 232, pp. 120-130. (doi:10. /j.jconrel.2016 This is the author's final accepted version.There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it.http://eprints.gla.ac.uk/120651/ ABSTRACTExperiments have been undertaken to determine the extent to which cholic acid conjugates of insulin were absorbed from the small intestine of anaesthetised rats by means of the bile salt transporters of the ileum. The measure used to assess the absorption of the cholyl-insulins was the amount of hypoglycaemia following infusion into the small intestine. Control experiments involving infusion of natural insulin into the ileum showed either nil absorption or absorption of a small amount of insulin as indicated by transient dip in the blood glucose concentration. However, when insulin was co-infused with the bile salt taurocholate, this was followed by a marked hypoglycaemic response which was specific to the ileum and did not occur on infusion into the jejunum. When the two cholyl conjugates of insulin were tested viz. B 29 -Lys-cholyl-insulin and B 1 -Phe-cholyl-insulin, both were biologically active as indicated by hypoglycaemic responses on systemic injection, though their potency was about 40% of that of natural insulin. While there was no evidence for the absorption of B 29 -Lys-cholyl-insulin when infused into the ileum, B 1 -Phe-cholyl-insulin did cause a long lasting hypoglycaemic response, indicating that absorption had occurred. Since the hypoglycaemic response was blocked on co-infusion with taurocholate and was absent for infusion of the conjugate into the jejunum, these results were taken as evidence that B 1 -Phe-cholyl-insulin had been taken up by the ileal bile salt transporters. This would indicate that B 1 -Phe-cholyl-insulin is worthy of further investigation for use in an oral insulin formulation.

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Effects of Secretin on Insulin and Glucagon in Portal and Peripheral Blood in Man

Cited by 109 publications

References 14 publications

The Effects of Secretin, Pancreozymin, and Gastrin on Insulin and Glucagon Secretion in Anesthetized Dogs *

The Effects of Secretin, Pancreozymin, and Gastrin on Insulin and Glucagon Secretion in Anesthetized Dogs *

The gastrointestinal stimulus to insulin release

Investigations into the absorption of insulin and insulin derivatives from the small intestine of the anaesthetised rat

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