Circadian rhythm of exocrine pancreatic secretion in rats: major and minor cycles

Maouyo, Djikolngar; Sarfati, Patrice D.; Guan, Difu; Morisset, J.; Adelson, Joel W.

doi:10.1152/ajpgi.1993.264.4.g792

Cited by 26 publications

(24 citation statements)

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“…This confirms the observations of cyclic nonparallel exocytotic secretion, as determined by enzyme assays in the rabbit (8) and the conscious rat (24,25). The degree of correlation between enzymes during secretion was dependent upon both the enzyme species and the stimulus.…”

Section: Discussionsupporting

confidence: 88%

Pancreatic digestive enzyme secretion in the rabbit: rapid cyclic variations in enzyme composition.

Adelson

Clarizio

Coutu

1995

Proc. Natl. Acad. Sci. U.S.A.

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The role and mechanism of nonparallel pancreatic secretion of digestive enzymes, in which enzyme proportions change in rapidly regulated fashion, remain controversial. Secretion was collected from male 2.2-kg New Zealand rabbits in 5-min The pancreas is a major organ of digestion, producing gram quantities of digestive enzymes daily in the human. The enzyme mixture is composed of -24 species that hydrolyze a diverse mixture of polymeric substrates. The basic question of whether the relative proportions of the specific enzyme species in the mixture can be rapidly adjusted to reflect the immediate requirements for intraluminal intestinal hydrolysis dates back to the work of Pavlov who demonstrated "nonparallel" changes in the enzyme mixture after administration of different digestive substrates. Nearly a century later, the subject is still disputed (1).Recently, the debate has been reformulated in terms of cell biological secretory mechanisms, especially the vectorial secretion of cellular products by exocytosis. On the one hand, a substantial number of observations have been made, usually in the intact pancreas, of rapid nonparallel secretion of enzymes after administration of digestive substrates, end products, gastrointestinal hormones, and hormone-like factors (2). These observations have led to a dispute concerning the basic concept that the prepackaged digestive enzymes are secreted en masse by exocytosis of the mixed contents of the secretory (zymogen) granules, since this would necessarily result in parallel secretion.Others (3-7), citing the requirement of the exocytosis mechanism for parallel discharge of granule contents, have disputed the very existence of nonparallel secretion, claiming it to be due to experimental artifact. Both schools have assumed that the exocrine pancreas is a homogeneous organ in which the mixed enzymes are distributed in secretion granules throughout the gland. Recently, a way has been found that may resolve the apparent paradox: this laboratory has shown (8, 9) that digestive enzymes can be secreted in a regulated but nonparallel fashion consistent with exocytosis from heterogeneous sources in the pancreas, and differential secretion from these sources would accommodate both exocytosis and nonparallel secretion. Others (10) have shown that individual zymogen granules may contain differing proportions of enzymes. We show here that nonparallel secretion is a primary characteristic of pancreatic function and, surprisingly, that under constant conditions, digestive enzymes are secreted in a cyclic neurosecretory-like fashion. MATERIALS AND METHODSCollection of Pancreatic Juice. Male albino New Zealand rabbits (2.2 kg), fed chow (Purina), were fasted overnight but allowed water before cannulation of the pancreas as described (9). The rabbits were anesthetized by i.p. administration of xylazine (12.5 mg/kg) and inhaled methoxyflurane and 02-Ringer's lactate solution and secretagogues dissolved in Ringer's lactate were infused at 15 ml/h via the femoral vein. A 1-h constant...

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Section: Discussionsupporting

confidence: 88%

Pancreatic digestive enzyme secretion in the rabbit: rapid cyclic variations in enzyme composition.

Adelson

Clarizio

Coutu

1995

Proc. Natl. Acad. Sci. U.S.A.

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“…Examples of circadian rhythms in the secretion of proteins comprise many liver-produced proteins, including fibrinogen and coagulation factors [ 121, proteins secreted by the exocrine pancreas [13], and the biliary output of lysosomal enzymes [19]. Unless, when newly synthesized, these proteins are protected by entering the secretory pathway, they are rapidly degraded [20-231.…”

Section: Discussionmentioning

confidence: 99%

“…We considered that a move of this kind, from a lower to a higher level of plateau enrichment, might be indicative of a pool of protein which turned over with life-time kinetics, with label sequestered in the protein being returned to the precursor pool after a defined period [S]. Circadian rhythms in protein degradation might also account for the change, and have been described for proteins produced in the liver [12], exocrine pancreas [13] or the remodelling of bone [14]. In a theoretical exploration of the mathematics of a model of this kind, we were able to demonstrate that if such a pool were to exist, there would be no effect upon the ultimate level of plateau enrichment, but the curve to plateau would show a succession of steps In the present study we have sought direct experimental evidence for a 'step' in the enrichment in urinary ammonia, and hence evidence for a pool of proteins which turn over with life-time kinetics.…”

Section: Introductionmentioning

confidence: 99%

Enrichment in Urinary Ammonia and Urea with Hourly Oral Doses of [15N]glycine: Evidence for a Step Function and a Circadian Rhythm in Protein Turnover

et al. 1997

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1. The present study sought to determine the possible existence of a pool of proteins which turn over with life-time kinetics. The pattern of enrichment of ammonia and urea in hourly samples of urine was determined in normal adults to whom oral doses of [15N]glycine were given hourly for 36 h. The subjects received hourly meals throughout, and in six the study commenced at 06.00 hours, in five at 12.00 hours and in two at 18.00 h. 2. A plateau level of enrichment was achieved in urinary ammonia within 4-6 h. Regardless of the time at which the study started this plateau was held until about midnight, at which time there was an increase in enrichment, with a second higher plateau 5-6 h later. The second plateau was held to the end of the study. For urinary urea the rate of rise in enrichment was slower and smoother, because of the slow turnover of the urea pool. 3. Protein synthesis, derived from the first ammonia plateau, 179 mg h-1 kg-1, was significantly higher than that derived from the second plateau, 118 mg h-1 kg-1. Using the plateau in urea towards the end of the 36 h, the estimate of protein synthesis was 153 mg h-1 kg-1. 4. The results are considered to provide evidence of a pool of proteins for which degradation takes place in harmony with a circadian rhythm.

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“…Experiments were carried out between 9 and 11 AM to avoid possible circadian variations of the pancreatic exocrine secretion (25). Overnight fasted animals were anesthetized with urethane (1.2 g/kg ip), and the left jugular vein was cannulated for the infusion of saline (control group) or ANF and/or other secretagogues.…”

Section: Pancreatic Secretion Experimentsmentioning

confidence: 99%

Atrial natriuretic factor negatively modulates secretin intracellular signaling in the exocrine pancreas

Sabbatini¹,

Vatta²,

Davio³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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Circadian rhythm of exocrine pancreatic secretion in rats: major and minor cycles

Cited by 26 publications

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Pancreatic digestive enzyme secretion in the rabbit: rapid cyclic variations in enzyme composition.

Pancreatic digestive enzyme secretion in the rabbit: rapid cyclic variations in enzyme composition.

Enrichment in Urinary Ammonia and Urea with Hourly Oral Doses of [15N]glycine: Evidence for a Step Function and a Circadian Rhythm in Protein Turnover

Atrial natriuretic factor negatively modulates secretin intracellular signaling in the exocrine pancreas

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