The traditional understanding is that an entirely new complement of digestive enzymes is secreted by the pancreas into the small intestines with each meal. This is thought to be necessary because, like food itself, these enzymes are degraded during digestion. In this review we discuss experiments that bring this point of view into question. They suggest that digestive enzymes can be absorbed into blood, reaccumulated by the pancreas, and reutilized, instead of being reduced to their constituent amino acids in the intestines. This is called an enteropancreatic circulation of digestive enzymes.

The exocrine pancreas and certain salivary glands of mammals secrete a variety of enzymes into the gastrointestinal tract, where they digest food. The same glands also release these enzymes into the bloodstream. This latter process has commonly been assumed to occur solely as the result of a pathological condition or as an inadvertent by-product of exocrine secretion due to the leakage of trace quantities of the enzymes into blood. However, a variety of evidence suggests that the endocrine secretion of digestive enzymes is a normal occurrence that can be of substantial magnitude in healthy individuals, is responsive to various physiological stimuli, and is distinct from exocrine secretion. Recent research has focused attention on this process as a promising means for the delivery of engineered proteins into the systemic circulation for pharmaceutical purposes. In this review, we survey research in this area and consider the evidence for the existence of an endocrine secretion of digestive enzymes, the cause of enzyme release into the bloodstream, its source within the tissue, and, finally, the physiological purposes that this secretion process might serve.

No abstract

No abstract

The importance of unconscious intelligence and intuition is increasingly acknowledged by the scientific community. This essay examines and assesses the varied views on the topic presented in three books that bridge the scientific world and reading public: Blink by Malcolm Gladwell (2005), Gut Feelings by Gerd Gigerenzer (2008), and How Doctors Think by Jerome Groopman (2007). The analysis differentiates among kinds of unconscious intelligence and points towards a more complete understanding of the higher cognitive potential of the unconscious mind.

When fluid secretion by the pancreas was mechanically blocked, amylase secretion into the duct ceased. When flow was reduced in a graded fashion by the application of a back pressure, amylase output was reduced proportionately and amylase concentration in secretion was maintained constant. Thus, the secretion of digestive enzyme from the cell into the duct appears to be dependent upon the concentration of enzyme in the duct system. This behavior is most simply explained by diffusion-like (concentration dependent, bidirectional) fluxes of digestive enzyme across the plasma membrane. A unidirectional process, such as exocytosis, whose rate should be unaffected by fluid flow, cannot readily explain these results.

The flux of a-amylase (1,4-a-D-glucan glucanohydrolase; EC 3.2.1.1) across the basolateral membrane of the acinar cell was measured in the cell-to-bath direction using the whole rabbit pancreas in organ culture. This in vitro preparation is polarized so that apical and basolateral secretions can be collected separately. The unstimulated amylase flux from cell to bathwas substantial at the initial rate (approximately three times the concurrent apical flux). With time, bath amylase au proached a steady-state concentration, suggesting an equsiibrating process. During the same time interval, ductal amylase secretion remained constant. At the steady state, the amylase concentration in the bath was at least an order of magnitude less than its ductal concentration. HQurly replacement of bathing medium reproduced the initial rate of amylase release into the bath for five consecutive hours. Pancreozymin (cholecystokinin), a peptide hormone, did not alter the steady-state bath amylase content, although it greatly augmented ductal amylase secretion. In contrast, a cholinergc agonist greatly increased both the flux from the cell to bath and the ductal secretion of amylase. Taken together, these results indicate a natural bidirectional permeability of the basolateral membrane to digestive enzyme and support evidence previously obtained suggesting that such a permeability might exist. The interior of the pancreatic acinar cell is highly polarized; the rough-surfaced endoplasmic reticulum is located predominantly at the basal or blood-facing side of the cell, while the digestive enzyme-containing secretion granules, the zymogen granules, are concentrated at the cell's apex or its duct-facing surface. A functional analog of this anatomical polarization for the secretion of digestive enzymes is assumed in the popular hypothesis that new protein is synthesized at the basal portion of the cell and moved through a series of membrane-bound compartments to the apical surface, where it is secreted into the duct system by the exocytosis of zymogen granule contents. This construct has been called "vectorial transport" because it proposes that the movement of the secretory product is constrained to one direction, i.e., from the basal part of the cell to the duct lumen. In this formulation, only the apical membrane of the acinar cell allows the passage of digestive enzyme, and only in the cell-to-duct direction (1).Studies that have examined the kinetics of the secretory process directly are in conflict with this "vectorial transport" concept in a number of areas. Not only is the apical membrane apparently permeable in both the cell-to-duct and duct-to-cell direction (2), but similar bidirectional fluxes have been described for digestive enzyme across the zymogen granule membrane (3). Indeed, in this paper we present evidence that the basolateral (blood-facing) membrane of the cell also is bidirectionally permeable to these large molecules. In addition, the evidence suggests that these fluxes are all related by a cy-The costs of ...

No abstract