Pancreatic Lobules Research Articles

Effect of glucagon on the secretory process in the rat exocrine pancreas.

Glucagon was infused into conscious rats in doses of 10 to 80 microgram/h for periods up to 24 h. The effect on the secretory process of the exocrine pancreas was studied in vitro using isolated pancreatic lobules. A pronounced inhibition of the rate of protein synthesis and discharge of stored and newly synthesized proteins combined with increased enzyme content in the pancreas were observed after 30 min infusion. This effect was absent after longer infusion periods of up to six hours. After 12 to 24 h infusions a marked degranulation and decrease in enzyme content was observed. While the rate of protein synthesis was not significantly enhanced, both the basal and stimulated discharge of enzymes from the pancreas were increased. The results suggest a biphasic response of the pancreas to prolonged glucagon infusion.

Hormone-Induced Cyclic Guanosine Monophosphate Secretion from Guinea Pig Pancreatic Lobules

Carbamylcholine (30 micronM) increased the concentration of guanosine 3',5'-monophosphate (cyclic GMP) in guinea pig pancreatic lobules about eight-to tenfold over the basal concentration in 30 seconds with a concomitant increase in the rate of amylase secretion. The concentration of cyclic GMP rapidly declined to a plateau value of about 16 percent of the peak level in 10 minutes. Cellular cyclic GMP decreased, mostly because the nucleotide was secreted into medium; cellular adenosine 3',5'-monophosphate (cyclic AMP), however did not change, nor was this nucleotide secreted into the medium. An immunocytochemical technique showed that cyclic GMP was distributed in the apical plasmalemma membrane and lumen of the pancreas. Carbamylcholine increased the cyclic GMP fluorescence in tha apical plasmalemma membrane within 30 seconds, and in zymogen granules and the plasma membrane in the apical part of acinar cells in 10 minutes. The islets of Langerhans did not show any change in cyclic GMP. Fluorescence of cyclic AMP in pancreatic lobules was not altered by carbamylcholine and was localized along the apical portion of plasmalemma and cytoplasm. Cyclic GMP may thus participate either in the process of exocytosis or in the activation of enzymes secreted from the pancreas.

Rat pancreas adenylate cyclase V its presence in isolated rat pancreatic acinar cells

1. (1) In order to determine the cellular localization of the secretin- and pancreozymin-sensitive adenylate cyclase in rat pancreas, the occurence of this enzyme system has been investigated in isolated pancreatic cells. 2. (2) Digestion of rat pancreatic lobules with collagenase yields a preparation of isolated cells which upon differential morphological analysis appears to consist for 97% of acinar cells and to contain far fewer centro-acinar and ductal cells than undissociated lobules. 3. (3) Expressed per mg protein, the isolated cells contain the same amount of DNA, chymotrypsin and lactic dehydrogenase as the undissociated tissue. The stimulated adenylate cyclase activity is nearly entirely recovered in the isolated acinar cells, as is also the case for the low K m adenosine 3′,5′-cyclic monophosphate phosphodiesterase activity and the adenosine 3′,5′-cyclic monophosphate (cyclic AMP) content. Marked losses are noted for the basal adenylate cyclase and the high K m cyclic AMP phosphodiesterase activities. 4. (4) Washing the isolated acinar cells in Krebs-Ringer bicarbonate medium containing 10 mM 1-methyl-3-isobutylxanthine causes a cyclic AMP level 2.6 times that in cells washed in Krebs-Ringer bicarbonate alone. The cyclic AMP level is further increased by subsequently incubating the cells for 10 min in the presence of 3 · 10 −7 M pancreozymin-C-octapeptide or secretin to values 1.7 or 4.7 times the control level in cells incubated for 10 min with 1-methyl-3-isobutylxanthine alone. 5. (5) It is suggested that the adenylate cyclase of the acinar cells may be involved, with another factor, in the stimulation of enzyme secretion, whereas a ductular cyclase would function in the regulation of the bicarbonate-dependent fluid secretion.

Acute interstitial pancreatitis in the rat induced by excessive doses of a pancreatic secretagogue.

Conscious rats were infused via a jugular vein catheter with 5 x 10-6 g/kg/h caerulein for periods up to 24 h. On macroscopic inspection a progressive interstitial oedema is seen to develop in the pancreas, from one hour of infusion on and is most marked at twelve hours. This oedema is largely reabsorbed after 24 h treatment, but the pancreas is considerably indurated by this time. Serum amylase levels increase consistently to reach a tenfold elevation above controls after three, six or twelve hours infusion. Premature fusion of condensing vacuoles and secretory granules leads to formation of large vacuoles in the cytoplasm of exocrine pancreatic cells. These vacuoles fuse with the lateral and basal plasma membrane and realease their content into the extracellular space. Regular discharge of zymogen granules at the cell apex into the duct system does not occur. Vacuole formation is associated with cytoplasmic destruction of the pancreatic cells. The rate of protein synthesis decreases consistently as a result of these structural alterations and this change corresponds largely to a reduction of cellular respiration. Release of amylase from isolated pancreatic lobules of caerulein infused animals shows a progressive increase of unstimulated discharge, while in vitro stimulation with 5 x 10-6M carbamylcholine gives secretion patterns of wash-out kinetics. Stimulated discharge of labeled secretory proteins indicates a progressive reduction in the in vitro sensitivity of the pancreatic cells to secretagogues. After 24 h infusion of 5 x 10-6 g/kg/h caerulein the pancreatic lobules are totally insensitive to the in vitro effect of carbamylcholine or caerulein.

Studies on secretory glycoproteins in the rat exocrine pancreas. I. Fine structure of the Golgi complex and release of fucose-labeled proteins after in vivo stimulation with caerulein.

Using a double-label technique on isolated rat pancreatic lobules, the rate of synthesis and discharge of regular and fucosylated secretory proteins was studied under control conditions and after in vivo prestimulation with caerulein. Both labeled leucine and fucose were incorporated into pancreatic proteins at a linear rate, which was potentiated by in vivo stimulation. In pulse-chase experiments both regular and fucosylated secretory proteins were discharged into the medium in parallel. The in vivo pretreatment with caerulein caused an earlier discharge and increased the total amount released. Kinetic analysis of unstimulated (baseline) discharge of both classes of secretory proteins indicated in vitro sensitivity by the previous in vivo treatment with caerulein. The biochemical data were compared to the fine structure of the Golgi complex under both control and prestimulated ocnditions. The Golgi stacks were composed of four to six individual cisternae which in some cases were connected by intercisternal pores. Transporting vesicles were observed fusing along the total length of the outermost cisterna on both the cis- and trans-side and with the lateral ends of the intermediate cisternae. Under control conditions only the last trans-cisterna contained some electron opaque material; in vivo prestimulation led to distension and filling of all disternae in an individual Golgi-unit. Numerous stages of transformation of the last transcisterna into condensing vacuoles were observed, lending support to the hypothesis that during packaging of secretory products the membranes of the Golgi complex undergo a continuous turnover.

Exocrine pancreas under experimental conditions

The in vitro formation of paracrystalline structures after addition of high concentrations of amino acids to the incubation medium was investigated in pancreatic lobules and pancreatic homogenates. It could be shown that even in the homogenate, pCPA induced the formation of paracrystalline structures which exhibited the same ultrastructural arrangement as seen in the in vivo induced paracrystalline inclusions in the RER of the rat pancreas. In correlation with the morphological alterations, the functional consequences to the secretory process, i.e. amylase discharge,discharge of pulse-labeled proteins and incorporation of 3H-leucine into pancreatic proteins,were studied in pancreaticlobules. Two different approaches were used. Firstly, the effect of pCPA-pretreatment of rats and secondly, the effect of higher pCPA concentrations in the incubation medium on the secretory process in untreated pancreatic lobules were studied. A nonparallelism of inhibition of the three different steps of the secretory process depending, with respect to its extent,on time after pCPA-application (4-72 h) and on the concentration of pCPA (1-10(-5) to 1-10(-2) M) in the incubation medium was found. In addition to specific effects probably due to pCPA and to the paracrystalline inclusions, unspecific alterations, particularly accompanying degenerative processes after in vivo pretreatment, could be differentiated.

Extracellular calcium and the organization of tight junctions in pancreatic acinar cells

In pancreatic lobules incubated in Ca 2+-free Krebs-Ringer bicarbonate solution +0.5 mM EGTA tight junctions are first disarrayed and then break up into fasciae occludentes and small fibrillar fragments, which move laterally in the plane of the plasmalemma and often wind up around the gap junctions. The interruption of the continuity of tight junctions results in the disappearance of the difference in intramembranous particle density between the lateral and luminal regions of the plasmalemma. These results are consistent with the interpretation of tight junctions as dynamic structures, probably resulting from a specific polymerization of intramembranous particles and confirm that tight junctions might have a role in establishing and maintaining the regional differences of the plasmalemma.

Cellular cyclic nucleotides and enzyme secretion in the pancreatic acinar cell.

Cellular levels of cAMP and cGMP were measured in guinea pig pancreatic lobules incubated in vitro, during basal or stimulated secretion. Stimulation with optimal concentrations of carbamylcholine (carbachol) (10(-5) M), pancreozymin (0.1 unit/ml), and caerulein (10(-9) M) resulted within seconds in a sharp rise in cGMP levels, from five to more than 20 times that of basal levels. cAMP levels did not change significantly. cGMP increases were maximal at 2 min then subsided by 4-7 min to a plateau about two to three times that of basal level. This plateau was maintained for the duration of the secretagogue stimulus. Removal of the carbachol stimulus resulted in a rapid decrease in cGMP levels to that of the basal state. The cellular cGMP levels observed within the first 2 min of stimulation correlated closely with the dose of carbachol and the secretory response. Atropine at 10(-4) M blocked the cGMP elevation due to carbachol but not that due to pancreozymin, while carbonyl cyanide m-chlorophenyl hydrazone, an uncoupler of oxidative phosphorylation, blocked the response to both secretagogues. Similar though less extensive findings were observed using rabbit pancreatic lobules incubated in vitro. High concentrations (10(-2)-10(-3) M) of the dibutyryl and 8-bromo analogues of both nucleotides were effective, though suboptimal, secretagogues. In the case of the cAMP analogues, the secretory response was associated with a rise in endogenous cGMP levels, similar to that observed during suboptimal carbachol stimulation. These findings suggest that cGMP may be an intracellular mediator in the process of stimulus secretion coupling in the acinar cell of the exocrine pancreas.

Studies on intracellular transport in the rat exocrine pancreas. I. Inhibition by aromatic amino acids in vitro.

In vitro incubation of rat pancreatic lobules in the presence of 10 mM concentrations of 2 natural (phenylalanine, tryptophane) and 2 modified aromatic amino acids (p-fluorophenylalanine, p-chlorophenylalanine) induces paracrystal formation in the cisternal space of the rough endoplasmic reticulum and in the acinar lumen. Aggregation of secretory material in transitional elements of the rough endoplasmic reticulum suggests tubular connection to the Golgi complex. Paracrystal formation is correlated with a disturbance of the three major phases in the secretory process of the exocrine cell. Incorporation of radioactive amino acids into proteins is inhibited by 10 mM concentrations of phenylalanine and tryptophane by 20 and 50% respectively and by p-chlorophenylalanine at 1 and 10 mM concentrations by 50 and 75%. The inhibition of protein synthesis is not due to a reduced intracellular concentration of radioactive precursor amino acids. Intracellular transport of newly synthesized proteins as studied by a radioassay for zymogen discharge and by cell fractionation is similarly inhibited by phenylalanine, tryptophane and p-chlorophenylalanine at 10 mM concentrarions (20, 30, and 40% respectively). Discharge of zymogens as measured by the secretion of amylase stimulated with 5 X 10(-6) M carbamylcholine is reduced by 20% if 10 mM concentrations of phenylalanine, tryptophane or p-chlorophenylalanine are present in the medium. Paracrystals were isolated by differential centrifugation and their protein content compared with isolated zymogen granules. On sodium dodecylsulfate gel electrophoresis paracrystalline proteins show the same electrophoretic pattern as the content of zymogen granules.

Calcium and pancreatic secretion-dynamics of subcellur calcium pools in resting and stimulated acinar cells.

1 Pulse-chase experiments were carried out on pancreatic tissue lobules incubated in vitro, with 45Ca as the tracer, in order to shed some light on the functional significance of the calcium pools associated with the various cell organelles of the acinar cell, especially in relation to stimulus-secretion coupling. 2 The kinetics of tracer uptake and release which were observed in the intact lobules suggest the existence of a number of intracellular pools, whose rate of exchange is slower than that across teh plasmalemma. 3 The various subcellular fractions accumulate the tracer in different amounts: some (rough microsomes and postmicrosomal supernatant) showed little radioactivity and some (smooth microsomes and zymogen granule membranes) were heavily labelled; mitochondria and zymogen granules showed intermediate values. 4 The fractions are heterogeneous also in relation to the time course of uptake and release of the tracer: in rough and smooth microsomes and, especially, in the postmicrosomal supernatant both rates were fast; zymogen granules and zymogen granule membranes showed slow rates of uptake and little release during chase; intermediate rates were found in mitochondria. 5 In agreement with previous findings we observed that in 45Ca preloaded lobules, stimulation of secretion (brought about by the secretagogue polypeptide caerulein) results in an increase of the tracer release which seems to be due primarily to the rise of the intracellular concentration of free Ca2+ and to the consequent increase of the transmembrane Ca2+ efflux. Among the cell fractions isolated from stimulated lobules only the mitochondria exhibited a significantly lower 45Ca level relative to the unstimulated controls. 6 It is concluded that, of the organelle-bound calcium pools, that associated with the mitochondria might be involved in the regulation of the calcium-dependent functions, including stimulus-secretion coupling; the calcium associated with the zymogen granule content probably has a role in the architecture of the organelle and in the functionality of the pancreatic juice, while the calcium bound to the membrane of the granules might be concerned with the regulation of its permeability properties.

The effects of selective partial pancreatectomy on pancreatic islet cell morphology in the Japanese quail

The A- and B-islet containing splenic lobe of the Japanese quail pancreas was examined by light and electron microscopy after surgical removal of the ventral or third pancreatic lobe, and after a sham operation. Removal of the ventral lobe, which contains only B-islets, resulted in time-dependent alterations in the B-cell granules. Electron opaque material within the crystalline and ring-shaped secretory granules was less abundant in B-cells 2 hr after ventral lobectomy than after a sham operation. The uniformly opaque B-granules, however, were not altered until 6 hr after lobe removal. In contrast, extirpation of the A-islet containing third pancreatic lobe, but not the sham operation, resulted in granule alterations within the A-cells. Two and six hours after third-lobectomy decreases in electron opacity were observed at the peripheries of A-granules. These changes did not result in the formation of electron lucent halos around the majority of A-granule cores suggesting that a nonglucagon component exists within these granules. After removal of either the ventral or third pancreatic lobe increased amounts of rough endoplasmic reticulum, enlargement of Golgi profiles and increased granule numbers were noted in B- and A-cells, respectively, during the 12–48 hr interval following surgery. During this study no granule changes were observed in D- or Type IV cells. These results demonstrate that selective partial pancreatectomy may be used to produce specific cytological alterations in A- or B-cells of the endocrine pancreas of this species. Furthermore, these observations suggest that intracytoplasmic dissolution of secretory granules may play a role in the release of insulin and glucagon from B- and A-cells of the Japanese quail.

Studies on the guinea pig pancreas. Parallel discharge of exocrine enzyme activities.

An in vitro system of guinea pig pancreatic lobules convenient for the study of secretory processes is described in this paper. In this system: (a) the over-all glandular architecture of the tissue is preserved: lobules remain morphologically intact through 5 hours; (b) amylase discharge from unstimulated lobules is low (similar to 4%/hour) and linear over the 5 hours tested; (c) response to carbamylcholine chloride (10-5 M) is energy-dependent, rapid, and extensive (92% discharge of amylase by 5 hours); (d) initial rates of discharge remain stable over the first 3 hours; and (e) no autoactivation of zymogens occurs in incubation medium or tissue. The activation of four zymogens, i.e. chymotrypsinogen, trypsinogen, and procarboxypeptidases A and B, was studied using the following criteria for optimal activation: (a) maximal activation attainable under experimental conditions; (b) stability at the level of maximal activation; and (c) linear relationship between amounts of protein activated and enzyme activity elicited by activation. The concentration of activators (trypsin or enterokinase) and secretory protein, the presence or agents (bovine plasma albumin or Triton X-100) which minimize adsorptive losses of secretory protein on glass or plastic surfaces, and the temperature at which activation is carried out were found to be critical and different for each of the zymogens tested. The kinetics of the appearance of three enzyme activities (amylase, lipase, and ribonuclease) and four potential proteolytic activities (chymotrypsinogen, trypsinogen, and procarboxypeptidases A and B) into the incubation medium was studied under different conditions; i.e. rest and stimulation with various secretogogues (carbamylcholine chloride, caerulein, and pancreozymin). All seven activities estimated to represent similar to 75% of the secretory protein output of the exocrine pancreas were discharged in synchrony and in constant proportions and were released from the tissue to the same extent under each experimental condition investigated.

Microcirculation of the normal and inflamed canine pancreas.

Pancreas of normal dogs and the inflamed gland of experimental pancreatitis were studied by intra-arterial injection of Microfil, a silicone-rubber compound especially suited for study of the microcirculation. Duodenal vasculature and lobular vessels of the pancreas were studied as were those supplying the duct. Inter-lobular vessels were well visualized in the normal pancreas and intralobular vessels formed a fine reticular pattern throughout the cleared lobules. A complex network of vessels in the pancreatic duct was observed using this technique, apparently derived from the interlobular vessels. The blood supply of each layer of the duodenum was evaluated. Intraductal trypsin injection produced focal areas of pancreatitis associated with edema, poor vascular filling and spastic changes of the lobular vessels. Extravasation of Microfil, although not apparent on normal specimens, was prominent in inflamed specimens and suggested vascular weakness and disruption. Pancreatic lobules adjacent to inflammatory areas showed definite evidence of dilatation. The inflamed pancreatic ducts were markedly edematous, thickned, and showed incomplete vascular filling. When the duodenum adjacent to pancreatitis was injected with Microfil, edema and vasoconstriction were especially prominent in the duodenal muscular layer.

Studies on intracellular transport of secretory proteins in the rat exocrine pancreas

The effects of cobalt and lanthanum on the secretory process of the rat exocrine pancreas was studied in vitro using isolated pancreatic lobules. Cobalt in concentrations between 10(-3) to 10(-5) M has no effect on the rate of protein synthesis, intracellular transport, or discharge of zymogen granules, if the total population of stored granules is considered. It has, however, a marked effect on the release of newly packed zymogen granules which are formed during incubation in 10(-3) M CoC1(2). Determination of specific radioactivity in amylase released under the stimulation of 5X10(-6) M carbamylcholine and of total proteins retained in the zymogen granule fraction during stimulation indicate that granules formed during incubation in CoC1(2) are excluded from discharge. Lanthanum, on the other hand, has a differential effect on protein synthesis, intracellular transport, and discharge. Incorporation of tritiated leucine into TCA-precipitable proteins is inhibited by 50% at 10(-3) M LaC1(3). Intracellular transport as studied by cell fractionation is not changed during the first 35 min post pulse but is delayed from then on. This late effect is more pronounced if pancreatic lobules are preincubated for 60 min in 10(-3) M LaC1(3). Discharge of amylase and newly synthesized proteins is inhibited dose-dependently up to 80% by 10(-3) M LaC1(3). The effects of both cobalt and lanthanum are not due to an inhibition of cellular respiration. Comparison of these results with the inhibitory action of antimycin A between 10(-4) to 10(-8) M concentrations reveals a dose-dependent diminution of the rate of protein synthesis and intracellular transport, while discharge of granules is less energy dependent. The fine structural appearance of pancreatic lobules after 3 hrs incubation in 10(-3) M CoC1(2) is not altered, while in 5X10(-3) and 10(-3) M lanthanum acinar lumina are enlarged and the apical cytoplasm contains large vacuoles. At the highest concentration of lanthanum a flocculent electron dense material is observed apposed to the external lamina of the plasma membrane. The distribution of this material on the membrane is described. Antimycin A leads to cellular changes corresponding to the irreversible inhibition of cellular respiration. It is concluded from the results that cobalt acts on the process of granule formation inside the cell, while lanthanum by its binding to the plasma membrane may alter molecules involved in secretagogue binding and transport systems into the cell.

Studies on intracellular transport of secretory proteins in the rat exocrine pancreas. II. Inhibition of antimicrotubular agents.

The possible role of microtubules and microfilaments in the secretory process of the rat exocrine pancreas was analysed in vitro using isolated pancreatic lobules. Colchicine and vinblastine as microtubule inhibitors, hexylene glycol as a microtubule stabilizer, and cytochalasin B as a disruptive agent for microfilaments were used in increasing concentrations to test their effects on protein synthesis, intracellular transport, zymogen discharge, and cellular respiration. Colchicine only at 10(-2) M concentrations inhibits protein synthesis, while vinblastine inhibits at 10(-6) and 10(-5) M by 20% and at 10(-4) M by 55%. A similar inhibition is observed with 1.5% concentrations of hexylene glycol while cytochalasine B at 1,5 and 10 mug/ml is without effect on protein synthesis. Colchicine and vinblastine have their major effects on intracellular transport both in secretion studies and cell fractionation experiments. Colchicine in concentrations between 10(-3) to 10(-5) M inhibits discharge of newly synthesized proteins by 50%, while vinblastine shows a dose-response relationship of 40% inhibition of 10(-6) M to 90% at 10(-4) M. Discharge of amylase is uniformly reduced by 30% by both colchicine and vinblastine in the whole dose range. The pronounced effect of colchicine and vinblastine is evident in cell fractionation studies: both drugs inhibit the disappearance of protein radioactivity from microsomes and its appearance in zymogen granules; similarly the peak radioactivity in smooth microsomes (Golgi) appears delayed. No differential effect on the secretory process was observed with 1.5% concentrations of hexylene glycol or cytochalasin B at 1.5 and 10 mug/ml concentrations. A fines tructural analysis of microtubules and microfilaments in the exocrine pancreatic cell reveals their distribution in all parts of the cytoplasm and in relation to all cell organelles. Both systems (microtubules, microfilaments) seem to be connected, at least in certain areas of the cytoplasm and at the plasma membrane. The reduction of transport efficiency by microtubule inhibitors results in a deposition of secretory material in the cristernal space of the rough endoplasmatic reticulum, which leads to the formation of paracrystals. Colchicine at 10(-3) M concentrations leads to an enlargement of condensing vacuoles in the Golgi complex.

Studies on the Guinea Pig Pancreas: FRACTIONATION AND PARTIAL CHARACTERIZATION OF EXOCRINE PROTEINS

Abstract The protein mixture discharged by guinea pig pancreatic lobules incubated in vitro has been analyzed by two complementary techniques: isoelectric focusing (which separates proteins according to charge), and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (which separates proteins according to size). Isoelectric focusing columns spanning a set of pH ranges were used to fractionate secretory proteins biosynthetically labeled with 3H- or 14C-amino acids. Effluent fractions were used to determine radioactivity distribution and to locate (by specific enzyme assays) ribonuclease, amylase, chymotrypsinogen, trypsinogen, procarboxypeptidase A and procarboxypeptidase B either directly or after trypsin activation. There are single species of the first four proteins all of which are isoelectric above pH 9.2, and two forms of each procarboxypeptidase isoelectric near pH 5 (procarboxypeptidase A) and pH 7 (procarboxypeptidase B). The average isoelectric point of secretion mass-labeled with a mixture of 15 14C-amino acids is at pH 9.2. The most acidic species isoelectric near pH 3.4 can be labeled with both 35SO42- and amino acids. Its charge complementarity with the bulk of the secretory proteins is discussed with reference to the concentration and packaging of secretory proteins in the condensing vacuoles of the acinar cells. Sodium dodecyl sulfate-polyacrylamide gels resolve eight major proteins from the secretion. Six of these have been identified by cross-referencing aliquots from the isoelectric focusing columns onto the gels. No enzyme activities or potential activities have been assigned to two of the major proteins: the first has a molecular weight of 68,000 and the second appears to be slightly smaller than chymotrypsinogen. The results indicate that the guinea pig pancreas produces essentially the same complement of enzymes and zymogens as found in other species; they also demonstrate that the zymogen granules of the acinar cells contain the same proteins as the secretion discharged by pancreatic lobules upon carbamylcholine stimulation. The procedures described can be used to analyze on a protein-specific basis a variety of events in the secretory process.

Influence of cadmium ions on contractile response of isolated aortas to stimulatory agents.

Influence of cadmium ions on contractile response of isolated aortas to stimulatory agents.

The arteries of the pancreas of the dog. An injection–corrosion and microangiographic study

AbstractThe ramification of the pancreatic arteries, including the lobular vessels, was studied in 36 mongrel dogs by means of plastic injection and corrosion, as well as microangiography.The left pancreatic lobe receives the left cranial pancreatic artery and other smaller branches from the splenic artery, and two to four twigs from the gastroduodenal artery. In addition, it receives very often a branch from the common hepatic artery. Branches arising from the cranial mesenteric artery and from the first jejunal artery may also be found. The right cranial pancreatic artery and the right gastroepiploic artery give branches to the pancreatic angle. The arteries to the right pancreatic lobe arise from the cranial and from the caudal pancreaticoduodenal arteries.The interlobular arteries give origin to the intralobular arteries. The penetration and the distribution of the latter vessels differ in lobules of different shape. The intralobular course may be straight or curved. Branches arise generally at acute angles, forming Y or fork‐like patterns, ending into bundles of arterioles.

Two-stage procedure for total pancreatectomy in the rat.

A method is described for pancreatectomizing rats in two stages. In the first, most of the gland is excised, including the difficult to remove pancreatic lobes along the bile duct. A small portion, sufficient to prevent the appearance of diabetes, is left near the spleen. In the second stage, performed several weeks later, the remaining pancreas is extirpated rapidly, with minimal surgical trauma and immediate onset of severe diabetes. The time course of the changes in the levels of blood glucose, plasma free fatty acids, acetoacetate and triglycerides within the first twenty-four hours after the operation was studied. The results show that this preparation is very suitable for studying the metabolic effects of acute insulin deprivation in the rat.

The development and structure of the choledocho-duodenal junction in Balaenopteran whales.

AbstractThree specimens from Balaenopteran whales have been available for study: a 20 mm embryo, a fetus 57 inches long and the ampulla duodeni of a 47‐foot adult. By reconstruction, dissections and histological preparations, it has been possible to show that the extrahepatic portion of the bile duct is really an elongated hepato‐pancreatic duct receiving ductules draining both rostral and caudal pancreatic lobes. After coursing through the pancreas, this duct pierces the intestinal muscle at the beginning of the pars descendens duodeni, then runs through the whole length of the longitudinal fold before emptying at the bottom of the pars descendens. In the adult, maceration methods have demonstrated that there is no vestige at all of a sphincter of Oddi. Presumably, this is a consequence of the absence of the gall bladder. Contrary to statements in the literature, a complete foramen epiploicum, vestibule and lesser peritoneal sac could be demonstrated as well as a long infracardiac bursa. Most interesting is the presence of a sizable valve in the portal vein at the point where it enters the liver.