Biomedical subjects
L Orci
Publications and source records attributed to L Orci.
Junctions in developing human and rat kidney: a freeze-fracture study.
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The microanatomy of the islets of Langerhans.
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Stimulation of pancreatic immunoreactive somatostatin (IRS) release by glucagon [proceedings].
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Some aspects of the morphology of insulin-secreting cells.
By using a spectrum of microscopical techniques such as thin sectioning, autoradiography, cytochemistry and freeze-etching, it is possible to unravel the main cytological events associated with synthesis, intracellular transport, storage and discharge of the hormone insulin by B-cell of the islet of Langerhans.
Hypertrophy and hyperplasia of somatostatin-containing D-cells in diabetes.
Insulin-, glucagon-, and somatostatin-contianing cells, identified by immunofluorescent staining, were quantitated morphometrically in sections of pancreas obtained from diabetic and nondiabetic humans and rats. Both the volume density and number of somatostatin- and glucagon-containing cells were significantly increased in the islets of juvenile-type human diabetics and of streptozotocin diabetic rats.
In vivo induction of tight junction proliferation in rat liver.
The chronic administration of phalloidin induces an extensive development of tight junctions between rat hepatocytes. The junctional strands lose their predominantly parallel orientation with respect to the canalicular lumen and extend abluminally in irregular patterns which cover large membrane areas at considerable distance from the bile canaliculi. These changes indicate both proliferation and provide further evidence that these junctions are not permanent differentiations of the cell membrane.
Morphological changes in tight junctions of Necturus maculosus proximal tubules undergoing saline diuresis.
Tight junctions between epithelial cells are believed to control the paracellular diffusion of substances across epithelia. Epithelia in which tight junctions are poorly developed display a higher paracellular electrical conductance, while those with extensive tight junctions show lower conductance values. We described here a particular epithelium, that of the proximal tubules of the Necturus kidney, in which the development of the tight junctions varies in parallel with a change of paracellular electrical conductance. In control conditions, tight junctions between epithelial cells of the proximal tubules are more developed than in tubules undergoing saline diuresis, a situation which increases the conductance across the paracellular shunt pathway.
Identification of glucagon-producing cells (A cells) in dog gastric mucosa.
An immunocytochemical technique using specific antiglucagon serum reveals the presence of glucagon-containing cells situated exclusively in the oxyntic glandular mucosa of the dog stomach. Electron microscope examination of the mucosa demonstrated endocrine cells containing secretory granules with a round dense core surrounded by a clear halo, indistinguishable from secretory granules of pancreatic A cells. Like the alpha granules of pancreatic A cells, the granules of these gastric endocrine cells exhibited a peripheral distribution of silver grains after Grimelius silver staining. Moreover, the granules of these cells were found to be specifically labeled with reaction product, using the peroxidase immunocytochemical technique at the ultrastructural level. Accordingly, these cells were named gastric A cells. These data suggest that the gastric oxyntic mucosa contains cells indistinguishable cytologically, cytochemically, and immunocytochemically from pancreatic A cells. It is believed that gastric A cells are responsible for the secretion of the gastric glucagon.
Secretion-related uptake of horseradish peroxidase in neurohypophysial axons.
During secretion of the neurohypophysial hormones, oxytocin and vasopressin, secretory granule membrane is added to the plasma membrane of the axon terminals. It is generally assumed that subsequent internalization of this additional membrane occurs by endocytosis. In order to study this process, we have traced the uptake of intravenously injected horseradish peroxidase by neurohypophysial axons in rats and golden hamsters. Peroxidase reaction product within the secretory axons was found mainly in vacuolar and C-shaped structures of a size comparable with or larger than the neurosecretory granules. Our observations suggest that these large horseradish peroxidase (HRP)-impregnated vacuoles arise directly by a form of macropinocytosis. Morphometric analysis indicated that this form of membrane retrieval increased significantly after the two types of stimuli used, reversible hemorrhage and electrical stimulation of the pituitary stalk. Microvesicular uptake of HRP was found to be comparatively less.
Physiology and pathophysiology of glucagon.
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Morphology and metabolism of an aortic intima-media preparation in which an intact endothelium is preserved.
An in vitro preparation of rabbit aortic "intima-media" previously shown to exhibit stable rates of respiration and glucose metabolism and the high rate of aerobic glycolysis considered characteristic of the metabolism of this tissue was subjected to electron microscopic examination. In samples examined immediately after the aortae were dissected free of adipose tissue and adventitia, under conditions similar to those now in common use, marked and widespread alterations in endothelial cell structure were present, including loss of cell integrity. The vascular smooth muscle cells retained a normal electron microscopic (EM) appearance. During subsequent incubation with 5 mM glucose in Krebs-Ringer bicarbonate (KRB), pH 7.4, under the conditions usually employed in studies of this preparation, large zones of the luminal surface were rapidly denuded of endothelium, and the remaining endothelial cells exhibited a wide range of ultrastructural alterations. The smooth muscle cells, however, continued to maintain a normal EM appearance. A method was developed to prepare segments of rabbit aortic intima-media which retained an intact layer of endothelium resembling that observed in tissue fixed in situ. During a 1-h incubation with 5 mM glucose in KRB, pH 7.4, gas phase 5% CO2/95% O2, containing 6% bovine serum albumin, the intact aortic intima-media preparation retains an essentially unmodified EM appearance and exhibits linear rates of respiration. Under these conditions the intact aortic intima-media preparation exhibits significantly higher rates of O2 uptake and glucose uptake than those observed in our previous preparation or in other reported aortic intima-media preparations. The intact aortic intima-media does not exhibit the high rate of aerobic glycolysis during in vitro incubation that has been considered characteristic of the metabolism of rabbit, rat, and swine aortic intima-media. In addition, the magnitude of the Pasteur effect was far greater than that observed in other aortic intima-media preparations. The data suggest that component cells of the aortic intima-media may derive a major fraction of their energy requirements from respiration; they raise further questions concerning the significance of the high rate of aerobic glycolysis observed when aortic intima-media preparations are incubated in vitro, and they suggest that documentation of the EM appearance of the endothelium in such preparations is desirable.
Development of insulin and glucagon binding and the adenylate cyclase response in liver membranes of the prenatal, postnatal, and adult rat: evidence of glucagon "resistance".
Although plasma glucagon levels in the rat fetus are in the adult range, hepatic glycogen is present in far greater abundance in the fetus than in the adult. To explain this paradox, adenylate cyclase response to glucagon was studied in partially purified membranes of rat livers obtained throughout perinatal life and at 3 months of age. The adenylate cyclase response to glucagon (10(-9) M) was only 7% of the adult response at day 15 of fetal life and 20% on the 21st day. No until after the 30th day postpartum did not reach maturity. Yet, the adenylate cyclase response to stimulation by NaF was comparable to the adult response throughout fetal life. The binding of [125I]iodoglucagon (2 X 10(-9) M) by these membrane preparations was only 1% of the adult level at day 15 of fetal life and increased to 23% at the 21st day, and, like the adenylate cyclase response to glucagon, did not reach maturity until after the 30th day of postnatal life. In contrast, insulin binding on the 15th day of gestation was 11% of the adult level and on the 21st day 45% of the adult level, reaching adult levels by the 30th postnatal day. An increase in membrane-associated particles, reflecting intramembranous protein, was observed during prenatal life, but the mean particle number per mum2 reached adult levels on the 21st day of fetal life, indicating that subsequent changes in hormone binding were clearly independent of non-specific changes in the number of particles. The findings suggest that the fetal liver is less sensitive to glucagon action than the adult liver, and that this glucagon "resistance" is mediated by a reduced capacity of the hepatocyte to bind glucagon at a time when substantial binding of insulin is demonstrable. Selective discrimination against glucagon may be important in promoting the anabolic processes required for normal fetal development.
Gastric A-cell function in insulin-deprived depancreatized dogs.
To determine if gastric A-cells are a major source of the glucagonemia of insulin-deprived depancreatized dogs and to examine their secretory behavior, immunoreactive glucagon (IRG) was measured simultaneously in plasma from the inferior vena cava (VC) and from a gastric vein (GV) draining the fundus. Basal GV IRG averaged 205 +/- 35 pg/ml, significantly above the VC level of 71 +/- 30 (P less than 0.001) and rose to 1417 +/- 498 1.5 minutes after the start of an arginine infusion, exceeding VC IRG at all points (P less than 0.01). Measurement of IRG in gastric, jejunal, and ileal veins and vena cava revealed an IRG gradient only across the stomach. Measurement of glucagon-like immunoreactivity (GLI) revealed no gradient across the stomach, jejunum, or ileum, thus excluding cross-reaction with GLI as the cause of the GV hyperglucagonemia. Intragastric arginine elicited a near doubling of GV IRG within 1.5 minutes and this persisted for at least 120 minutes, ranging from 142 to 623 pg/ml above the VC level. Infusion of insulin at a physiologic rate lowered GV IRG from 665 +/- 66 to 151 +/- 49 pg/ml in 20 minutes and abolished the GV-VC gradient within 60 minutes, whereas intravenous and intragastric glucose administration without insulin did not alter GV IRG. It is concluded that: 1) in the insulin-deprived depancreatized dog, the stomach is a major source of IRG; 2) gastric IRG secretion is somehow stimulated by intravenous and intragastric arginine administration; 3) it is not influenced by intravenous or intragastric glucose administration; and 4) its release is suppressed by physiologic levels of insulin.
Decreased pancreatic somatostatin (SRIF) concentration in spontaneously diabetic mice.
Spontaneously diabetic C57BL/6J obob and C57BL/Ks dbdb mice have been shown to have significantly decreased immunoassayable pancreatic somatostatin concentrations compared to lean littermate controls at 11-12 weeks: obob 1.06+/-0.15 pg/mug protein (n=10) vs control 1.94+/-0.-6 pg/mug protein (n=10) (mean +/- SE; p less than 0.005); dbdb 0.7+/-0.2 pg/mug protein (n=8) vs control 1.5+/-0.2 pg/mug protein (n=8) (mean +/- SE; p less than 0.005). An inverse relationship between circulating insulin levels and pancreatic SRIF concentration is suggested.
Patterns of calcium localization in pancreatic endocrine cells.
Subcellular calcium localization in the dndocrine cells of rat pancreas was studied by the pyroantimonate precipitation technique. Calcium-containing electron-dense deposits in the endocrine cells were mostly found within secretory granules and along the plasma membrane, but their pattern of distribution in A-, B- and D-cells displayed qualitative and quantitative differences. In B-cells, numerous secretory granules contained deposits located in the halo surrounding the granule core. In A-cells, only few granules contained precipitates in their halo, whereas in D-cells, deposits were situated in the dense core of the secretory granules. Deposits along the plasma membrane occurred generally on the outer leaflet of the plasma membrane of B- and D-cells and on the inner leaflet of that of A-cells. In islets incubated at a high glucose concentration or in the presence of the calcium ionophore A23187, the number of beta granules containing precipitates was significantly increased. By contrast, only few deposits were observed in B-cells incubated in calcium-deprived medium enriched with EGTA. These findings indicate that: the pattern of calcium localization varies in different islet cell types; in B-cells the secretory granules represent one of the major stores of intracellular calcium; and that this store undergoes changes in conditions which alter insulin release.
A new look at the metabolism of the arterial wall.
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Islet cell membrane alteration by diabetogenic drugs.
Freeze-fracture of islets of Langerhans treated in vitro with diabetogenic agents alloxan and streptozotocin shows a decrease in the number of intramembranous particles of islet cell plasma membranes. This decrease is restricted to the membrane's A-fracture face and it can be prevented by experimental conditions which are known to counteract the toxic effect of both alloxan and streptozotocin.