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Biomedical subjects

L Orci

Publications and source records attributed to L Orci.

At least 451 records · Page 25Linked to original sources
PubMed1976

Effects of insulin, glucagon, and epinephrine on the plasma membrane of the white adipose cell: a freeze-fracture study.

A quantitative study of the adipocyte plasma membrane under the influence of lipipolytic or lipogenic hormones has been carried out by freeze-fracture. The number of plasma membrane invaginations (so-called pinocytosis) and of intramembranous particles was evaluated. Under the influence of either insulin, glucogon, or epinephrine, the membrane invaginations were significantly increased with respect to control adipocytes. Insulin was shown to increase the number of intramembranous particles of the plasma membrane whereas glucagon or epinephrine had an opposite effect. These data point to a hormonal modulation of the fine-structural organization of the adipocyte plasma membrane.

Adipose Tissue↗
PubMed1975

Functional subdivision of islets of Langerhans and possible role of D cells.

Immunocytochemical examination of the islets of Langerhans in various animal species, including man, indicates that insulin-producing cells (B cells), glucagon-producing cells (A cells), and cells producing somatostatin or a somatostatin-like peptide (D cells) are not randomly arranged within the islet. Whenever A cells are found in the islet--i.e., mostly in its peripheral part--they are accompanied by D cells. However, most B cells, which occupy a central position, are in contact only with other B cells. In view of the inhibitory effect of somatostatin on both insulin and glucagon secretion, it is suggested that the arrangement of A, B and D cells is important to the normal and pathological functioning of the islet.

Animals↗
PubMed1975

Colchicine administration to mice: a metabolic and ultrastructural study.

A single injection of colchicine has been administered to normal albino mice, and the metabolic effects as well as the hepatic ultrastructural changes resulting from this treatment have been studied at various time intervals. A marked decrease in circulating triglyceride levels was evident 4 hours after colchicine injection and was maximum after 11 hours. It coincided with a marked increase in hepatic triglyceride content. Twenty hours after colchicine administration, plasma triglyceride levels and hepatic triglyceride content had returned to normal values. Similar changes in the levels of circulating proteins were observed although their magnitude was less than that observed for triglycerides. Ultrastructurally, colchicine treatment resulted in the virtual disappearance of the microtubules from the hepatocytes, and in the appearance of many clusters of vesicles containing very low density lipoprotein-like particles which eventually transformed into lipid droplets. These ultrastructural alterations were also completely reversible, the reversibility coinciding with the morphological reappearance of microtubules. Finally, colchicine treatment resulted in marked metabolic changes that are interpreted as representing an attempt, by the organism, to keep adequate energy sources during the period of lack of circulating triglycerides.

Amino Acids↗
PubMed1975

Exocrine pancreas: evidence for topographic partition of secretory function.

The pattern of amylase, lipase, and chymotrpsinogen content found in pancreatic exocrine tissue surrounding the islets of Langerhans (periinsular halos) differs from that of the rest, or teleinsular part, of the pancreas. Such a topographic partition of secretory function may play a role in the regulation of pancreatic juice composition.

Amylases↗
PubMed1975

Patterns of membrane organization in toad bladder epithelium: a freeze-fracture study.

Two cell-types of toad bladder epithelium show uncommon plasma membrane organization in freeze-fractured specimens. One type, the granular cell, contains a plasma membrane in which the A-face is poorly particulate luminally while the B-face discloses multiple large particles at this site. In contrast, the lateral and basal portions of the granular-cell membrane are typical in that more particles occupy the A-face than the B-face. In the other cell-type, which is mitochondria-rich, the plasma membrane, luminally, laterally, and basally, contains rod-shaped and a few globular particles in the A-face. We suggest that these two peculiar membrane organizations be considered in the localization of both vasopressin and aldosterone action in toad bladder.

Animals↗
PubMed1975

Glucagon: role in the hyperglycemia of diabetes mellitus.

Glucagon suppression by somatostatin reduces or abolishes hyperglycemia in dogs made insulin-deficient by somatostatin, alloxan, or total pancreatectomy. This suggests that the development of severe diabetic hyperglycemia requires the presence of glucagon, whether secreted by pancreatic or newly identified gastrointestinal A cells, as well as a lack of insulin. Glucagon suppression could improve therapeutic glucoregulation in diabetes.

Animals↗
PubMed1975

The essential role of glucagon in the pathogenesis of diabetes mellitus.

The following evidence suggests that diabetes mellitus may not be the simple consequence of relative or absolute insulin deficiency by itself, but may require the presence of glucagon: (1) relative or absolute hyperglucogonaemia has been identified in every form of endogenous hyperglycaemia, including total pancreatectomy in dogs; (2) insulin lack in the absence of glucagon does not cause endogenous hyperglycaemia, but when endogenous or exogenous glucagon is present, it quickly appears, irrespective of insulin levels at the time. These facts are compatible with a bihormonal-abnormality hypothesis, which holds that the major consequence of absolute or relative insulin lack is glucose underutilisation and that absolute or relative glucagon excess is the principal factor in the over-production of glucose in diabetes.

Alanine↗
PubMed1975

An apparent abnormaltiy of the B-cell microtubular system in spiny mice (Acomys cahirinus).

The pancreatic B-cell contains microtubules, which are thought to participate in the process of insulin release. In order to disclose a possible abnormaltiy of this B-cell microtubular system in animals with islet dysfunction, isolated islets from normal rats and mice, as well as from diabetic mutant mice (DBM mice) and from spiny mice (Acomys cahirinus) were incubated in the presence of vincristine, which causes the precipitation of the microtubular protein into paracrystalline deposits. Ultrastructural examination of the islets indicated that the volume-density of vincristine-induced deposits was markedly reduced in B-cells of spiny mice, when compared to that found in normal rats and mice and DBM mice. Exposure of the islets from spiny mice to a high glucose concentration, concomittantly to vincristine, caused a further reduction in vincristine-induced crystals content of the B-cell. It is speculated that an impairment of the B-cell microtubular system may account for the deficiency of insulin release found in spiny mice.

Animals↗
PubMed1975

Evidence for the D-cell of the pancreas secreting somatostatin.

By immunofluorescence, somatostatin-, glucagon- and insulin-containing cells are localized in serial sections of the pigeon pancreas. The distribution of the somatostatin immunofluorescent-cells corresponds to that of the D-cells (A1-cells), which are particularly numerous in this animal species. This observation, coupled with the finding of D, A and B-cells at the ultrastructural level, indicates that the D-cell is responsible for the secretion of somatostatin.

Animals↗
PubMed1975

Release of growth hormone from ox pituitary slices after pronase treatment.

Proteolytic enzymes have been used both to modify properties of the cell membrane and to dissociate cells from many tissues including pituitary (4, 5, 12). Exposure of secretory tissues to pronase can alter their secretory response. Thus incubation of pancreatic islets of Langerhans in the presence of low concentrations of pronase increased the subsequent release of insulin in the presence of stimulatory and nonstimulatory glucose concentrations (7). The purpose of the present investigation was to determine whether low concentrations of pronase have the same stimulatory effect on the release of a pituitary hormone, growth hormone. Such an effect on hormone release could be of some importance in view of the development of dissociated cell systems as models for the study of the control of hormone release (4, 5).

Animals↗
PubMed1975

Colchicine-binding protein of the liver. Its characterization and relation to microtubules.

Colchicine-binding activity of mouse liver high-speed supernate has been investigated. It has been found to be time and temperature dependent. Two binding activities with different affinities for colchicine seem to be present in this high-speed supernate, of which only the high-affinity binding site (half maximal binding at 5 x 10(-6) M colchicine) can be attributed to microtubular protein by comparison with purified tubulin. Vinblastine interacted with this binding activity by precipitating it when used at high concentrations (2 x 10(-3) M), and by stabilizing it at low concentrations (10(-5) M). Lumicolchicine was found not to compete with colchicine. The colchicine-binding activity was purified from liver and compared with that of microtubular protein from brain. The specific binding activity of the resulting preparation, its electrophoretic behavior, and the electron microscope appearance of the paracrystals obtained upon its precipitation with vinblastine permitted its identification as microtubular protein (tubulin). Electrophoretic analysis of the proteins from liver supernate that were precipitated by vinblastine indicated that this drug was not specific for liver tubulin. Preincubation of liver supernate with 5 mM EGTA resulted in a time-dependent decrease of colchicine-binding activity, which was partly reversed by the addition of Ca++. However, an in vitro formation of microtubules upon lowering the Ca++ concentration could not be detected. Finally, a method was developed enabling that portion of microtubular protein which was present as free tubulin to be measured and to be compared with the total amount of this protein in the tissue. This procedure permitted demonstration of the fact that, under normal conditions, only about 40% of the tubulin of the liver was assemled as microtubules. It is suggested that, in the liver, rapid polymerization and depolymerization of microtubules occur and may be an important facet of the functional role of the microtubular system.

Animals↗
PubMed1975

In vivo assembly of tight junctions in fetal rat liver.

Examination of glutaraldehyde-fixed, freeze-fractured livers from 14-15-day rat fetuses provided the basis for the following observations. Membrane particles align in otherwise poorly particulated areas of the presumptive pericanalicular plasma membrane (A face), frequently forming a discontinuous "honey-comb" network joining small particle islands. Even at this early stage, contiguous B-fracture faces contain furrows, rather than rows of pits, distinguishing the linear particle aggregates on the A face as developing tight junctions rather than gap junctions. Short segments of these linear arrays merge with smooth ridges clearly identifiable as segments of discontinuous tight junctions. With the continuing confluence of particulate and smooth ridge segments, mature tight junctions become fully appreciable. We conclude that tight junctions form de novo by the alignment and fusion of separate particles into beaded ridges which, in turn, become confluent and are transformed into continuous smooth ones. At 21 days of fetal life, most of the images of assembly have disappeared, and the liver reveals well-formed bile canaliculi sealed by mature tight junctions.

Animals↗
PubMed1975

Identification of glucagon in the gastrointestinal tract.

Gel filtration studies on Bio-Gel P-10 columns of a 50-fold purified porcine duodenal extract revealed a main peak of glucagon-like immunoreactivity (GLI) in the 2,900 mol wt zone and a smaller peak in the 3,500 mol wt zone, the same zone as the pancreatic glucagon marker. Like pancreatic glucagon, samples of 3,500 mol wt material gave essentially identical measurements in radioimmunoassays employing the pancreatic glucagon-specific antiserum 30K and the GLI crossreacting antiserum 78J, whereas the 2,900 mol wt peptide gave 60-fold higher readings in the 78J assay. On disk gel electrophoresis, the 3,500 mol wt fraction, like pancreatic glucagon, migrated at pH 8.3, whereas the 2,900 mol wt peptide remained at the origin; at pH 4.7, the 2,900 mol wt peptide migrated while the 3,500 mol wt immunoreactive peptide and glucagon remained at the origin. Isoelectric focusing revealed the 3,500 mol wt moiety to have an isoelectric point (pI) of 6.2, the same as pancreatic glucagon, whereas the 2,900 mol wt peptide had an pI greater than 10. The glycogenolytic activity of the 3,500 mol wt peptide in the perfused rat liver did not differ significantly from glucagon, and its adenylate cyclase stimulating activity in partially purified liver cell membranes was comparable to that of glucagon; the 2,900 mol wt peptide had less than 20% of these activities. In samples of 3,500 mol wt material subjected to isoelectric focusing, adenylate cyclase-stimulating activity was confirmed to fractions containing 30K immunoreactivity with a pI of 6.2. In samples of 2,900 mol wt material subjected to isoelectric focusing, adenylate cyclase-stimulating activity was confined to fractions containing 78J immunoreactivity with an pI greater than 10. Displacement of [125-I]glucagon from the membranes was limited to these two biologically active fractions. However, the affinity of both pancreatic glucagon and the 3,500 mol wt peptide was an order of magnitude greater than of the 2,900 mol wt peptide. Thus, by all of several biologic, physiocochemical, and immunometric techniques, the 3,500 mol wt gut immunoreactive peptide could not be distinguished from pancreatic glucagon, while the 2,900 mol wt peptide was readily differentiated by all these techniques. "True" A-cells, ultrastructurally indistinguishable from pancreatic A-cells but differing from the A-like cells of the lower bowel, were identified in the gastric fundus of dogs. Their distribution corresponded to that of the 3,500 mol wt immunoreactivity resembling pancreatic glucagon, while the distribution of "A-like cells" in the lower small intestine corresponded to that of GLI.

Adenylate Kinase↗
PubMed1975

A morphological basis for intercellular communication between alpha- and beta-cells in the endocrine pancreas.

By degranulating beta-cells in the islets of Langerhans of the rat with sulfonylurea, it has been possible to distinguish unambiguously alpha-cells from beta-cells in freeze-fracture replicas. In such preparations, we found morphologically typical tight and gap junctions occurring between alpha- and beta-cells. The presence of gap junctions offers indirect evidence that these cells are coupled with one another; coupling may influence the secretory behavior of alpha- and beta-cells maintaining glucose homeostasis within tightly constricted limits.

Animals↗