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Biomedical subjects

L Orci

Publications and source records attributed to L Orci.

At least 415 records · Page 23Linked to original sources

Pore-like structures in biological membranes.

In freeze-fracture replicas, biological membranes appear as smooth surfaces interrupted by random globular protrusion, the intramembrane particles. Smooth areas correspond to the membrane phospholipidic domain, while intramembrane particles are the morphological counterpart of membrane proteins. In the present work, examination of membranes in a variety of cell types reveals that a number of intramembrane particles contain an electron-dense spot. The spot is thought to correspond to a minute pit in the particle, filled by the platinum used in the freeze-fracture procedure. Similar images, described previously in intramembrane particles forming the specific array of the gap junction, were interpreted as hydrophilic channels bridging the interior and the exterior of the plasma membrane. Comparison between the gap junction particles and the non-junction particles containing a dense spot suggests that these latter may too contain hydrophilic channels. The channels in random intramembrane particles would represent the morphological counterparts of the water-filled pores described in models of membrane permeability.

Animals↗

Possible roles of the pancreatic D-cell in the normal and diabetic states.

The A-, D-, and B-cells--the islet cells that contain, respectively, immunoreactive glucagon, somatostatin, and insulin--are distributed within a specialized heterocellular region of the islets of Langerhans as if to permit heterologous contacts between all three cell types. Inasmuch as each one of the three secretory products of these three cell types influences the secretion of at least one of its neighboring cells, "paracrine" influence on islet hormone secretion becomes a reasonable hypothesis. Glucagon stimulates both insulin and somatostatin release, while insulin and somatostatin both inhibit glucagon release, providing the basis for a feedback relationship through which A-cell secretion may be restrained. In addition, glucagon-mediated insulin secretion may be estrained by glucagon-stimulated somatostatin release. Such intercellular relationships could help determine the composition of the insulin and glucagon mistures released within a given metabolic setting.

Diabetes Mellitus↗

Role of glucagon in diabetes.

The glucagon-secreting A cell is a vital component of the organ system which regulates the distribution of fuel--the islets of Langerhans. Bihormonal control of glucoregulation through a push-pull system maintains the glucose concentration of extracellular fluid within narrow limits irrespective of glucose flux rates through relative equality of glucose influx and efflux. This equality requires appropriate secretion mixtures of the biologic antagonists, insulin and glucagon, directed by a glucose sensor. In severe diabetes, there are virtually no B cells and A cells are in contact largely with other A cells and their glucose-sensing capacity is lost. The A cell hypersecretes and in most juvenile type diabetics aggressive therapy with insulin fails to restore it to normal. Glucagon is a factor in the development of endogenous hyperglycemia, and ketoacidosis. Its suppression may provide a possible approach in the future pharmacologic management of diabetic hyperglycemia.

Antigens↗

Perturbation of the adipose cell plasma membrane in obese (ob/ob) mice.

The plasma membrane organization of adipocytes of genetically obese (ob/ob) mice has been studied by freeze-fracture and compared to that of control (lean) mice and of small and large adipocytes in rats of different age. The large size increase of ob/ob adipocytes is accompanied by a decrease in the concentration of surface invaginations and of intramembrane particles in the plasma membrane as compareed to control, nonobese mice. By contrast, the membrane of large adipocytes of normal old rats has a concentration of invaginations and particles similar to that present in the membrane of small adipocytes of young rats. Thus, the changes of the plasma membrane organization in ob/ob adipocytes seems not to be due to size increase only but may reflect a more general perturbation of the membrane, such as evidenced by the reduced insulin and lectin binding capacity demonstrated in these cells.

Adipose Tissue↗

[Ultrastructural changes in the organization of plasma membranes in adipocytes of obese mice (ob/ob)].

Freeze-fracture replicas were obtained from adipocytes in control and obese (ob/ob) Mice. Quantitative evaluation of the replicas shows that plasma membranes of adipocytes in ob/ob Mice have 50% less intramembrane particles than plasma membranes in control Mice. Since intra-membrane particles represent, at least in part, the proteins of the membrane, this suggests a decreased protein concentration, as well as a perturbed protein-lipid ratio in adipocyte membranes of obese Mice.

Adipose Tissue↗

[Pancreatic polypeptide islets and glucagon islets : distinct topographic distribution in rat pancreas].

The immunocytochemical technique for the cellular localization of hormones allows a precise identification of islet cell types responsible for the production of insulin, glucagon, somatostatin and pancreatic polypeptide. A systematic study of Rat pancreas has revealed a hitherto undescribed morphological heterogeneity of islets. In fact, the cellular composition of islets differs according to their anatomical distribution. The "PP islets" are preferentially located in the inferior 2/3 of the head of the pancreas, whilst "glucagon islets" populate the remainder of the gland.

Animals↗

Immunofluorescent localization of secretin in pancreatic monolayer culture.

Immunofluorescent cells to synthetic secretin were identified in monolayer culture of neonatal rat pancreas. No cross reaction of anti-secretin was observed with either glucagon, somatostatin or gastrin. The presence of cells containing secretin or a secretin-like peptide adds a new cell type to the three already characterized (insulin, glucagon and somatostatin containing cells) in monolayer culture.

Animals↗

Secretory processes, carbohydrate and lipid metabolism in isolated mouse hepatocytes. Aspects of regulation by glucagon and insulin.

The procedure of Berry and Friend for isolation of intact hepatocytes has been adapted to mouse livers. The ultrastructure of these cells was satisfactorily preserved. Isolated mouse hepatocytes secreted proteins and triacylglycerols. These secretory processes were inhibited by colchicine, indicating a likely involvement of the microtubular system for their normal occurrence. Ultracentrifugation of medium incubated with hepatocytes, followed by electrophoresis and electron microscopic examination of the floating fraction (density less than 1.006) allowed to conclude that secreted triacylglycerols were very low density lipoproteins. Glycogenolysis and lipogenesis were stimulated or inhibited, respectively, by low concentrations of glucagon (10(-10) M). Other metabolic parameters were influenced by the hormone but were less sensitive to its action. Inhibition of lipogenesis by glucagon was associated with a decrease in acetyl CoA carboxylase activity. This decrease does not appear to be related to intracellular fatty acyl-CoA accumulation secondary to hepatic lipase activation by the hormone. Insulin was effective alone or counteracted glucagon effects on lipogenesis or glycogenolysis only when exposure of cells to collagenase was held minimal. This suggests that, during isolation of hepatocytes, insulin receptors may, for unknown reasons, be more fragile than those of glucagon.

Acetates↗

Modifications in the release of rat growth hormone in vitro and the morphology of rat anterior pituitaries incubated in various ionophores.

The ionophore A23187 increased the release of rat growth hormone in the presence of a phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine; a second ionophore X537A inhibited growth hormone release induced by the methylxanthine. A23187 did not alter rat growth hormone release in the absence of 3-isobutyl-1-methylxanthine, but X537A enhanced hormone release in the absence of calcium or in the presence or somatostatin. These findings provide further evidence that both calcium and cyclic AMP are important in the regulation of growth hormone release. Tissue incubated in X537A combined electronlucent vesicles apparently derived from the Golgi apparatus, swollen granules and mitochondria with dense matrices. Tissue incubated in the presence of valinomycin or A23187 did not show altered morphology of either secretory granules or the Golgi complex. Possible mechanisms of these changes are discussed.

3',5'-Cyclic-AMP Phosphodiesterases↗

[Immunocytochemical identification of the glucagon-secreting cells in gastric mucosa].

Immunocytochemical investigations at the light and electron microscope level, using specific antiglucagon serum, revealed in the gastric oxyntic mucosa of the Dog, the presence of positive cells, undistinguishable ultrastructurally from pancreatic A-cells. No positive reaction was detected in any other gastrointestinal segment. These results suggest that gastric A-cells are responsible for the secretion of gastric glucagon.

Animals↗

Membrane topology as revealed by the binding of macromolecules.

Binding sites for specific molecules at the cell surface can be localized with the electron microscope in thin-section, freeze-etch and shadow-casting preparations. The receptors tested were binding sites to concanavalin A (Con A) labelled with haemocyanin and binding sites to insulin labelled with ferritin. Con A-binding sites were localized in endocrine cells of the pancreas and insulin-binding sites in isolated liver plasma membranes. The relevance of the topographical distribution of the binding sites to cell membrane organization is discussed.

Animals↗