Search PubMed⌕ Search

Biomedical subjects

L Orci

Publications and source records attributed to L Orci.

At least 289 records · Page 16Linked to original sources
PubMed1982

High somatostatin uptake by the isolated perfused dog pancreas consistent with "insulo-acinar" axis.

The canine pancreas takes up 50-80% of somatostatin perfused over a concentration range of 20 to 4000 pg/ml, compared to less than 21% of insulin or glucagon. This high uptake by acinar tissue of somatostatin, a potent inhibitor of acinar function, is compatible with a system for selective intrapancreatic control of exocrine pancreatic function via the insulo-acinar portal venous system.

Animals↗
PubMed1982

Glicentin precedes glucagon in the developing human pancreas.

A quantitative evaluation of immunofluorescence elicited by anti-insulin, anti-glucagon, anti-glicentin, anti-somatostatin and anti-pancreatic polypeptide antisera has been carried out in the pancreas of 5 human fetuses from 3.0 to 9.6 cm C.R. The data obtained indicate that while insulin and somatostatin-containing cells are approximately in similar proportions with respect to the other endocrine cell types in the five fetuses studied, the glucagon and glicentin immunoreactive cells and the pancreatic polypeptide cells are not : a) pancreatic polypeptide-containing cells increase in proportion as fetuses grow older; b) the youngest fetuses (3.0 to 4.3 cm C.R.) contain a high proportion of cells reacting to anti-glicentin antiserum only (GLI-cells) and a small proportion of cells stained both with the anti-glicentin and anti-glucagon antisera (GLI/GLU-cells). However, the latter cell type which stains similarly as the postnatal and adult pancreatic A-cell (GLI-cells are not detectable in the postnatal and adult pancreas) increases iin proportion in older fetuses, while the proportion of GLI-cells decrease. The data suggest that the definitive adult-type A-cell matures from a GLI-cell type which is not able to convert glucagon precursors GLI(s) into glucagon.

Female↗
PubMed1982

Effect of pH and lysosomotropic agents on membrane-associated and internalized 125I-iodinated human growth hormone in cultured human lymphocytes: a quantitative biochemical and electron microscopic study.

When 125I-iodinated human GH ([125I]iodo-hGH) interacts with cultured human lymphocytes at 15 C, the reaction is reversible, but at 37 C the reaction becomes less dissociable as a function of incubation time. Acidification of the incubation medium results in rapid ligand dissociation at 15 C, but at 37 C the acid-dissociable component decreases as a function of incubation time. Under conditions where approximately 50% of the ligand is internalized by the cell, 90% is nondissociable. When the 37 C incubation is carried out in the presence of 25 mM NH4Cl, cell-associated radioactivity is increased. Under these conditions approximately 90% of cell-associated radioactivity also is nondissociable. Using quantitative electron microscopic autoradiography, the proportion of [125I]iodo-hGH associated with the plasma membrane and internalized by the cell is indistinguishable in the presence or absence of NH4Cl. Irreversible [125I]iodo-hGH association with cultured human lymphocytes is due to time- and temperature-dependent effects in the plasma membrane of the cell. These effects cannot be distinguished from internalization by acidification. Furthermore, lysosomotropic agents increase cell-associated radioactivity, but the proportion internalized is not increased.

Ammonium Chloride↗
PubMed1982

New perspectives on the microvasculature of the islets of Langerhans in the rat.

The vasculature of the islets of Langerhans was studied in rats using methacrylate corrosion casts and islet reconstructions from stained serial paraffin sections. In corrosion casts, which allowed a three-dimensional view of the pancreatic vasculature, all islets had one or two afferent arterioles, which gave off numerous capillaries to form a glomerular-like network. Islets could be grouped in three classes on the basis of size. Moreover, these classes had preferential locations within the vascular tree: the smaller the islet, the more peripheral. In small islets (those less than 160 micrometers in diameter) efferent capillaries arose from this network and either coalesced at the periphery of the islet or passed through perinsular exocrine tissue before coalescing into venules. However, in intermediate islets (those 160--260 micrometers in diameter) and large islets (those greater than 260 micrometers in diameter) efferent capillaries usually coalesced at the edge of the islet forming an extensive fingerlike network of collecting venules over the islet. This suggested that at least in the rat a large amount of the islet tissue is directly drained by venules. In serial paraffin sections of islets perfused with India ink and stained alternately for B-cells or for non-B-cells, the relation of the blood vessels and the organized array of different cell types making up the islet was discernible. In islets of all sizes, the afferent arterioles entered the islet of all sizes, the afferent arterioles entered the islet at discontinuities of the mantle of non-B-(glucagon, somatostatin, and pancreatic polypeptide) cells. Entering at the B-cell mass, the arterioles broke into capillaries that traversed the B-cell core before passing through the opposite non-B-cell mantle. The afferent capillaries coalesced into collecting venules outside the islet. In intermediate and large islets, the overlying collecting venule network was closely apposed to the mantle. These anatomic findings indicate that in the rat islet only some of the efferent vessels are part of a insuloacinar portal system and that the afferent vessels reach the B-cell core without passing through the non-B-cell islet tissue.

Animals↗
PubMed1982

Direct demonstration of insulin receptor internalization. A quantitative electron microscopic study of covalently bound 125I-photoreactive insulin incubated with isolated hepatocytes.

When 125I-insulin is incubated with isolated rodent hepatocytes at 37 degrees C, the ligand initially binds to the plasma membrane of the cell and is subsequently internalized by adsorptive endocytosis. To confirm directly that the insulin receptor is internalized with the ligand, we covalently linked photoreactive 125I-N sigma B29 (azidobenzoyl) insulin to its specific hepatocyte receptor and followed its fate by quantitative electron microscopic autoradiography. We found that the covalently linked photoreactive insulin is internalized by the cell in fashion analogous to the internalization of ordinary 125I-insulin, indicating that, at least under these conditions, the insulin receptor is internalized with the ligand.

Animals↗
PubMed1982

Quantitation of endocrine cell content in the pancreas of nondiabetic and diabetic humans.

The application of immunofluorescence technique with anti-insulin, anti-glucagon, anti-somatostatin, and anti-pancreatic polypeptide (PP) antisera to sections of precisely sampled regions of the human pancreas allowed the quantitative evaluation of the total content of these four endocrine cell populations in 13 nondiabetics, in 2 insulin-dependent diabetics (IDDM), and in 2 non-insulin-dependent diabetic subjects (NIDDM) of various age and sex. In nondiabetic subjects, PP-cells appear sex-related. Male individuals have a significantly greater volume of PP-cells than female. In diabetic subjects, the only marked difference as compared with nondiabetics is the reduction of insulin cell volume in IDDM. Other small differences between individual endocrine cell volumes are detectable in both IDDM and NIDDM as compared with nondiabetics, but their significance is at present unclear. The qualitative changes of islet structure accompanying insulin cell reduction in IDDM were not considered in the present study.

Adolescent↗
PubMed1982

The role of glucagon in diabetes.

The current understanding of diabetes points to a bihormonal abnormality in which the level of glucagon is inappropriately high relative to the level (or activity) of insulin, causing a rate of hepatic glucose production that is high relative to glucose utilization. This imbalance can be corrected by increasing insulin or reducing glucagon. At the present time only the former approach constitutes a feasible and practical means of managing the diabetic patient. Whether or not concomitant suppression of glucagon will provide a further therapeutic advantage remains to be determined.

Blood Glucose↗
PubMed1982

Distribution of intramembrane particles and filipin-sterol complexes in plasma membranes of kidney. I. Corpuscle of Malpighi.

A quantitative study was performed on glomerular cell types from the rat kidney freeze fractured after conventional fixation or following exposure to the sterol-specific antibiotic, filipin. The results reveal a considerable variation on the size and number of intramembrane particles, as well as in the number of filipin-sterol complexes present on plasma membranes of the different cell types present in the glomerulus. These differences in membrane structure probably reflect specialized functions of the individual plasma membranes within the glomerulus. The most striking observation, however, was the low particle content and poor filipin labeling of podocyte foot process bases (which lie against the basal lamina) compared with the rest of the podocyte plasma membrane. The presence of distinct membrane domains in podocytes may be a factor involved in maintaining their specific architecture that is critical for the normal functioning of the kidney filtration barrier.

Animals↗
PubMed1981

Topology of morphologically detectable protein and cholesterol in membranes of polypeptide-secreting cells.

The freeze-fracture morphology of intracellular and plasma membranes in endocrine and exocrine polypeptide-secreting cells has been studied to detect changes while these membranes interact during secretion. A qualitative and quantitative evaluation of intramembrane particles and filipin binding as indicators of protein and cholesterol content of the membranes, respectively, reveals the following changes. From the forming of the maturing pole of the Golgi complex, membranes lose morphologically detectable protein and gain morphologically detectable cholesterol. The protein-poor, cholesterol-rich secretory granule membrane then interacts with a richly particulate plasma membrane in endocrine cells and with a moderately particulate luminal membrane in exocrine cells. The site of interaction between secretory granule and plasma membrane is characterized by a local clearing of intramembrane particles; by contrast, filipin-binding sites revealing cholesterol are present in this area. In exocrine cells, the fused secretory granule, which is initially rich in filipin-cholesterol complexes and poor in particles, appears to lose progressively its filipin labelling to resemble the poorly labelled luminal membrane. These findings, although they cannot be interpreted definitely at present, clearly show impressive changes of membrane structure along the secretory pathway and suggest that a corresponding degree of functional specialization is needed for proper interaction to occur.

Animals↗
PubMed1981

[Ultrastructural visualization of binding and internalization of cholera and tetanuts toxins].

In monolayer cultures of a liver line, a population of non-coated membrane microinvaginations is preferentially involved in both the initial binding and subsequent internalization of colloidal gold-labelled cholera and tetanus toxins. These two toxins thus appear to be internalized via another pathway than most other polypeptide ligands studied, which enter cells via coated plasma membrane invaginations.

Animals↗
PubMed1981

[Heterocellular coupling in cultures of endocrine pancreatic cells].

The intracellular injection of 6-carboxyfluorescein in endocrine cells of cultured Rat pancreas followed by the characterization, by electron microscopy, of the injected cells shows that the dye is transferred from the injected cell into adjacent cells, presumably by gap junctions (nexus) = intercellular coupling. The transfer occurs not only between insulin-containing cells (B-cells), but also between B-cells and glucagon containing cells (A-cells) or somatostatin-containing cells (D-cells). The demonstration of homo- and heterocellular coupling in the endocrine pancreas supports the hypothesis that a direct exchange of molecules between islet cells may participate in the regulation of the secretory behavior of the islet of Langerhans.

Animals↗
PubMed1981

Vitamin D--dependent calcium binding protein: immunocytochemical localization in chick kidney.

A vitamin D--dependent calcium binding protein in the chick kidney that was detected by immunocytochemical techniques was localized exclusively in the distal convoluted tubule, the initial collecting tubule, and the early part of the collecting tubule. The intercalated (mitochondria-rich) cells in these tubular segments were negative for the calcium binding protein. Subcellularly, the protein was found in the cytosol and the nucleus of the tubular cells. The results suggest a role for vitamin D--dependent calcium binding protein in intracellular calcium metabolism rather than a direct involvement in membrane-mediated calcium reabsorption in the avian kidney.

Animals↗
PubMed1981

Polypeptide hormone degradation and receptor regulation are coupled to ligand internalization. A direct biochemical and morphologic demonstration.

Binding of a polypeptide hormone such as human growth hormone (hGH) to the cell surface initiates at least three diverse events: generation of a biologic signal, ligand degradation, and regulated receptor loss. Morphologic studies demonstrate that the ligand is internalized by the cell at physiologic temperature and associates intracellularly with lysosomes. Lysosomotropic agents such as NH4Cl and chloroquine inhibit the degradation of cell-associated 125I-hGH and promote irreversible binding of the ligand to the cell in a concentration, time, and temperature fashion. When 0.45 nM hGH is incubated with the cultured human lymphocyte at 37 degrees C, receptor loss occurs in parallel with the internalization of 125I-hGH under the exact same conditions of concentration, time, and temperature. NH4Cl is additive with submaximal concentrations of hGH in inducing receptor down regulation. These studies support the concept that ligand degradation and receptor loss are coupled to initial receptor binding by the internalization process.

Ammonium Chloride↗