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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 26 (1970), S. 295-295 
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Zusammenfassung Die Untersuchung an endokrin wirksamen Zellen der Bauchspeicheldrüse bei normalen und adipösen Mäusen ergibt eine relative Vergrösserung des Nukleolus der endokrinen Zellen bei den adipösen Tieren, was als morphologisches Zeichen gesteigerter Insulinproduktion angesehen wird.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: B-cell ; db-gene ; diabetic mice ; glucose ; p-nitrophenyl phosphatase ; pancreatic islets ; rubidium accumulation ; rubidium efflux
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Fluxes of 86Rb+ and hydrolysis of p-nitrophenyl phosphate were measured in collagenase-isolated islets of diabetic C57BL/KsJ-db/db-mice and normal controls (C57BL/KsJ-+/+). Both types of islets accumulated Rb+ avidly, as originally reported for hand-dissected islets of non-inbred ob/ ob-mice. KsJ-db/db-mouse islets showed enhanced accumulation of Rb+ and normal acitivity of K+-activated nitrophenyl phosphatase. D-glucose, 20 mmol/l, inhibited Rb+ efflux in normal islets but not in those from KsJ-db/db-mice. The glucose insensitivity of Rb+ efflux was observed in young animals, which exhibit glucose-induced insulin release, as well as in old animals, which do not secrete insulin in response to glucose. The anomalous regulation of Rb+ efflux already present in young animals may bear on the liability of KsJ-db/db-mouse B-cells to develop defective control of membrane potential, an abnormal metabolism of cyclic AMP, and a marked failure of insulin secretory capacity.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 9 (1973), S. 210-216 
    ISSN: 1432-0428
    Keywords: Glibenclamide ; insulin release ; pancreatic islets ; sulfonylurea ; tolbutamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The study was aimed at testing the hypothesis that sulfonylureas do not readily penetrate the pancreaticβ-cells but more probably stimulate insulin release by a direct action on theβ-cell plasma membrane. Uptake of radioactively labelled tolbutamide and glibenclamide by microdissected pancreatic islets of obesehyperglycemic mice was compared with the uptake of 3-O-methyl-D-glucose, to which theβ-cells are permeable. In contrast to tolbutamide, glibenclamide was taken up in amounts exceeding the 3-O-methyl-D-glucose space of islets incubated in the absence of serum albumin. Uptake of the sulfonylureas was easily reversible. It was depressed by serum albumin, whereas glucose, leucine or diazoxide had no effects. Antimycin A,p-chloromercuriphenylsulfonic acid and chlorpromazine, all of which increase the uptake of extracellular space markers, strongly stimulated the islet uptake of tolbutamide and glibenclamide but had no effect on the uptake of glibenclamide by subcellular particles of homogenized islets. The results suggest that sulfonylureas bind reversibly to islet tissue but are normally restricted to the outside of theβ-cells.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 7 (1971), S. 252-255 
    ISSN: 1432-0428
    Keywords: Alloxan ; alanine ; diabetes ; galactose ; glucose ; glucose carrier ; leucine ; mannoheptulose ; mannose ; pancreaticβ-cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé On a étudié chez la souris les effets modifiants de certains sucres et acides aminés sur l'action diabétogéne de l'alloxane. La gravité du diabète est définie grâce à la mesure du taux de glucose dans le sang 48 h après l'injection d'alloxane. Selon les rapports antérieurs, le D-glucose et le D-mannose, mais pas le D-galactose, protègent contre le diabète provoqué par l'alloxane. Le même effet n'a pas été observé avec le D-mannoheptulose, la L-alanine ou la L-leucine. L'action protectrice du glucose a été annulée par un traitement préalable au mannoheptulose. En conclusion, l'alloxane et le glucose ne sont pas en compétition pour le même site biochimique dans la membrane de la celluleβ. La protection contre la toxicité de l'alloxane peut résulter, cependant, d'un changement de conformation sur la membrane de la celluleβ provoqué par le glucose, le transport du glucose, ou le métabolisme du glucose.
    Abstract: Zusammenfassung Es wurde an Mäusen der modifizierende Effekt von einigen Zuckern und Aminosäuren auf die diabetogene Wirkung von Alloxan studiert. Die Schwere des Diabetes wurde an Hand von Blutzuckermessungen 48 Std. nach der Alloxaninjektion beurteilt. In Überinstimmung mit früheren Berichten schützen D-Glukose und D-Mannose, jedoch nicht D-Galaktose gegen den Alloxandiabetes. Kein Effekt wurde mit DMannoheptulose, L-Alanin und L-Leuzin festgestellt. Der Schutzeffekt von Glukose wurde durch vorherige Behandlung mit Mannoheptulose aufgehoben. Daraus wurde geschlossen, daß Alloxan und Glukose nicht an der gleichen Stelle der Membran der β-Zelle angreifen. Jedoch kann der Schutz gegen die Alloxantoxizität auf einer konformationellen Änderung der Membran derβ- Zelle, welche durch Glukose, den Glukosetransport oder den Glukosemetabolismus herbeigeführt wurde, beruhen.
    Notes: Summary The modifying effects of some sugars and amino acids on the diabetogenic action of alloxan were studied in mice. The severity of diabetes was assessed by measuring the blood glucose level 48 h after the alloxan injection. In accordance with earlier reports, D-glucose and D-mannose, but not D-galactose, protected against alloxan diabetes. No such effect was observed with D-mannoheptulose, L-alanine, or L-leucine. The protective action of glucose was abolished by prior treatment with mannoheptulose. It is concluded that alloxan and glucose do not compete for a common biochemical site in theβ- cell membrane. Protection against alloxan toxicity may, however, result from a conformational change in the β-cell membrane induced by glucose, glucose transport, or glucose metabolism.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 19 (1980), S. 45-49 
    ISSN: 1432-0428
    Keywords: β-cell ; db-gene ; diabetic mice ; glucose ; K+-electrodiffusion ; pancreatic islets ; rubidium efflux
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Islets from diabetic C57BL/KsJ db/db mice and normal C57BL/KsJ +/+ mice were loaded with 86Rb+ and micro-perifused with nonradioactive medium for 25 min. The appearance of 86Rb+ in the effluent could be described as the sum of two exponential functions with different proportionality constants. The rapid efflux component may have represented washout from the extracellular space, and had about the same proportionality constant in normal and diabetic mice. The slow efflux component probably reflected efflux across the islet cell plasma membranes. At 3 mmol/l D-glucose in the medium, the slow efflux was significantly retarded in diabetic as compared with normal mice. In normal mice, but not in diabetics, 20 mmol/l D-glucose inhibited the slow efflux component. It is concluded that the basal K+ permeability is decreased in KsJ db/db mouse islet cells, and that this abnormality may explain their persistant depolarization at low glucose concentrations.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Diabetes mellitus ; pancreatic B-cells ; serum cytotoxicity ; serum complement ; islet cell antibodies ; rubidium accumulation ; insulin release ; autoimmunity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Serum from normal blood-donors and juvenile diabetic patients inhibited Rb+ accumulation and stimulated release of 51Cr and insulin in suspensions of dispersed pancreatic islet cells prepared from ob/ob mouse islets, which are rich in B-cells. The effects indicate the presence of a B-cytotoxic factor in human serum. Serum from mouse and fetal calf also inhibited the islet cell accumulation of Rb+. Toxicity was not suppressed by treating serum with protein A-Sepharose and did not correlate with islet cell binding of fluorescent antibodies to human immunoglobulin. Whereas all sera inhibited Rb+ accumulation, 3 of 6 diabetic patient sera, but no blood-donor serum, made the cells fluoresce on exposure to the fluorescent antibodies. Supporting a dependence on complement, toxicity remained after dialysis, but was destroyed by treating serum with zymosan-A or heating at 56 ° for 30 min.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Erythrocyte ; erythropoiesis ; insulin ; erythrocyte deformability ; erythrocyte shape ; ob/ob-mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The circulating erythrocytes in hyperglycaemic and hyperinsulinaemic obese (ob/ob) mice are enlarged with a decreased erythrocyte filtrability and an abnormally low resistance to osmotic stress. These changes probably reflect aberrations of erythropoiesis, as evidenced by enhanced staining for iron in the bone marrow, reticulocytosis, and increased erythrocyte volume fraction. Mature erythrocytes, reticulocytes, and late-phase basophilic erythroblasts were found to have larger diameters than their counterparts in control mice while myelopoiesis appeared to be unaffected. The average erythrocyte also displayed an increased cell volume and a decreased haemoglobin concentration. It is suggested that the stimulation of the erythroid cell line in ob/ob-mice might be a consequence of the hereditary hyperinsulinaemia.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 37 (1994), S. S112 
    ISSN: 1432-0428
    Keywords: Acetylcholine ; caffeine ; cyclosporin A ; insulin secretion ; islets ; noradrenaline ; transplantation ; verapamil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To test whether the transplantation of pancreatic islets affects their basic functions, collagenaseisolated mouse islets were inserted under the left renal capsule of recipient animals. After various periods of time, grafts were removed from the kidney and examined for insulin content and secretory dynamics in a perifusion system. During syngeneic (C57BL/6, BALB/c) or subsyngeneic (NMRI) intrastrain transplantation, the graft insulin content fell drastically during the first week and stayed low for at least 6 weeks; first-phase secretion in general appeared suppressed. Immunosuppression by cyclosporin A had little effect on (sub)syngeneic grafts but markedly improved the performance of allotransplants. Daily injections of the calcium antagonist, verapamil, enhanced the insulin secretory responses of isolated grafts, whether (sub)syngeneic or allogeneic. In syngeneic and subsyngeneic grafts, the potentiating effect of acetylcholine on glucose-induced insulin release was markedly diminished, whereas that of caffeine was not. Transplanted islets also exhibited a subnormal responsiveness to the inhibiting action of noradrenaline. It is concluded that chronic denervation and transplantation of pancreatic islets may cause fundamental changes in the betacell responses to physiological regulators of insulin release.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 7 (1971), S. 256-265 
    ISSN: 1432-0428
    Keywords: α-aminoisobutyric acid ; diazoxide ; dibut-yryl cyclic 3′5′-AMP ; glucose ; insulin release ; islets of Langerhans ; mannoheptulose ; membrane transport ; 3-0-methyl glucose ; neutral amino acids ; obese-hyperglycemic mice ; pancreaticβ-cell ; sodium ; sucrose space ; urea space
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Le transport de l'acide α-aminoisobutyrique (AIB) a été étudié dans des îlots pancréatiques microdisséqués de souris obèses-hyperglycémiques. Ces îlots sont caractérisés par une proportion inhabituellement élevée de celluleβ insulino-sécrétrices. Les principales observations suivantes ont été faites: 1. Les cellules des îlots montraient une captation concentrante d'AIB, aboutissant à des rapports de distribution bien plus élevés que l'unité. La captation était diminuée par l'anoxie et par la suppression de sodium du milieu. 2. La L-alanine et la L-méthionine, mais non la L-leucine, réduisaient l'accumulation d'AIB dans les îlots qui avaient été préincubés en l'absence d'acide aminé exogène. Après charge préalable avec la L-alanine il y avait une captation accrue d'AIB. 3. Le D-glucose, le D-galactose, le diazoxide, le 3′,5′-AMP cyclique dibutyril et le D-mannoheptulose avaient des effets mineurs ou non significatifs sur la captation d'AIB. 4. La libération d'AIB des cellules insulaires était stimulée par l'AIB exogène ou par la L-alanine. Les auteurs concluent que les cellulesβ pancréatiques contiennent un mécanisme pour le transport des acides aminés neutres semblable au système A de beaucoup d'autres cellules. L'effet stimulant du glucose sur la biosynthèse de l'insuline ne semble pas être assuré par l'intermédiaire de ce système. Le co-transport d'acide aminé et de sodium ne suffit probablement pas à provoquer une décharge d'insuline à partir de cellulesβ mûres.
    Abstract: Zusammenfassung Der Transport von α-Aminoisobuttersäure (ABS) wurde in mikrosezierten Pankreasinseln von fettsüchtigen hyperglykämischen Mäusen untersucht. Diese Inseln sind durch eine ungewöhnlich hohe Menge von Insulin sezernierendenβ-Zellen charakterisiert. Es wurden folgende wesentliche Beobachtungen gemacht: 1. Die Inselzellen führten eine konzentrierende Aufnahme von ABS durch. Die Aufnahme wurde durch Anoxämie und durch Fehlen von Natrium im Milieu verringert. 2. L-Alanin und 1-Methionin, aber nicht 1-Leuzin verringerten die Speicherung von ABS in den Inseln, die ohne exogene Aminosäuren vorinkubiert worden waren. Nach einer vorherigen Anreicherung mit 1-Alanin wurde ABS verstärkt aufgenommen. 3. D-Glukose, D-Galaktose, Diazoxid, dibutyryl zyklisches 3,5-AMP und D-Manno-heptulose hatten einen geringeren Effekt auf die ABS-Aufnahme. 4. Der Efflux von ABS aus den Inselzellen wurde durch exogenes ABS oder 1-Alanin stimuliert. Es wurde daraus geschlossen, daß dieβ-Zellen des Pankreas einen Mechanismus für den Transport von neutralen Aminosäuren, ähnlich dem A-System mancher anderer Zellen enthalten. Der stimulierende Effekt von Glukose auf die Insulin-Biosynthese scheint nicht durch diesen vermittelt zu sein. Der Ko-Transport von Aminosäuren und Natrium ist wahrscheinlich nicht ausreichend, um Insulin aus der reifenβ-Zelle zu entladen.
    Notes: Summary Transport of α-aminoisobutyric acid (AIB) was studied in microdissected pancreatic islets of obesehyperglycaemic mice. These islets are characterized by an unusually high proportion of insulin-secretingβ-cells. The following main observations were made. 1. The islet cells exhibited a concentrative uptake of AIB, yielding distribution ratios much higher than unity. The uptake was depressed by anoxia and by the omission of sodium from the medium. 2. L-Alanine and L-methionine, but not L-leucine, reduced the accumulation of AIB in islets which had been preincubated in the absence of exogenous amino acid. After preloading with L-alanine there was an enhanced uptake of AIB. 3. D-Glucose, D-galactose, diazoxide, dibutyryl cyclic 3′,5′-AMP, and D-mannoheptulose had minor or insignificant effects on the uptake of AIB. 4. Efflux of AIB from the islet cells was stimulated by exogenous AIB or L-alanine. It is concluded that the pancreaticβ-cells contain a mechanism for transport of neutral amino acids similar to the A-system of many other cells. The stimulating effect of glucose on insulin biosynthesis does not seem to be mediated by this system. Co-transport of amino acid and sodium is probably not enough to elicit a discharge of insulin from matureβ-cells.
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