Search Results - (Author, Cooperation:Hellerström)

1365-2133

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

The Cartesian diver microgasometer was used to study the oxygen consumption in microdissected samples of the basal parts of epidermis. Specimens were taken from guttate lesions and uninvolved skin of psoriatic patients and also from subjects without psoriasis. Incubations were performed in TC 199 phosphate medium supplemented with either 5·6 mM glucose, 20 mM pyruvate or oxalacetate and/or 10 mM sodium succinate. Without supplements to the medium the oxygen consumption averaged 16 mmol./hr. and kg. dry weight and no differences were found between the normal epidermis and the 2 types of psoriatic epidermis. Addition of glucose or pyruvate did not change the rate of respiration. In normal epidermis and in the unaffected epidermis from patients with psoriasis the oxygen uptake increased by a factor of 1·5 after addition of succinate. A much more intense stimulation was obtained by succinate in the guttate psoriatic lesion2 the oxygen consumption in these experiments increased by a factor of 6·8. Oxalacetate did not influence the respiration in the absence of succinate, but a strong inhibitory effect was evident in all epidermal groups studied after addition of succinate. The results indicate that in the psoriatic lesion the cells have a considerable capacity for metabolic energy production.

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1476-4687

Nature Archives 1869 - 2009

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

[Auszug] Biopsies were taken from the uncinate process, the body and the tail of the pancreas in 8 adult dogs of both sexes, anaesthetized with 'Nembutal^'. The pancreatic samples were fixed in Bouin's solution and, after dehydration and clearing, embedded in paraffin. Serial sections, 4pi thick, were ...

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1437-1596

Springer Online Journal Archives 1860-2000

Medicine

Law

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1420-9071

Springer Online Journal Archives 1860-2000

Biology

Medicine

Zusammenfassung Schwefelmikrobestimmungen wurden an isolierten Langerhansschen Inseln fettleibiger Mäuse ausgeführt. Die Schwefelkonzentration der Inseln war nahezu zweimal so hoch wie die des exokrinen Pankreasparenchyms. Nach Nahrungsentzug wurde in den Inseln keine signifikante Veränderung des Schwefelgehaltes festgestellt.

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1420-9071

Springer Online Journal Archives 1860-2000

Biology

Medicine

Zusammenfassung Nachweis, dass fettsüchtige, hyperglykämische Mäuse nach Alloxan-Injektion einen erhöhten Blutzuckerspiegel und herabgesetzte Insulinkonzentrationen im Vergleich mit den unbehandelten Kontrolltieren zeigen. B-Zellen der Langerhansschen Inseln zeigen nach Alloxan nekrotische Veränderungen.

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1432-1440

Springer Online Journal Archives 1860-2000

Medicine

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1432-1440

Springer Online Journal Archives 1860-2000

Medicine

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1432-1440

Springer Online Journal Archives 1860-2000

Medicine

Zusammenfassung Die Feststellungen vonhellerstrÖm undwassÉn Über die pathogéne Wirkung des Buboinhalts der Lymphogranulomatosis inguinalis auf das Affengehirn bei direkter Einimpfung ließen Parallelversuche mit Ulcus molle erwünscht erscheinen. Für solche Versuche dürfte sich der Inhalt von Ulcus molle-Bubonen weniger als die Ulcus molle-Reinkultur eignen. Ein mit einer frischen virulenten Ulcus molle-Reinkultur an 3 Affen (Cercopithecus callitrichus) durchgeführter Versuch hat eindeutig ergeben, daßdie Ulcus molle-Infektion für das Affengehirn nicht pathogen ist. Zur Herstellung und Fortzüchtung der Kultur hat sich am besten ein einfaches Gemisch von 1 Teil defibriniertem Menschenblut mit 4 Teilen physiol. Kochsalzlösung bewährt.

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1476-4687

Nature Archives 1869 - 2009

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

[Auszug] Male Sprague Dawley rats, weighing about 95 g and allowed free access to food and water, were separated into two groups: (1) Ten rats received subcutaneous injections of glucagon (Eli Lilly and Co.) dissolved in glycine sodium hydroxide-sodium chloride buffer (0.1 M, pH 9.6), each injection ...

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1432-0428

Pancreatic islets ; microcirculation ; glucose-stimulation ; islet blood flow ; rats

Springer Online Journal Archives 1860-2000

Medicine

Summary Blood flow to the pancreatic islets of the rat was estimated with the microsphere technique. Experiments with microspheres of different sizes (diameter 10, 15 or 50 μm) showed that optimal results were obtained with 10-μm spheres. Localization of microspheres either within or outside the islets was accomplished by freeze-thawing of the pancreas, making it transparent, so that both islets and microspheres could be distinguished in dark field illumination. Thus, microscopic examination of the freeze-thawed pancreas allowed the microspheres to be counted separately in both the endocrine and exocrine parenchyma. Under basal conditions, pancreatic blood flow was calculated as O.60 ml·min-1·g-1 (w/w). The islets accounted for about 10% of the total pancreatic blood flow, corresponding to 0.069 ml/min per whole pancreas. A bolus dose of glucose increased pancreatic blood flow to0.75 ml·min-1·g-1(p 〈0.05), while the fractional islet blood flow rose to 15.1% (p 〈0.001) corresponding to 0.125ml· min-1·pancreas-1 (p·〈0.001). The glucose-induced increase in pancreatic blood flow mainly resulted from increased flow to the pancreatic tail, while the corresponding increase in islet blood flow was uniformly distributed throughout the pancreas. Injection of the non-metabolizable glucose-derivate, 3-0-methyl-D-glucose, affected neither the pancreatic nor the islet blood flow. The data indicate that the islets receive more of the pancreatic blood flow than would be accounted for by their relative volume and that glucose preferentially stimulates blood flow to the islets.

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1432-0428

Insulin-dependent diabetes ; cellular immunity ; mouse ; streptozotocin ; auto-immunity

Springer Online Journal Archives 1860-2000

Medicine

Summary Anti-B cell auto-immunity may play a role in the pathogenesis of diabetes in mice resulting from multiple subdiabetogenic doses of the pancreatic B cell toxin, streptozotocin. In the present study we have investigated the cytotoxic anti-B cell response in these mice. A major role for B lymphocytes, macrophages, or their products in the cytotoxic response originally detected in vitro was eliminated by passing splenocytes from the mice treated with multiple subdiabetogenic doses of streptozotocin over a nylon wool column. The removal of the adherent cells enhanced the cytotoxicity against a rat insulinoma cell line in vitro by that expected due to enrichment of T-lymphocytes by approximately twofold. The induction of diabetes after multiple subdiabetogenic doses of streptozotocin is strain dependent. Mice of five strains were immunized with rat insulinoma cells, but only splenocytes from the two strains susceptible to multiple subdiabetogenic doses of streptozotocin demonstrated a significant cytotoxic response against the rat insulinoma cells in vitro. Mice pre-immunized with either the rat insulinoma cells or with syngeneic islets labelled in vitro with the hapten trinitrophenol developed hyperglycaemia more rapidly than control mice after multiple subdiabetogenic doses of streptozotocin. In the latter experiment the control mice immunized with complete Freund's adjuvant alone also became hyperglycaemic after a modified multiple subdiabetogenic dose of streptozotocin that did not cause diabetes in non-immunized mice. In mice pre-treated with either adjuvant or cyclophosphamide and then given a modified multiple subdiabetogenic dose of streptozotocin (35 mg/kg × 5 rather than 40 mg/ kg) the degree of hyperglycaemia was reduced and there was no protective effect of cyclophosphamide. However, the mice pre-treated with adjuvant again developed hyperglycaemia more rapidly and to a much higher level than did the mice given multiple subdiabetogenic doses of streptozotocin only. These additional data further support the hypothesis that B-cell destruction after multiple subdiabetogenic doses of streptozotocin results from triggering of an immune response against these insulin-producing cells.

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1432-0428

Springer Online Journal Archives 1860-2000

Medicine

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1432-0428

Springer Online Journal Archives 1860-2000

Medicine

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1432-0428

Islet amyloid polypeptide ; human pancreatic islets ; islet transplantation ; immune histochemistry ; hyperglycaemia

Springer Online Journal Archives 1860-2000

Medicine

Summary Human islets of Langerhans were transplanted to the subcapsular space of the kidneys of nude mice which were either normoglycaemic or made diabetic with alloxan. After 2 weeks, the transplants were processed for light and electron microscopical analyses. In all transplants, islet amyloid polypeptide (IAPP)-positive cells were found with highest frequency in normoglycaemic animals. IAPP-positive amyloid was seen in 16 out of 22 transplants (73%), either by polarisation microscopy after Congo red staining or by immune electron microscopy. At variance with previous findings of amyloid deposits exclusively in the extracellular space of islets of non-insulin-dependent diabetic patients, the grafted islets contained intracellular amyloid deposits as well. There was no clear difference in occurrence of amyloid between diabetic and non-diabetic animals. The present study indicates that human islets transplanted into nude mice very soon present IAPP-positive amyloid deposits. This technique may provide a valuable model for studies of the pathogenesis of islet amyloid and its impact on islet cell function.

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1432-0428

Sulphonylureas ; tolbutamide ; glibenclamide ; cartesian divers ; pancreatic islets ; metabolism of pancreatic B-cells ; respiration of isolated islets ; sulphonylurea effects on islets

Springer Online Journal Archives 1860-2000

Medicine

Résumé L'action des sulfonylurées hypoglycémiants sur la consommation d'oxygène des îlots pancréatiques isolés a été déterminée in vitro à l'aide d'un microrespiro-mètre cartésien. Les îlots provenaient du pancréas de souris obéses hyperglycémiques et contenaient plus de 90% de cellules B. L'addition de tolbutamide (D 860; 0.1 mg/ml) ou de glibenclamide (HB 419; 0.1 μtg/ml) au milieu d'incubation Krebs-Ringer-phosphate provoquait une augmentation de la consommation d'oxygène. La respiration augmentait avec la concentration de HB 419 entre 0.001 et 0.1 μg/ml, mais ne dépassait pas 120% de la respiration dans le milieu phosphaté pur. Tandis que le metabolite d'excrétion physiologique du D 860 n'influencait pas la respiration, le dérivé correspondant du HB 419 stimulait encore la captation d'oxygène des îlots. Quand les îlots étaient incubés avec une forte concentration de glucose (3 mg/ml) la captation d'oxygène était inhibée par l'addition de D 860, de son métabolite ou de HB 419. Cette dernière drogue augmentait légèrement la respiration des îlots incubés avec du glucose à la concentration de 1 mg/ml, tandis que l'on notait une stimulation très marquée pour une concentration de glucose encore plus faible (0.5 mg/ml). Les tentatives pour évaluer l'effet du mannoheptulose sur la réponse respiratoire des îlots aux sulfonylurées hypgloycémiants n'ont pas donné des résultats concluants. Il semble que les sulfonylurées produisent une augmentation de l'oxydation des substrats endogènes dans les cellules B des îlots pancréatiques.

Zusammenfassung Der Einfluß blutzuckersenkender Sulfonylharnstoffe auf den O2-Ver brauch isolierter Pankreas-Inseln wurde in vitro mit dem cartesianischen Taucher bestimmt. Die Inseln entstammten den Pankreas von Mäusen mit dem obese-hyperglycemic-Syndrom und bestanden zu über 90% aus B-Zellen. Zusätze von Tolbutamid (D 860, 0.1 mg/ml) oder Glibenclamid (HB 419, 0.1 μg/ml) zu den in Krebs-Ringer-Phosphat-Pufferlösung inkubierten Inseln führten zu Steigerungen des Sauerstoffverbrauchs. Für HB 419 wurde im Bereich von 0.001 bis 0.1 μg/ml ein konzentrationsabhängiger Effekt von maximal 120% der Kontroll werte nachgewiesen. Das Hauptausscheidungsprodukt von D 860 hatte auf die Respirationsrate keine Wirkung. Der Metabolit von HB 419 steigerte dagegen signifikant den Sauerstoffverbrauch. Wenn Inseln in Gegenwart hoher Glucose-konzentrationen (3 mg/ml) vorinkubiert wurden, dann wurde der Sauerstoffverbrauch durch Zusatz von D 860, seinem Metaboliten und auch von HB 419 gehemmt. Bei geringerer Glucosekonzentration von 0.5 und 1.0 mg/ml verursachte HB 419 jedoch eine Steigerung des Sauerstoffverbrauchs. Der Stimulationseffekt von HB 419 konnte einerseits durch nachfolgenden Zusatz von Mannoheptulose nicht unterdrückt werden, andererseits aber bei Vorinkubation der Inseln zusammen mit Mannoheptulose nicht mehr ausgelöst werden. Aus den Resultaten wird geschlossen, daß Sulfonylharnstoffe zu einer gesteigerten endogenen Substratoxydation in den B-Zellen der Langerhans'schen Inseln führen.

Summary Cartesian divers were used to evaluate the effects in vitro of some hypoglycaemic Sulphonylureas on the oxygen consumption of isolated pancreatic islets. The islet specimens were obtained from obese-hyper-glycaemic mice, and consisted of over 90% B-cells. When incubated with Krebs-Ringer phosphate medium, the islet cells displayed an increased rate of respiration upon addition to the incubation medium of either tolbutamide (D860; 0.1 mg/ml) or glibenclamide (HB 419; 0.1 μ.g/ ml). The respiratory rate increased with the concentration of HB 419 in the range 0.001–0.1 μg/ml, but did not exceed 120% of the respiration in pure phosphate medium. Whereas the physiological excretion product of D 860 did not affect the respiratory rate, the corresponding derivative of HB 419 was still effective in stimulating the oxygen uptake of the islets. When islets were incubated with glucose at a high concentration (3 mg/ml), the oxygen uptake was inhibited by addition of D 860, or its metabolite, or HB 419. The last drug slightly increased the respiration of islets incubated with glucose at a concentration of 1 mg/ml, and a marked stimulation was noted at a still lower glucose concentration, 0.5 mg/ml. Attempts to evaluate the effect of mannoheptulose on the respiratory response of the islets to hypoglycaemic Sulphonylureas produced inconclusive results. It is suggested that Sulphonylureas effect an increased rate of endogenous substrate oxidation in the B-cells of the pancreatic islets.

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1432-0428

Somatostatin ; diabetic Chinese hamsters ; islet cells ; A1-cells ; glucagon ; insulin ; hypothalamus ; stomach

Springer Online Journal Archives 1860-2000

Medicine

Summary The inhibitory effects of somatostatin on the release of insulin and glucagon, as well as its localization to the A1-cells (D-cells) of the pancreatic islets, suggest a role of this peptide in carbohydrate metabolism. In the present study we have measured the percentage islet volume, the total weight of the A1-cells and the somatostatin concentration in the pancreas of normal and spontaneously diabetic Chinese hamsters. In addition, the concentration of somatostatin in the stomach and hypothalamus as well as the insulin and glucagon content of the pancreas were evaluated. The percentage islet volume in the normal hamsters was 0.66±0.12, which was in marked excess of that in the diabetic group, 0.38±0.04. Similarly, the total weight of the A1-cells in the controls, 0.17±0.02 mg, was significantly larger than that in the diabetic animals, 0.12±0.02 mg. In agreement with these findings there was also a decreased pancreatic concentration of insulin and somatostatin, whereas the glucagon concentration was in the normal range. Also the stomach of the diabetic hamsters showed a decreased concentration of somatostatin. In the hypothalamus the total content of somatostatin appeared similar in the two groups of animals, but when expressed per mg wet weight this value was also decreased in the diabetic hamsters. These observations strongly suggest that, in the diabetic Chinese hamster, apart from the well-known B-cell deficiency there exists also a decreased functional activity of the somatostatin-producing cells.

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1432-0428

Islet β cell ; cyclosporin A mouse

Springer Online Journal Archives 1860-2000

Medicine

Summary In the light of recent attempts to treat newly-diagnosed Type 1 (insulin-dependent) diabetic patients with cyclosporin A, and reports suggesting an impaired glucose tolerance following immunosuppresion therapy with cyclosporin A, we investigated the long-term effects of cyclosporin A on islet β-cell morphology and function in vitro. Collagenase-isolated mouse pancreatic islets were cultured free-floating for 7 days in medium RPMI 1640 + 10% calf serum in the presence of cyclosporin A (0.1 or 1.0 mg/l). Islets cultured in the presence of the higher cyclosporin A concentration had impaired islet proinsulin biosynthesis and insulin release when challenged with high glucose concentration. Moreover, the insulin content of the drug-exposed islets was decreased and so was the rate of DNA synthesis. The glucose oxidation and respiratory rates, however, remained unaffected, suggesting that the impaired insulin production was not a result of defective oxidative metabolism. There were no changes in the ultrastructure or phospholipid biosynthesis of the islets after the drug treatment. These data indicate that cyclosporin A affects islets in culture, the clinical implications of which are so far difficult to assess. The inhibitory effect of cyclosporin A on islet cell DNA synthesis must nevertheless be considered in attempts to ameliorate Type 1 (insulin-dependent) diabetes, and when grafting islet cells in numbers primarily insufficient to cure the recipient.

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1432-0428

Pancreatic B cell ; pancreatic islet ; B-cell differentiation ; islet blood flow ; B-cell proliferation ; B-cell cycle ; hereditary diabetes

Springer Online Journal Archives 1860-2000

Medicine

Summary Most research on the pancreatic B cell has so far focussed on the regulation and molecular biology of insulin biosynthesis and release. The present review draws attention to some additional areas of islet research which have become accessible to investigation by recent methodological progress and which may advance our understanding of the role of the B cell in diabetes. There is now evidence to suggest that B cells arise from a pool of undifferentiated precursor cells in the fetal and newborn pancreas. These cells may contribute to islet growth and, if inappropriately stimulated, also to early islet hyperplasia. In the postnatal state, B-cell function is finely tuned by a complex set of incoming signals, one of which is the nutrient supply provided by the blood. Recent studies indicate that a disproportionately high fraction of pancreatic blood is diverted to the islets and that the islet blood flow is increased by glucose. An acute stimulus to insulin release may thus be accompanied by a process which enhances the distribution of the hormone to the target cells. Long-term adjustments of B-cell function are made by changes in B-cell number and total mass. Adaptive growth responses to an increased insulin demand occur in a number of hereditary diabetic syndromes in animals, but in some of these there is an inherited restriction on the capacity for B-cell proliferation leading to further deterioration of the glucose tolerance. Some evidence suggests that a similar mechanism may operate also in human non-insulin-dependent diabetes. A critical appraisal of this hypothesis requires, however, that human B cells should be tested for their growth characteristics. Studies of B-cell proliferation in experimental animals have shown that the B cell passes through the cell cycle at a relatively high rate but that the fraction of proliferating cells is low. Regulation of growth of the total B-cell mass seems to take place by changes in the number of B cells passing through the cell cycle rather than by changes in the rate of the cycle. The number of proliferating B cells also shows a marked decrease with age. It is at present uncertain to what extent these regulatory mechanisms apply also to the human B cell but it can be anticipated that further technical developments will elucidate this problem.

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1432-0428

Springer Online Journal Archives 1860-2000

Medicine

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1432-0428

Springer Online Journal Archives 1860-2000

Medicine

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