Herwig Hahn von Dorsche

Age-dependent Insulin Secretion of the Endocrine Pancreas In Vitro from Fetuses of Diabetic and Nondiabetic Patients

Fetal hyperinsulinemia is assumed to play a key role in the pathogenesis of diabetic fetopathy. To investigate the role of enhanced fetal B-cell mass as one cause of fetal hyperinsulinemia during diabetic pregnancy, we studied human fetal pancreatic slices from diabetic women (FDW) with poor metabolic control and nondiabetic women (FNDW) between 11 and 26 wk of pregnancy, morphometrically and by in vitro incubation experiments. Abortions had been performed due to different medical indications. We found a good correlation between the calculated B-cell mass and the gestational age in both FDW and FNDW, but the increase in FDW was much more pronounced. Such a correlation was also found in vitro regarding the insulin response to glucose and IBMX. The FDW had significantly higher values than FNDW of the same age range. In contrast to this, we found in two diabetic patients with tight metabolic control during the whole pregnancy results similar to those in FNDW. Therefore, we assume that it could be possible to prevent fetal hyperinsulinemia and perhaps even diabetic fetopathy in diabetic women by tight metabolic control during the whole pregnancy, but further investigations are necessary.

Das Vorkommen biogener Amine in den Langerhansschen Inseln der Sandratte (Psammomys obesus)

Zusammenfassung Das Inselorgan von Sandratten (Psammomys obesus) wurde mit ultrahistochemischen Methoden auf das Vorkommen biogener Amine untersucht. Es konnte gefunden werden, das sowohl in A- als auch in B-Zellen Aminvesikel vom Typ der Catecholamingranula mit einem Durchmesser von 600 his 700 nm vorkommen. Daneben wurden 2 sehr selten auftretende Zelltypen angetroffen, die keinerlei typisehe Hormongranula enthielten, statt dessen aber in einem Falle ebenfalls Catecholamingranula, im anderen Falle Partikel, die nach ihrem elektronenoptischen Verhalten auf Serotonin-Granula schliesen lassen. Es wird festgestellt, das die Sandratte zu jenen Species gehort, die in A- und B-Zellen Amine enthalten konnen and die in ihrem Inselorgan 2 Amine nebeneinander besitzen. Die Bedeutung der Amine fur die Regelung der Hormonsekretion des Inselorgans wird erortert und auf die vermutbaren Beziebungen zum Diabetes mellitus hingewiesen.

Neuron-specific enolase (NSE) as a neuroendocrine cell marker in the human fetal pancreas

Using the PAP technique, we investigated the presence of neuron-specific enolase in the human fetal pancreas of 10, 12, and 14 weeks of gestational age. Neuron-specific enolase is present in the islet cells in the 10th week. Positive cells are situated mainly in duct epithelium. The number of cells with a positive reaction increases from the 12th to the 14th week. In the 14th week, they are clustered either near the ducts or between the acini. The numbers and localizations of the cells correspond to those obtained in previous studies with 4 basic islet cell types in the same material. The present results are a further proof that islet cells are biologically active during early fetal development.

Immunohistochemical investigations of β-endorphin in human pancreatic islets

The PAP technique was used to examine adult human pancreata (corpus) immunohistochemically for the presence of beta-endorphin containing cells. These cells were found to account for 4.8% of the islet cells. They are irregularly distributed within the islets, where they occur singly or in groups of 3 to 5 cells between the acini (0.4% of the parenchyma). Investigations designed to detect the simultaneous presence of beta-endorphin and somatostatin or glucagon revealed that beta-endorphin occurs in somatostatin cells (1.0% of the islet parenchyma). This is the 1st proof that these 2 hormones appear together. The simultaneous presence of beta-endorphin and glucagon in the same cell was also observed in 0.9% of the islet parenchyma. Earlier studies undertaken by us have shown that beta-endorphin is synthetized in the islets of Langerhans. Possible functions of beta-endorphin in the islets are discussed.

A-Zellenhyperplasie der Langerhansschen Inseln von Kaninchen nach Immunisierung mit Glukagon

Zusammenfassung Es sind histologische und immunhistochemische Untersuchungen der Langerhansschen Inseln von 9 Kaninchen nach deren Immunisierung mit Glukagon zwecks Gewinnung von Anti-Glukagonseren ausgefuhrt worden. Dabei konnte in den Inseln eine Hyperplasie der A-Zellen nachgewiesen werden, die mitunter so stark war, das diese Inseln vorwiegend aus A-Zellen bestanden.

Quantitativ-histologische Untersuchungen des fetalen menschlichen Pankreas von stoffwechselgesunden Frauen und insulinabhängigen Diabetikerinnen

Human fetal pancreases from nondiabetic (n = 26) and insulin-dependent diabetic women (n = 14) between the 13th and 26th week of pregnancy were investigated morphologically. There was in enhanced isle

Elektronenmikroskopische Untersuchungen an Langerhansschen Inseln von Sandratten (Psammomys obesus) vor Diabetesmanifestation

Zusammenfassung An „pr otodi abetischen“ Sandratten wurden elektronenmikroskopische Untersuchungen durchgefuhrt. In den Langerhansschen Inseln dieser Tiere findet man im Vergleich zur Kontrollgruppe eine Zusammenlagerung und Verschmelzung der β-Granula in den B-Zellen. In solchen B-Zellen ist uberdies eine Vermehrung der Mitochondrien, eine Vergroserung des G olgi -Apparates sowie eine Zunahme des rauhen endoplasmatischen Reticulums festzustellen. Folglich handelt es sich um stimulierte Zellen. Die A-Zellen zeigen eine leichte Degranulierung, und hin und wieder trifft man im Cytoplasma reichlich Lipofuscin-Granula an. Mithin sind auch diese Zellen stimuliert. Die D-Zellen erscheinen nach den elektronenmikroskopischen Befunden unverandert.

Histotopochemische und elektronenmikroskopische Untersuchungen am Pankreas von Wistar-Ratten mit Streptozotocin-Diabetes

Zusammenfassung Die Untersuchungen wurden an 15 streptozotocin-diabetischen Wistar-Ratten (Applikationeiner einmaligen Dosis von 64 mg/kg Korpergewicht Streptozotocin) und an einer Kontrollgruppe von 12 stoffwechselgesunden Wistar-Ratten durchgefuhrt. Die Mehrzahl der B-Zellen war weitgehend degranuliert, Insulin war mit histochemischenMethoden nur sparlich oder nicht nachzuweisen. Bei 11 der Versuchstiere waren an den A- und-B-Zellen pathologische Befunde zu erheben: Karyolysis, Auflosung der Zellmembranen und scholliger Zerfall des Cytoplasmas, mithin Kriterien der Nekrose. Auserdem wurde eine rundzellige Infiltration als Zeichen einer “Insulitis” gefunden. Im Elektronenmikroskop wiesen die B-Zellen nur vereinzelte Granula auf. Das endoplasmatischeReticulum war nur schwach entwickelt and zeigte kaum Ribosomenbesatz. Mitochondrien waren nur sparlich vorhanden, und der Golgi-Apparat fehlte ganzlich. Die Zellmembran war glatt und nicht durch Mikrovilli vergrosert. Emiocytose-Figuren fehlten. An den Nuclei waren keine Veranderungen erkennbar. Die Befunde an den Zellorganellen stimmen gut mit den lichtmikroskopischen Resultaten uberein. Im exokrinen Parenchym waren Bezirke vorhanden, die sowohl eine Auflosung der Lappchenstrukturals auch der einzelnen Acini boten. Die Acinuszellen befanden sich in Nekrose. Das Bindegewebe war deutlich vermehrt. Im Stroma wurden Areale mit einer rundzelligen Infiltration im Sinne einer Pankreatitis gefunden. Diese wie die aus der Literatur diskutierten Befunde zeigen, das Streptozotocin nicht nur anden B-Zellen der Langerhansschen Inseln angreift, sondern auch am exokrinen Pankreas und an anderen Organen Veranderungen hervorruft.

β-Endorphin-immunoreactive cells in the human fetal pancreas

This investigation has been carried out on 50 samples of fetal pancreata from the 10th to the 32nd week of gestation using the PAP technique. beta-Endorphin-reactive cells were morphometrically recorded by means of the point-counting method. beta-Endorphin reactivity occurred for the first time during the 15th week. During further development, beta-endorphin cells were found inside and outside the islets. From the 18th to 23rd week, these cells were primarily localized in the islet periphery. From the 24th week, they rearranged and occurred in irregular positions mixed with other islet cells. This rearrangement took place with a 4 week delay compared with the basic cell types of the islet organ. The extrainsular portion of these cells in the exocrine parenchyma varied between 0.3% in the 27th week and up to 10% in the 22nd week. Concerning the adult human pancreas, it has been suggested whether beta-endorphin cells may be a 6th basic cell type of the islet organ. Previous studies on the coexistence of somatostatin, glucagon and beta-endorphin in the same islet cell and the morphometric analysis would support this assumption. Biochemical examinations indicate that beta-endorphin is a modulator of insulin, glucagon, and somatostatin secretion in the islet organ. This is supported by the fact that beta-endorphin cells have extended cell bodies which is typical of cells with paracrine function.

Dietary effects on (pro)insulin biosynthesis and insulin-degrading activity in islets from sand rats.

Sand rats were fed either a vegetable (vegetable group) or a standard pellet diet. After 14-16 weeks, the normoglycemic subgroup selected (pellet group) from the animals that had been maintained on the standard diet showed a modest increase in body weight. Plasma immunoreactive insulin levels were not significantly increased, but glucose-stimulated insulin release was elevated from islets isolated from sand rats of the pellet group. Insulin biosynthesis was estimated in vitro by measuring [3H]leucine incorporation into (pro)insulin at 1.5 or 15 mmol/l glucose. The rate of (pro)insulin biosynthesis was elevated only at 15 mmol/l glucose in islets from those normoglycemic sand rats fed the pellet diet when compared with islets from the vegetable group. Specific insulin-degrading activity, as determined by measuring degradation of 125I-labeled insulin, was also increased for islets from the pellet group. The metabolic state of these sand rats is thus associated with normoglycemia in vivo, and increased stimulated rates of insulin biosynthesis and degradation in pancreatic islets in vitro.