Influence of postnatal overnutrition and pregnancy on non-insulin dependent diabetes induced in Wistar rats by neonatal streptozotocin.

Wistar rats with non-insulin dependent diabetes induced by neonatal streptozotocin (STZ) administration were raised either in large or in small litters. The STZ-treated rats from small litters showed a higher body weight as well as increased blood glucose levels compared with vehicle- and STZ-treated rats reared in large nests at an age of 8 weeks. The higher body weight of these rats was maintained until an age of 15 weeks, whereas the basal blood glucose was normalized. However, both STZ-treated groups exhibited an impaired glucose tolerance. During pregnancy only the glucose tolerance of the STZ-treated animals from large nests was improved although not normalized. The STZ-treated rats from small nests failed to adapt to pregnancy because the blood glucose levels after glucose load were similar to values found in the virgin state. The body weight of pregnant STZ treated rats raised in small litters was significantly lower than in vehicle- or STZ-terated rats from large nests. The number of fetuses per litter was similar in all groups tested. Compared with the vehicle-treated rats from large litters the fetal body weight of STZ-treated rats from small nests was decreased and that of STZ rats raised in large litters was increased. These results suggest that the rats with the more impaired glucose tolerance produce growth-retarded pups and, conversely, rats with rather mild impairment have bigger fetuses than the vehicle-treated ones. In the present study we have examined for the first time the combined effects of postnatal overnutrition and pregnancy on glucose homeostasis of rats treated neonatally with STZ. Our data demonstrate that postnatal overnutrition is an aggravating factor in the development of a diabetic state in these rats, especially at times when the insulin requirement is higher such as puberty and pregnancy.

[Clearance rate of gingiva and content of collagen of inflammated and clinically non-inflammated papilla interdentalis]. / Clearancerate der Gingiva und Kollagengehalt der entzündeten und klinisch entzündungsfreien Papilla interdentalis.

UNLABELLED: The gingiva vessel function has been defined by gingivitis (A), clinical sound gingiva without (B) and with loss in attachment (C) as well as the collagen fraction by biopsy material. The division of the probands at the age between 20 and 24 years into groups has been carried out after checking the SBI, PII (Silness/Loe) and the loss of attachment of the teeth 43-33. The vessel function has been found out through the impulse rate of the gingiva Xenon-133-clearance by calculating the clearance rates (CR) (groups: A1 n = 15; B1 n = 18; C1 n = 16). The vestibular interdental papillae have been elaborated in a second study for finding out the collagen fractions with the Stegemann method modified by Woessner (groups: A2 n = 18; B2 n = 10; C2 n = 12). The statistical reliability has been checked by the t-test (F-test) and the u-test by Mann and Whitney. RESULTS: In the clearance study the CR in group A1 are higher and in group C1 lower than in group B1. In the second study the increased collagen solubility in group A2 by inflammation is confirmed, in group C2 a significant higher share in unsoluble collagen and total collagen has been defined than in group B2.

Effect of gliadin on the distribution of sucrase among different fractions of fetal chick intestine.

The effect of peptic-tryptic digested gliadin (PT-gliadin) on the increase in sucrase activity in different fractions of tissue cultured fetal chick duodenum was investigated and compared with that of monensin, a known perturbant of the Golgi complex. PT-gliadin diminished the rise in sucrase activity in the tissue homogenate, in a brush border fraction, and in the high speed supernatant, whereas the activity in a Ca2+-pelleted fraction including endoplasmic reticulum and Golgi apparatus was unaffected. In contrast, monensin caused a proportional inhibition of the increase in sucrase activity in all fractions examined. The findings might suggest that PT-gliadin is able to affect intracellular processing of sucrase with the site of attack being distal to that of monensin in the biogenesis of the enzyme. Whether the effect of PT-gliadin on fetal gut is relevant also for celiac intestine remains to be established.

Behaviour of several enzymes of fetal chick intestine in tissue culture.

The behaviour of several enzymes is described of the fetal chick duodenum in tissue culture in a defined medium free of serum and hormones. During culture the activity of sucrase, maltase, alanine aminopeptidase, and gamma-glutamyltransferase is raised in tissue explants, whereas the activity of other enzymes (dipeptidyl peptidase IV, leucine amino-peptidase, alkaline phosphatase) remains constant. After culture, depending on the enzyme, a varying amount of activity is found in the medium, a part of which can be sedimented by ultracentrifugation. Sucrase is subject to the strongest increase in activity during culture and thus should represent a sensitive marker for investigating maturation processes in the fetal intestine and their disturbances.

Chicken fetal intestine in tissue culture.

A simple and reproducible method for cultivation of fetal chicken small intestine is presented. The culture was performed in a defined medium without serum. Duodena were excised from embryos at the 14th day of fetal development and cut in small segments that were maintained in culture until day 16. It could be shown that the morphology of cultured intestine resembles that of noncultured gut of corresponding age as judged by light microscopy. The increase in activity of sucrase and maltase in cultured explants is comparable with that of intestine in ovo, whereas that of alkaline phosphatase is lower than under in vivo conditions. Hormones (thyroxine, dexamethasone) influence the enzymic pattern of fetal intestine in a known manner. Therefore, the method permits maintenance of fetal intestine in tissue culture for 2 days, a period sufficient for investigation of maturation processes of intestinal mucosa.

Influence of gliadin on fetal chick intestine in tissue culture.

The purpose of this study was to develop a model system for detecting biological effects of gliadin which may be related to coeliac disease. The technique applied was tissue culture of chicken duodenum at several stages of fetal development. A normally occurring increase in disaccharidase activities in cultured tissue explants was diminished by the presence of peptic-tryptic digested gliadin or of a tryptic fragment of alpha-gliadin (alpha-GT 18,000). The effect of peptic-tryptic digested gliadin was only demonstrable in the early phase of fetal development (days 10-14), and disappeared at day 16. The release of enzymes into the culture medium was decreased by gliadin at the 12th day of fetal development. The results suggest that gliadin inhibits the differentiation processes of the fetal intestine.

[Comparative studies of the preparation of alpha-gliadin]. / Vergleichende Untersuchungen zur präparativen Darstellung von alpha-Gliadin.

alpha-gliadin was prepared from wheat flour by two different methods. The products were compared electrophoretically and by double radial immuno-diffusion. The alpha-gliadin fraction proved to be identical in the immunological test. Only the alpha-gliadin preparation received by ion exchange chromatography is suitable for further purification by multiple gel filtrations.

[Relationship between Na+ and monosaccharide influx across the microvilli membrane depending on the energy state of the intestinal mucosa wall]. / Relation zwischen Na+- und Monosaccharid-Influx über die Mikrovillimembran in Abhängigkeit vom Energiezustand der intestinalen Mukosazelle.

1. An energy dependence of the Na+ influx and of the "extra-Na+ influx" across the microvilli membrane was demonstrated in an in vitro preparation of the rat jejunum by adjustment of low ATP/ADP quotients. The monosaccharide influx does not show this dependence. 2. The similar relationship of monosaccharide-dependent Na+ influx and Na+ influx without monosaccharide with the energy state in the mucosa cells suggests a common control system. 3. A constant stoichiometry between monosaccharide and "extra-Na+ influx" can be maintained only under constant intracellular conditions. 4. The changes of the Na+ and K+ influxes by so-called Na+ dependently transported monosaccharides correspond to those which can be elicited by lowering the ATP/ADP ratio in the in vitro preparation. 5. A mechanism is discussed in which an ATP-utilizing reaction is stimulated in the microvilli owing to the monosaccharide transport, thus locally discontinuing the condition for uncoupling of an (Na, K)-ATPase and eliciting an "extra-Na+ influx".

[Effects of insulin, glucagon and secretin on intestinal resorption of glucose]. / Der Einfluss von Insulin, Glucagon und Sekretin auf die intestinale Glucoseresorption.

The authors describe a versatile experimental procedure for the study of intestinal digestion and resorption in animals. This procedure is based on the principle of the continuous perfusion of a completely isolated intestinal segment. The results from experiments on glucose absorption from the jejunum of the rabbit serve to demonstrate the great reproducibility of this in vitro technique. No hormonal influence on monosaccharide resorption could be detected by means of this procedure, even in case of unphysiologic dosage of insulin, glucagon and secretin.

[Quantitative relationship between the monosaccharide induced change in ion transport and the monosaccharide accumulation in the rat jejunum]. / Quantitative Beziehungen zwischen der monosaccharidbedingten Anderung des Ionentransports und der Monosaccharidakkumulation im Jejunum der Ratte

1. In the rat's jejunum, the changes induced by Na+-dependently transported monosaccharides (10 mM) of the unidirectional Na+- and K+-influx across the microvilli membrane were studied under varying metabolic conditions. 2. The monosaccharide induced change of Na+- and K+-influx is a function of the ion gradients active across the microvilli membrane. 3. In the in vitro preparation during the process of energy-dependent accumulation the monosaccharide induced change of permeability in the microvilli membrane decreases the K+ concentration, while the Na+ concentration increases. 4. The monosaccharide concentration in the tissue reaches a final value which is proportional to the change of Na+- and K+-influx and to the change in ion concentrations, and which is retained even upon compensation of the gradient and at low intracellular K+ concentrations. 5. The correlation between the breakdown of the ion gradient and the rise of monosaccharide accumulation is explained by the monosaccharide induced restriction of the active ion transport and the ensuing change of energy dissipation in favour of the monosaccharide transport. The (Na+ + K+)-ATPase in the microvilli membrane is discussed as being transmitter of the energy from the ion gradients.

Subcellular localization of (Na+ + K+)-activated ATPase in the brush border membrane of the mucosal cell of the rat small intestine.

The localization of (Na+ + K+)-activated ATPase was investigated in isolated brush borders of rat small intestinal mucosa. The purity of the fractions has been checked by morphological and enzymatic criteria. The brush borders were found to contain a significant quantity of (Na+ + K+)-activated ATPase. Separation of isolated brush borders into their substructures suggests that (Na+ + K+)-activated ATPase is localized deeper within the brush border region than invertase. These findings are discussed in relation to active monosaccharide transport in the intestine.