Untersuchungen zur Inselzell-Regeneration, Hyperplasie und zu intrainsul�ren zellul�ren Beziehungen wahrend eines Langzeit-Streptozotocin-Diabetes bei Ratten

Abstract

Studies on islet cell regeneration, hyperplasia and intrainsular cellular interrelations in long.lasting streptozotocin diabetes in ratsSummary. Diabetes was induced in rats with various single i.v. doses of streptozotocin. The rats were killed 4--10 months thereafter. Marked hyperglycaemia, ketonaemia and a rise of plasma free fatty acids resulted. The weight increase was markedly reduced. There was a clear reciprocal correlation between the injected dose of the diabetogenic agent and plasma IRI. The same was true for the B-cell counts. There was a marked B-cell hypertrophy, whereas we found only slight indication for B-cell regeneration. In one animal a functioning B-cell adenoma developed and almost all the parameters tested were normalized. In the diabetic animals the Ae-eells were predominant in the islets of Langerhans and their mean nuclear diameters were increased. In the duodenal nmeosa no increase in the number of glucagonoeytes was found.We interpret this activity of the glueagonoeytes as a consequence of permanent and long-lasting hyperglyeaemia. Investigations sur la regdndration et l'hyperplasie des cellules dans les ilots de Langerhans et sur les interrelations cellulaires intrainsulaires dans le diab~te de longue durde provoqud par la streptozotocine chez le ratRdsumd. Par des doses diffgrentes de Streptozotocine i.v. on provoque chez des rats un diab6te d'une durde de 4 ~ 10 tools. On note une hyperglyc6mie sdv~re, une ac6ton@mie et une augmentation moddr6e des acides gras. La prise de poids est diminude de fagon marqude. --I1 existe une nette eorrdlation rdeiproque entre la quantitd d'agent diab@tog~ne injeetd et l'insuline immunordactive plasmatique (IRI). On trouve le m@me rapport entre le nombre des cellules Bet Ia quantitd de Streptozotocine. On note unc eorrdlation direete entre le nombre des eellules Bet I'IRI. --L'hypertrophie des eellules B est importante alors qu'on ne trouve que pea de signes de r@gdndration des ilots et des eellules B. --Chez un des rats on note l'apparition d'un addnome ~ cellules B fonctionnant, provoquant une normalisation du m6tabolisme glueidique. --Chez les animaux diabdtiques, les cellules A 2 prgdominent et le diam~tre moyen des noyaux est augment6. On ne note pas d'augmentation signifieative des glueagonoeytes de la muqueuse duod6nale.Nous consid@rons que eette augmentation de l'aetivit@ des glucagonoeytes est fonction de l'hyperglyedmie perm~nente et de longue durge.

Streptozotocin-induced partial beta cell depletion in nude mice without hyperglycaemia induces pancreatic morphogenesis in transplanted embryonic stem cells

“…Early studies in the hyperglycaemic rodent indicated that following a high dose of STZ, some but not significant numbers of beta cells were recovered [7]. A lower dose of STZ, producing less severe hyperglycaemia, resulted in permanent beta cell damage with negligible replacement of beta cells from the duct [8,9]. However, it is not clear from these studies whether the lack of beta cell recovery in STZ-treated animals with normal blood glucose levels resulted from an absence of regenerating factors or from an inability of potential endogenous beta cell progenitors to respond to nascent regenerating stimuli.…”

Evaluation and Optimization of Effective-dose of Alloxan for Inducing Type-2 Diabetes Mellitus in Long Evans Rat

“…22 Although streptozotocin is one of the most commonly used for induction of diabetes but it reported to have some disadvantages such as irreversible damage of the pancreatic β-cells, alloxan-induced diabetic model is preferable in recent years due to less toxicity and reversible damage of pancreas. 2,3,4 For inducing diabetes in experimental animals, use of a low dose of alloxan 23,24 has been reported earlier. A slide overdosing is highly toxic and may cause the loss of experimental animals.…”

“…Although streptozotocin (STZ) is most commonly used chemical agents for induction of diabetes in rats 1 , there are severe disadvantages also reported by several groups. 2,3 The most important disadvantage of using STZ has been reported that the spontaneous recovery from high blood glucose levels by the development of functioning insulinoma. 2,3,4 Higher incidence of kidney and liver tumours are also reported.…”

“…2,3 The most important disadvantage of using STZ has been reported that the spontaneous recovery from high blood glucose levels by the development of functioning insulinoma. 2,3,4 Higher incidence of kidney and liver tumours are also reported. 4 Therefore, alloxan (2,4,5,6-pyrimidinetetrone) which is the second most commonly used chemical for induction of diabetes mellitus 5 because of its low cost and easy availability.…”

Immunocytochemical changes in the fetal pancreatic islet following fetal administration of streptozotocin in the rat

“…It is generally accepted that B cells are poor regenerators (Lazarow, 1952) and that STZ-induced diabetes is to a large extent irreversible (Steiner et al, 1970). STZ causes DNA alkylation (Ledoux et al, 1986) and excision (Ueda and Hayashi, 1985); therefore, the activity of poly(ADP-ribose) synthetase in the islets is increased during the early phase of DNA repair (Uchigata et al, 1982).…”