Histogenesis of the endocrine pancreas in newborn rats after destruction by streptozotocin. An immunocytochemical study

Endocrine pancreatic tissue in newborn rats was studied 1 to 17 days after the destruction of B cells by an injection of streptozotocin. Regeneration of insulin cells was observed four days after streptozotocin injection, which was followed by recovery from the diabetic state and an increased pancreatic insulin content. Regeneration was characterised by new islets budding from small ducts. The pancreas of newborn rats, like the embryonic pancreas, thus retains a capacity to form endocrine tissue, although some degree of reduplication of preexisting B cells may also be involved in the process. Newborn rats injected with streptozotocin constitute an interesting model for the study of factors which may act on the regenerative potential of pancreatic endocrine tissue in the diabetic state.     

Postmaturity in the rat: phosphorylase, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities in the fetal liver.

Liver glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities were increased in the postmature rat fetus (23.5 day old) when compared to term rat fetus (21.5 day old). Postmaturity was without effect on liver phosphorylase activity. The three liver enzyme activities were also determined in normal 2 day old neonates. These results are correlated with the mobilisation of fetal liver glycogen occuring during postmaturity in the rat and are discussed in relation to the secretory pattern of the pancreatic hormones.     

Transmitted beta-cell dysfunction as a cause for type 2-diabetes

The pathways that control insulin release and regulate pancreatic beta-cell mass are crucial on the development of type 2 diabetes mellitus. Maturity-onset diabetes of the young comprises a number of single-gene disorders affecting beta-cell development and/or function. A genetic basis for the more common forms of type 2 diabetes which affect adults in developed as well as many developing countries is less clear cut. It is also characterized by abnormal beta-cell function. Appropriate inbred rodent models are an essential tool for the identification of genes and environmental factors that increase the risk of type 2 diabetes. The informations available from studies in the Goto-Kakizaki (GK) rat are here reviewed in such a perspective. This model was obtained by selective breeding of individuals with mild glucose intolerance from a non-diabetic Wistar rat colony. Heritability of defective beta-mass and beta-cell function in GK model is proposed to reflect the complex interactions of three pathogenic players: (1) three independent loci containing genes causating impaired insulin secretion; (2) gestational metabolic (hyperglycaemic) impairment inducing a programming of endocrine pancreas (decreased beta-cell mass) which is transmitted to the next generation; (3) secondary (acquired) loss of beta-cell differentiation due to chronic exposure to hyperglycaemia (glucotoxicity). A better understanding of the mechanisms involved in the failure of beta-cell function in the GK model will lead to identification of new therapeutic targets for both the prevention and treatment of type 2 diabetes.     

Ultrastructural study of pancreatic B cell regeneration in newborn rats after destruction by streptozotocin

An ultrastructural study of endocrine cells was performed in the pancreas of rats treated with a single dose of streptozotocin on the day of birth. Most of the B cells present at birth were destroyed by streptozotocin but some survived and could again synthesize insulin after eliminating their altered fragments in phago-lysosome structures. New B cells were produced primarily by the formation of new islets from the small pancreatic ducts. A study of mitosis in colchicine treated animals showed that most B cells present on day 4 were formed by mitosis of undifferentiated cells. No significant division of preexisting differentiated B cells could be shown in streptozotocin treated rats. B cell regeneration in this newborn rat model is thus explained primarily by budding of new islets from the ducts.