Decreased number of asialoglycoprotein receptors in diabetic BB Wistar rat

Summary The binding of asialoglycoproteins by hepatic binding protein was studied in freshly isolated hepatocytes from genetically diabetic BB Wistar rats. The number of cell surface asialoglycoprotein receptors was dramatically decreased (58,000±38,000 for diabetic rats compared to 267,000±70,000 for normal rats), while the association equilibrium constant was not changed. These results parallel those obtained with streptozotocin-diabetic rats and support the hypothesis that insulin deprivation is responsible for the decrease in the receptor number.     

Effect of monensin and diabetes on asialoglycoprotein degradation in rat hepatocytes

We have studied the effects of two modulations — streptozotocin-induced diabetes in vivo, and the presence of the carboxylic proton ionophore monensin in vitro — on the degradation of³H-asialoorosomucoid ligand in isolated rat hepatocytes.The ligand was internalized by means of a synchronous wave procedure. Diabetes was associated with a marked decrease in the amount of total degraded radioactive ligand compared to that in normal cells (3.6% and 37.3% of internalized ligand respectively, at 60 min), together with increased secretion of degradation products into the incubation medium (87% and 46.3% of the total degraded ligand was secreted by diabetic and normal cells, respectively). Monensin induced similar effects in normal cells, but had no apparent effect in diabetic cells.     

Effect of monensin and diabetes on asialoglycoprotein degradation in rat hepatocytes.

We have studied the effects of two modulations--streptozotocin-induced diabetes in vivo, and the presence of the carboxylic proton ionophore monensin in vitro--on the degradation of 3H-asialoorosomucoid ligand in isolated rat hepatocytes. The ligand was internalized by means of a synchronous wave procedure. Diabetes was associated with a marked decrease in the amount of total degraded radioactive ligand compared to that in normal cells (3.6% and 37.3% of internalized ligand respectively, at 60 min), together with increased secretion of degradation products into the incubation medium (87% and 46.3% of the total degraded ligand was secreted by diabetic and normal cells, respectively). Monensin induced similar effects in normal cells, but had no apparent effect in diabetic cells.     

The plasma volume of the Wistar rat in relation to the body weight

Summary The plasma volume of 43 male Wistar rats, weighing between 140 and 350 g, was determined. A close linear relationship between plasma volume and body weight was found: plasma volume (ml)=0.0291×body weight (g)+2.54.Acknowledgment. The excellent assistance of Mr J.S. Bouwer in animal experiments is gratefully acknowledged.     

Decreased cyclic GMP levels in rat cecum mucosa during adaptive stimulation of Na-K-ATPase.

In rat cecal mucosa, Na-K-ATPase specific activity and sodium and fluid absorption were increased by giving polyethylene glycol administration with the drinking water. Whereas cyclic AMP levels were unchanged, cyclic GMP was reduced by about 50%. This finding suggests a regulatory role of cyclic GMP in intestinal sodium and fluid absorption.     

Regulation of mitochondrial aconitase by phosphorylation in diabetic rat heart

Mitochondrial dysfunction and protein kinase C (PKC) activation are consistently found in diabetic cardiomyopathy but their relationship remains unclear. This study identified mitochondrial aconitase as a downstream target of PKC activation using immunoblotting and mass spectrometry, and then characterized phosphorylation-induced changes in its activity in hearts from type 1 diabetic rats. PKCβ₂ co-immunoprecipitated with phosphorylated aconitase from mitochondria isolated from diabetic hearts. Augmented phosphorylation of mitochondrial aconitase in diabetic hearts was found to be associated with an increase in its reverse activity (isocitrate to aconitate), while the rate of the forward activity was unchanged. Similar results were obtained on phosphorylation of mitochondrial aconitase by PKCβ₂ in vitro. These results demonstrate the regulation of mitochondrial aconitase activity by PKC-dependent phosphorylation. This may influence the activity of the tricarboxylic acid cycle, and contribute to impaired mitochondrial function and energy metabolism in diabetic hearts. Received 31 October 2008; received after revision 17 December 2008; accepted 2 January 2009     

Evaluation of monoaminergic receptors in the genetically epilepsy prone rat

Summary The intensity of sound-induced convulsions in the genetically epilepsy-prone rat (GEPR) was reduced in a dose related fashion by intracerebroventricular administration of dobutamine, (₁ agonist), terbutaline (₂ agonist) or phenylephrine (₁ agonist). BHT-920 (₂ agonist) did not cause a dose-related decrease in sound-induced convulsion intensity. Binding studies showed that whole brain and receptor densities (B_max) were normal while the K_d was increased for the ligand in GEPR brain.Acknowledgment. We are most grateful to Boehringer Ingelheim for generously supplying BHT 920. We are also indebted to Ciba-Geigy Corporation for the gift of terbutaline hydrochloride and phentolamine hydrochloride. The work was supported in part by NIH grant NS 16829.     

Evaluation of monoaminergic receptors in the genetically epilepsy prone rat

The intensity of sound-induced convulsions in the genetically epilepsy-prone rat (GEPR) was reduced in a dose related fashion by intracerebroventricular administration of dobutamine, (beta 1 agonist), terbutaline (beta 2 agonist) or phenylephrine (alpha 1 agonist). BHT-920 (alpha 2 agonist) did not cause a dose-related decrease in sound-induced convulsion intensity. Binding studies showed that whole brain alpha and beta receptor densities (Bmax) were normal while the Kd was increased for the beta ligand in GEPR brain.     

Decreased cyclic GMP levels in rat cecum mucosa during adaptive stimulation of Na−K-ATPase

Summary In rat cecal mucosa, Na–K-ATPase specific activity and sodium and fluid absorption were increased by giving polyethylene glycol administration with the drinking water. Whereas cyclic AMP levels were unchanged, cyclic GMP was reduced by about 50%. This finding suggests a regulatory role of cyclic GMP in intestinal sodium and fluid absorption.Acknowledgments. We thank Miss U. Kautz for engaged technical assistance, Dr G. Schultz, Pharmakologisches Institut der Universität Heidelberg, for valuable discussions and suggestions, and Dr. K.D. Schultz, Heidelberg, for generous supply of the cGMP antibody and 125-iodinated succinyl tyrosyl methyl ester of cGMP.Supported by the Deutsche Forschungsgemeinschaft, grant Lo 114/7.     

Early-life undernutrition causes deficits in rat dentate gyrus granule cell number

Recently developed stereological methods have been used in experiments to examine the effects of two levels of undernutrition during early postnatal life on the total number of rat dentate gyrus granule cells. This study has shown that previously undernourished rats have significant deficits in the total number of this particular type of neuron.     

Normal osteoclast number and function in rat pups lacking parathyroid hormone

Summary In parathyroidectomized suckling rats, bone modeling and the number and activity of cells in the osteoclast population are normal. These findings are at variance with observations in older animals and suggest that factors other than parathyroid hormone influence osteoclast formation and function in the neonate.This work was supported by grants HD-07419 and DE-04629 from the NIH. We thank Darrell Iler for his excellent technical assistance.     

Streptozotocin induced diabetic nephropathy and renal tumors in the rat

Summary Adult Wistar rats rendered diabetic by a single dose of streptozotocin develop renal morphological changes which show subtle differences compared to those seen in human diabetic renal disease. The early tubular degeneration is sited in the distal rather than the proximal convoluted tubule and subsequent glomerular lesion shows linear deposits of IgG and albumin in the basement membrane rather than in the mesangium. The carcinogenicity of streptozotocin in the rat is reconfirmed.Acknowledgements. We wish to thank Mr S.G. Watkins and Mrs D. Greening for technical assistance.     

X-ray induced increase in number of cysteine-rich periventricular glial cells in the rat brain

Zusammenfassung Nach einmaliger Röntgen-Kopfbestrahlung bei Ratten mit 3000 und 4000 R wurde eine statistisch gesicherte Zunahme der Zahl cysteinreicher periventrikulärer Gliazellen im Gehirn festgestellt.