Bromocriptine/SKF38393 ameliorates islet dysfunction in the diabetic (db/db) mouse

Dysfunction of pancreatic islets plays a crucial role in the etiology of type II diabetes. Chronic hyperglycaemia or hyperlipidaemia may impair islet function. Previous studies by our laboratory have demonstrated that dopaminergic agonists ameliorated hyperglycaemia and hyperlipidaemia in obese and diabetic rodents. In the present study, we investigated the effect of a treatment with the dopamine D₂ /D₁ receptor agonists (bromocriptine/SKF38393, BC/SKF) on islet dysfunction in db/db mice. Our results show that a 2-week BC/SKF treatment markedly reduced hyperglycaemia and hyperlipidaemia, and significantly improved islet dysfunction demonstrated by an increase of secretagogue-stimulated insulin release from islets of db/db mice to levels observed in islets from lean mice. There was also a fourfold increase of insulin content in the pancreas of BC/SKF-treated db/db mice compared with that in untreated controls. The effect of BC/SKF on islet function cannot be mimicked in pair-fed animals. BC/SKF had no direct stimulatory effect on islet insulin secretion, suggesting BC/SKF treatment improved islet function via an indirect mechanism. This treatment markedly improved the abnormally elevated daily levels of corticosterone, blood glucose and plasma lipids, supporting the view that BC/SKF may affect the neuroendocrine system that in turn regulates peripheral metabolism and thereby improves islet function. Received 3 April 1998; accepted 27 April 1998     

Expression of endogenous murine leukaemia viruses in AKR/J streaker mice

MICE of the AKR/J strain show high rates of spontaneous thymic lymphoma and are chronically infected with murine leukaemia viruses. Total thymectomy in young mice of this strain results in a marked decrease in the incidence of leukaemia. The finding of athymic mutant mice on the AKR/J background (referred to as streaker mice) is of importance in the study of genetic factors which influence virus expression and leukaemogenesis. Here we report that mice of both normal and mutant genotypes vary in the expression of a particular class of murine leukaemia virus. This lower virus expression in conjunction with the absence of a thymus leads to a lower tumour incidence in streaker mice.     

A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep

Texel sheep are renowned for their exceptional meatiness. To identify the genes underlying this economically important feature, we performed a whole-genome scan in a Romanov x Texel F2 population. We mapped a quantitative trait locus with a major effect on muscle mass to chromosome 2 and subsequently fine-mapped it to a chromosome interval encompassing the myostatin (GDF8) gene. We herein demonstrate that the GDF8 allele of Texel sheep is characterized by a G to A transition in the 3' UTR that creates a target site for mir1 and mir206, microRNAs (miRNAs) that are highly expressed in skeletal muscle. This causes translational inhibition of the myostatin gene and hence contributes to the muscular hypertrophy of Texel sheep. Analysis of SNP databases for humans and mice demonstrates that mutations creating or destroying putative miRNA target sites are abundant and might be important effectors of phenotypic variation.     

Zusammenhang zwischen Konzentration der 7-Methylbisdehydrodoisynolsäure im Uterus und ihrem Wachstumseffekt

Summary After administration of methylbisdehydrodoisynolic acid (1-ethyl-2-methyl-7-methoxy-tetrahydro-phenantryl-2-carbonic acid) the content of this oestrogen in the uterus of the spayed rat has been determined. It has been found, that a concentration of 3–4/100 g uterus tissue is necessary for the growth reaction of the organ. The concentration in the uterus lies between the concentration of muscle and liver. So the specific sensitivity of the uterus must be responsable for his reaction to an oestrogen.     

Protective action of irradiated bone marrow cells

Zusammenfassung Wurdein vitro röntgenbestrahltes Knochenmark (475r, 950 r, 1425 r) in letal bestrahlte Mäuse (LD 100/11=950 r) injiziert, so ergab sich: Isologes Knochenmark, mit 950 r bestrahlt, besitzt noch beachtliche Schutzwirkung; bestrahltes homologes und heterologes Knochenmark war weniger oder ganz inaktiv.     

Mutations in genes in the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis

Autosomal recessive renal tubular dysgenesis is a severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (Potter phenotype). Absence or paucity of differentiated proximal tubules is the histopathological hallmark of the disease and may be associated with skull ossification defects. We studied 11 individuals with renal tubular dysgenesis, belonging to nine families, and found that they had homozygous or compound heterozygous mutations in the genes encoding renin, angiotensinogen, angiotensin converting enzyme or angiotensin II receptor type 1. We propose that renal lesions and early anuria result from chronic low perfusion pressure of the fetal kidney, a consequence of renin-angiotensin system inactivity. This is the first identification to our knowledge of a renal mendelian disorder linked to genetic defects in the renin-angiotensin system, highlighting the crucial role of the renin-angiotensin system in human kidney development.     

Halbe haploide Chromosomenzahl im Hoden vonMyrmica sulcinodis Nyl. (Formicidae)

Summary In the testes ofMyrmica sulcinodis there are not only haploid and some diploid cells to be found, as in the testes ofM. ruginodis, M. sabulsti andM. rubida, but a large mass of cells that have only half the haploid chromosome number. The diploid chromosome number ofM. sulcinodis is 56, those of six otherMyrmica species are between 42 and 48.     

Über die Entwicklung des Fremdkörpergranuloms in verschiedenen Organsystemen

Summary The weight has been measured of the granuloma produced after implantation of the same foreign body in the kidneys, the testes, the liver and the subcutaneous tissue of male rats. It was found that granulomae in the testes and liver are nearly twice as heavy as in the kidney or in the subcutaneous tissue. Enhancement or inhibition of this reaction by treating the animals with cortexone shows organ-dependent effects on granuloma formation.