Post-receptor insulin resistance after diazoxide in non-insulin dependent diabetes

Insulin binding to monocytes and the counterregulatory hormone response to intravenous insulin was determined in six normal subjects and eight patients with non-insulin dependent diabetes mellitus (NIDDM), before and after seven days treatment with oral diazoxide. In the normal subjects diazoxide had no effect on insulin binding or sensitivity. In the patients with NIDDM diazoxide caused resistance to intravenous insulin with no change in the counterregulatory hormone response or in insulin binding to account for this. Diazoxide appears to cause post-receptor insulin resistance in NIDDM, and it may be a useful tool for studying post-receptor binding events.     

Intravenous injection of propylene glycol causes pulmonary hypertension in sheep

Propylene glycol (30%) is the carrier base for pentobarbital sodium in preparations often used in research laboratories. It has caused pulmonary hypertension in calves, and we found it caused pulmonary hypertension in sheep as well. To investigate the mechanism of pulmonary hypertension with propylene glycol, we injected an average loading dose of 30% propylene glycol (0.5 ml/kg) into adult sheep, which was followed by a rise in thromboxane levels (P less than 0.05) in systemic arterial plasma and lung lymph and by a dramatic increase in pulmonary arterial pressure (17 +/- 1 to 35 +/- 4 mmHg, P less than 0.05) and a fall in cardiac output (2.7 +/- 0.5 to 1 +/- 0.2 l/min). Indomethacin pretreatment blocked the rise in thromboxane in lung lymph and arterial plasma and substantially, although not entirely, blocked the rise in pulmonary arterial pressure. Pulmonary intravascular macrophages (PIMS), which are present in sheep and calves, can release thromboxane in response to a stimulus. To test whether PIMS might be the source of the thromboxane and pulmonary hypertension, we injected propylene glycol into guinea pigs and dogs, which are reported to have no PIMS, as well as into newborn lambs, which are not believed to develop many PIMS until the 2nd wk of life. In dogs and guinea pigs there was no response to propylene glycol. In lambs there was a rise in pulmonary vascular resistance but significantly less than in adult sheep; indomethacin blocked this response.(ABSTRACT TRUNCATED AT 250 WORDS)     

Voltage-activated currents in the CRI-G1 rat insulin-secreting cell-line.

1. The whole-cell configuration of the patch-clamp recording technique was used to characterize the electrophysiological properties of CRI-G1 insulin-secreting cells. 2. Current-clamp recordings demonstrated the excitable nature of these cells. 3. Voltage-clamp recordings revealed the presence of an inward Na+ current, an inward Ca2+ current and a delayed outward K+ conductance. 4. The electrophysiological properties of CRI-G1 closely resemble those of pancreatic beta-cells, thereby rendering this cell-line as a useful alternative to freshly isolated cells for the study of pancreatic beta-cell electrophysiology and pharmacology.     

Genetic structure of an aphid studied using microsatellites: cyclic parthenogenesis, differentiated lineages and host specialization

In a previous study, samples of the grain aphid Sitobion avenae (F.) were collected from wheat and adjacent cocksfoot hosts in a population thought to be primarily parthenogenetic, and DNA from individual aphids was analysed with a multilocus technique. Here we have applied single-locus microsatellites and a mitochondrial DNA marker to a subset of the same DNA extracts, and have made several additional inferences about important genetic and population processes in S. avenae . Microsatellite analysis indicated very high levels of genic and genotypic variation. S. avenae fell into three genotypic groups inferred to be almost noninterbreeding, while analysis of linkage and Hardy-Weinberg equilibria suggested high levels of sexual recombination within each genotypic group. Host specialization was evident: one lineage was found only on wheat, and one (bearing many alleles inferred to be introgressed from the blackberry-grass aphid S. fragariae (Walker)) was found only on cocksfoot. The third group of interrelated genotypes was found commonly on both hosts. Although most genotypes were found only once, some were much more numerous in the sample than expected from the frequency of the alleles they contained. This, and rapid temporal changes in genotypic composition of samples, indicates strong selective differences between genotypes and lineages. In the major genotypic group, the commonest genotypes were significantly more homozygous than were rare ones: thus these data may help to explain the frequent observation of homozygous excess in aphid allozymes. The genotype group showing S. avenae -like as well as S. fragariae -like alleles also carried S. fragariae -like mitochondrial DNA in at least 25/31 cases, indicating gender-asymmetrical hybridization.