Glucose-stimulated oscillations in free cytosolic ATP concentration imaged in single islet beta-cells: evidence for a Ca2+-dependent mechanism

Normal glucose-stimulated insulin secretion is pulsatile, but the molecular mechanisms underlying this pulsatility are poorly understood. Oscillations in the intracellular free [ATP]/[ADP] ratio represent one possible mechanism because they would be expected to cause fluctuations in ATP-sensitive K(+) channel activity and hence oscillatory Ca(2+) influx. After imaging recombinant firefly luciferase, expressed via an adenoviral vector in single human or mouse islet beta-cells, we report here that cytosolic free ATP concentrations oscillate and that these oscillations are affected by glucose. In human beta-cells, oscillations were observed at both 3 and 15 mmol/l glucose, but the oscillations were of a longer wavelength at the higher glucose concentration (167 vs. 66 s). Mouse beta-cells displayed oscillations in both cytosolic free [Ca(2+)] and [ATP] only at elevated glucose concentrations, both with a period of 120 s. To explore the causal relationship between [Ca(2+)] and [ATP] oscillations, the regulation of each was further investigated in populations of MIN6 beta-cells. Incubation in Ca(2+)-free medium lowered cytosolic [Ca(2+)] but increased [ATP] in MIN6 cells at both 3 and 30 mmol/l glucose. Removal of external Ca(2+) increased [ATP], possibly by decreasing ATP consumption by endoplasmic reticulum Ca(2+)-ATPases. These results allow a model to be constructed of the beta-cell metabolic oscillator that drives nutrient-induced insulin secretion.     

Attachment relationships of adolescents who spent their infancy in residential group care: The Greek Metera study

A prospective longitudinal study beginning whilst the infants were living in the Metera Babies Centre showed that the great majority showed a disorganized attachment during the period of residential care, even though neither abuse/neglect nor subnutrition were involved. There was an initial follow-up post-adoption age at four years. This paper concerns a further follow-up of the 52 adopted adolescents aged 13 years who had spent their first two years of life in Metera Babies Centre. They were compared to 36 adolescents reared in their biological families who, during their infancy, attended full-time public day care. The key aim was to examine continuities and discontinuities between early and contemporary relationships. The Child Attachment Interview was employed in adolescence. The main findings were a significant decrease in the rate of disorganization and a lack of a significant difference between the previously institutionalized group and the family care comparison group on attachment qualities in adolescence. There was not sufficient statistical power, however, to detect a small difference.     

Low HbA1c and mortality: causation and confounding

This commentary provides an overview of the clinically important data linking low or lowered HbA_1c to increased total and CVD mortality in the general population, and in patients with diabetes. This sets the scene for a contribution in this issue of Diabetologia by Andersson et al (DOI: ) that suggests that BMI might modify the relationship between HbA_1c and mortality in patients with type 2 diabetes. The commentary provides a framework for the interpretation of epidemiological data from observational studies and clinical trials, and it addresses the clinical implications of this work. Finally, it highlights new research that is likely to advance this field.