Diabetologia

, Volume 45, Issue 8, pp 1154–1163

Disorganization of cytoplasmic Ca2+ oscillations and pulsatile insulin secretion in islets from ob/ob mice

  •  M. Ravier
  •  J. Sehlin
  •  J. Henquin
Article

Heading

Abstract

Aims/hypothesis. In normal mouse islets, glucose induces synchronous cytoplasmic [Ca2+]i oscillations in beta cells and pulses of insulin secretion. We investigated whether this fine regulation of islet function is preserved in hyperglycaemic and hyperinsulinaemic ob/ob mice.

Methods. Intact islets from ob/ob mice and their lean littermates were used after overnight culture for measurement of [Ca2+]i and insulin secretion.

Results. We observed three types of [Ca2+]i responses during stimulation by 9 to 12 mmol/l of glucose: sustained increase, rapid oscillations and slow (or mixed) oscillations. They occurred in 8, 18 and 74% of lean islets and 9, 0 and 91% of ob/ob islets, respectively. Subtle desynchronisation of [Ca2+]i oscillations between regions occurred in 11% of lean islets. In ob/ob islets, desynchronisation was frequent (66–82% depending on conditions) and prominent: oscillations were out of phase in different regions because of distinct periods and shapes. Only small ob/ob islets were well synchronised, but sizes of synchronised lean and desynchronised ob/ob islets were markedly overlapped. The occurrence of desynchronisation in clusters of 5 to 50 islet cells from ob/ob mice and not from lean mice further indicates that islet hypertrophy is not the only causal factor. In both types of islets, synchronous [Ca2+]i oscillations were accompanied by oscillations of insulin secretion. In poorly synchronised ob/ob islets, secretion was irregular but followed the pattern of the global [Ca2+]i changes.

Conclusions/interpretation. The regularity of glucose-induced [Ca2+]i oscillations is disrupted in islets from ob/ob mice and this desynchronisation perturbs the pulsatility of insulin secretion. A similar mechanism could contribute to the irregularity of insulin oscillations in Type II (non-insulin-dependent) diabetes mellitus.

Insulin secretion pancreatic islet beta cell cytosolic Ca2+ pulsatility ob/ob mouse 

Copyright information

© Springer-Verlag 2002

Authors and Affiliations

  •  M. Ravier
    • 2
  •  J. Sehlin
    • 3
  •  J. Henquin
    • 1
  1. 1.Unité d'Endocrinologie et Métabolisme, UCL 55.30, avenue Hippocrate 55, 1200 Brussels, Belgium
  2. 2.Unité d'Endocrinologie et Métabolisme, University of Louvain Faculty of Medicine, Brussels, Belgium
  3. 3.Department of Integrative Medical Biology, Section for Histology and Cell Biology, Umea University, Umea, Sweden

Personalised recommendations