Disorganization of cytoplasmic Ca(2+) oscillations and pulsatile insulin secretion in islets from ob/ obmice

Diabetologia. 2002 Aug;45(8):1154-63. doi: 10.1007/s00125-002-0883-9. Epub 2002 Jul 4.


Aims/hypothesis: In normal mouse islets, glucose induces synchronous cytoplasmic [Ca(2+)](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/ obmice.

Methods: Intact islets from ob/ ob mice and their lean littermates were used after overnight culture for measurement of [Ca(2+)](i) and insulin secretion.

Results: We observed three types of [Ca(2+)](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 [Ca(2+)](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/ obmice and not from lean mice further indicates that islet hypertrophy is not the only causal factor. In both types of islets, synchronous [Ca(2+)](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 [Ca(2+)](i) changes.

Conclusions/interpretation: The regularity of glucose-induced [Ca(2+)](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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Cytoplasm / metabolism*
  • Glucose / pharmacology
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / anatomy & histology
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Mice
  • Mice, Obese
  • Obesity / metabolism*
  • Organ Size
  • Oscillometry
  • Osmolar Concentration
  • Pulsatile Flow
  • Reference Values
  • Time Factors


  • Insulin
  • Glucose
  • Calcium