, Volume 45, Issue 8, pp 1154-1163

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

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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.

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