Disorganization of cytoplasmic Ca(2+) oscillations and pulsatile insulin secretion in islets from ob/ obmice
2002 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 45, no 8, 1154-1163 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
Springer-Verlag New York, 2002. Vol. 45, no 8, 1154-1163 p.
insulin secretion, pancreatic islet, beta cell, cytosolic Ca2+, pulsatility, ob/ob mouse
Endocrinology and Diabetes
IdentifiersURN: urn:nbn:se:umu:diva-82647DOI: 10.1007/s00125-002-0883-9ISI: 000177865900010PubMedID: 12189446OAI: oai:DiVA.org:umu-82647DiVA: diva2:662083