Homologous and heterologous asynchronicity between identified alpha-, beta- and delta-cells within intact islets of Langerhans in the mouse.
1. Using laser scanning confocal microscopy to image [Ca2+]i within intact murine islets of Langerhans, we analysed the [Ca2+]i signals generated by glucose in immunocytochemically identified alpha-, beta- and delta-cells. 2. Glucagon-containing alpha-cells exhibited [Ca2+]i oscillations in the absence of glucose, which petered out when islets were exposed to high glucose concentrations. 3. Somatostatin-containing delta-cells were silent in the absence of glucose but concentrations of glucose as low as 3 mM elicited oscillations. 4. In pancreatic beta-cells, a characteristic oscillatory calcium pattern was evoked when glucose levels were raised from 3 to 11 mM and this was synchronized throughout the beta-cell population. Remarkably, [Ca2+]i oscillations in non-beta-cells were completely asynchronous, both with respect to each other and to beta-cells. 5. These results demonstrate that the islet of Langerhans behaves as a functional syncytium only in terms of beta-cells, implying a pulsatile secretion of insulin. However, the lack of a co-ordinated calcium signal in alpha- and delta-cells implies that each cell acts as an independent functional unit and the concerted activity of these units results in a smoothly graded secretion of glucagon and somatostatin. Understanding the calcium signals underlying glucagon and somatostatin secretion may be of importance in the treatment of non-insulin-dependent diabetes mellitus since both glucagon and somatostatin appear to regulate insulin release in a paracrine fashion.
Nadal
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Institute of Bioengineering and Department of Physiology, Miguel Hernández University, Campus of San Juan, Alicante 03550, Spain. nadal@umh.es
Quesada
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Soria
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D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D005934:Glucagon / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D018613:Microscopy, Confocal; D009991:Oscillometry; D013004:Somatostatin / Q000378:metabolism
D007328:Insulin; D013004:Somatostatin; D005934:Glucagon; D005947:Glucose