Somatostatin promotes glucose generation of Ca2+ oscillations in pancreatic islets both in the absence and presence of tolbutamide

• Many cellular processes, including pulsatile release of insulin, are triggered by increase of cytoplasmic Ca2+. This study examines how somatostatin affects glucose generation of cytoplasmic Ca2+ oscillations in mouse islets in absence and presence of tolbutamide blockade of the K-ATP channels. Ca2+ was measured with dual wavelength microflurometry in isolated islets loaded with the indicator Fura-2. Rise of glucose from 3 to 20 mM evoked introductory lowering of Ca2+ prolonged by activation of somatostatin receptors. During continued superfusion exposure to somatostatin triggered oscillations mediated by periodic increase from the basal level (absence of tolbutamide) or by periodic interruption of an elevated level (presence of tolbutamide). In the latter situation the oscillations were transformed into sustained elevation by activation of muscarinic receptors (acetylcholine) or increase of cyclic AMP (IBMX, 8-bromo-cyclic AMP, forskolin). The observed effect of cyclic AMP raises the question whether high proportions of the glucagon-producing alpha-cells promote steady-state elevation of Ca2+. In support for this idea somatostatin was found to trigger glucose-induced Ca2+ oscillations essentially in small islets that contain very few alpha-cells. The results indicate that somatostatin promotes glucose generation of Ca2+ oscillations with similar characteristics both in the absence and presence of functional K-ATP channels.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Nyckelord

Acetylcholine

Calcium oscillations

Cyclic AMP

Islet size

Somatostatin

Tolbutamide

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