Abstract
Glucose-induced insulin secretion is inhibited by 5-hydroxytryptamine (5HT). In the present studies the specificity of 5HT inhibition of release and the potential biochemical mechanisms involved were investigated. Dose-dependent inhibition of 15 mM glucose-induced secretion was induced by a prior 3 h incubation with 5HT. At the highest 5HT concentration (500 µM) employed, both first and second phase responses to 15 mM glucose were reduced 50–60%. In addition, this level (500 µM) of 5HT virtually abolished 10 mM glucose-induced secretion. In contrast, secretion in response to the protein kinase C activator phorbol 12-myristate 13-acetate (500 nM) was immune to 500 µM 5HT pretreatment. Glucose usage rates were comparable in both control and 500 µM 5HT-pretreated islets. However, the generation of inositol phosphates and the efflux of 3H-inositol from 3H-inositol-prelabeled islets in response to stimulatory glucose were impaired in parallel with insulin secretion. Based on these observations the following conclusions were reached: (1) 5HT impairs glucose-induced insulin release by altering glucose-induced activation of phospholipase C. (2) Biochemical events distal to phospholipase C remain intact despite this proximal biochemical lesion. (3) Amperometric analysis of 5HT release from 5HT-pretreated islets must take into consideration its profound adverse impact on glucose-induced insulin secretion.
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Zawalich, W.S., Tesz, G.J. & Zawalich, K.C. Effects of prior 5-hydroxytryptamine exposure on rat islet insulin secretory and phospholipase C responses. Endocr 23, 11–16 (2004). https://doi.org/10.1385/ENDO:23:1:11
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DOI: https://doi.org/10.1385/ENDO:23:1:11