Effects of prior 5-hydroxytryptamine exposure on rat islet insulin secretory and phospholipase C responses

• Published in: Endocrine Vol. 23; no. 1; p. 11
• Main Authors: Zawalich, Walter S, Tesz, Gregory J, Zawalich, Kathleen C
• Format: Journal Article
• Language: English
• Published: United States 01.02.2004
• Subjects: Animals; Enzyme Activation - drug effects; Glucose - metabolism; Glucose - pharmacology; Inositol Phosphates - metabolism; Insulin - metabolism; Insulin Secretion; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; Male; Rats; Rats, Sprague-Dawley; Secretory Rate - drug effects; Serotonin - pharmacology; Tetradecanoylphorbol Acetate - pharmacology; Type C Phospholipases - metabolism
• ISSN: 1355-008X; 1559-0100
• DOI: 10.1385/endo:23:1:11

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 microM) employed, both first and second phase responses to 15 mM glucose were reduced 50-60%. In addition, this level (500 microM) 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 microM 5HT pre-treatment. Glucose usage rates were comparable in both control and 500 microM 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.