Species Variation in Pancreatic Islet Monoamine Uptake and Action

Abstract

There are conflicting data in the literature regarding the role of monamines in the secretion of insulin. In order to clarify the contribution that species variation may make to these divergent results, the uptake of serotinin (5-HT), dopamine (DA), and their precursor amino acids, 5-hydroxytryptophan (5-HTP) and L-dopa, into islets was studied. Islets from golden hamsters, rabbits, guinea pigs, and obese, hyperglycemic mice were isolated by the collagenase technique. The islets were incubated in Krebs-Ringer buffer in the presence of 14C-labeled monamines or their precursors. At 30-minute intervals after initiating the study, the incubation mixture was passed through a Millipore filter. The retained islets were disrupted by sonication and the radioactivity counted. The ratio of the uptake of 5-HTP to 5-HT was at least 3:1 in the hamster, guinea pig, and mouse. In the rabbit the ratio was 1:1. A similar relationship was noted for the uptake of L-dopa and DA. The in-vitro results were confirmed by the in-vivo studies, in which hamsters were injected with 14C5-HT or 5-HTP, followed by isolation of the islets. We conclude that there is significant species variation inthe uptake of these monoamines and their precursors.

Association Between 5-Hydroxytryptamine Release and Insulin Secretion

“…DISCUSSION Pancreatic ß-cells from the mouse accumulate both 5-HT (Hellman et al 1972;Mahony & Feldman, 1977) and its precursor 5-HTP (Gylfe et al 1973). When 5-HTP is administered, it is rapidly converted to 5-HT (Gylfe et al 1973) and although this mechanism seems to be general, there are great species differences in the amount of endogenous 5-HT and other biogenic amines (Owman et al 1973).…”

“…These amines are now believed to be normal constituents of all cells producing polypeptide hormones (Owman, Hâkanson & Sundler, 1973). The insulin-releasing ß-cells of mice can readily take up both 5-hydroxytryptamine (5-HT; Hellman, Lernmark, Sehlin & Täljedal, 1972; Mahoney & Feldman, 1977) and its precursor 5-hydroxytryptophan (5-HTP; Gylfe, Hellman, Sehlin & Täljedal, 1973). In the ß-cells, 5-HTP is rapidly converted to 5-HT as judged from the typical fluorescence of the latter amine (Cegrell, Falck & Hellman, 1964;Lernmark, 1971;Tjälve, 1971) or by a quantitative microchromatographic procedure (Gylfe et al 1973).…”

Characteristics of 5‐hydroxytryptamine Transport in Pancreatic Islets

“…Previous studies on the pancreatic islets of non-inbred ob/ob mice suggested an uptake of 5-hydroxytryptamine (5-HT) into the f-cells (Hellman et al, 1972;Mahoney & Feldman, 1977). Differential centrifugation of homogenates from labelled islets showed a preferential localization of radioactive 5-HT in a frac- Islets were incubated for 5 or 120 min in basal medium, containing the concentrations of [3H]-5-HT listed (18.3 to 458 TBq/mol) and 40 gM ['4C]-sucrose (14.1 TBq/mol).…”

“…5-Hydroxytryptamine (5-HT) is a potent inhibitor of glucose-induced insulin secretion (Telib, Raptis, Schroder & Pfeiffer, 1968; Feldman & Lebovitz, 1970;Gagliardino, Nierle & Pfeiffer, 1974), but 5-HT can also stimulate secretion at a substimulatory concentration of glucose (Telib, Raptis, Schroder & Pfeiffer, 1968; Gagliardino, Nierle & Pfeiffer, 1974). Previous studies on the uptake and subcellular distribution of radioactively labelled 5-HT in pancreatic islets suggested that the amine is transported into the islet cells and associated with the insulin secretory granules (Hellman, Lernmark, Sehlin & Taljedal, 1972;Mahoney & Feldman, 1977). Mechanisms for transmembrane transport of 5-HT have been characterized extensively in thrombocytes and synaptosomes.…”

Further Studies on 5‐hydroxytryptamine Transport in Pancreatic Islets and Isolated Β‐cells

“…Many species, including the ob/ob-mouse (Hansen & Hedeskov, 1977), contain endogenous 5-HT in their pancreatic islets. The islets also readily accumulate F 5-HT, either directly from exogenous 5-HT (Hellman et al, 1972;Mahoney & Feldman, 1977;Lind-str6m et al, 1980) or through the uptake of 5hydroxytryptophan (5-HTP) (Ekholm, et al, 1971;Tjailve, 1971), which is rapidly converted intracellularly to 5-HT (Gylfe, Hellman, Sehlin & Taljedal, 1973).…”