Stimulatory effects of glucagon-like peptides on human insulinoma cells and insulin-releasing clonal RINm5F cells.
Insulin-releasing effects of glucagon-like peptides, glucagon and various nutrients were examined using tumour cells from a freshly resected human insulinoma and RINm5F cells. Insulin release by human insulinoma cells or RINm5F cells was not affected by 16.7 mM glucose. Both cell types exhibited secretory responses to 20 mM alanine, 25 mM K+ and 7.6 mM Ca2+. Insulin release by human insulinoma cells was enhanced at 2 x 10(-7) M by glucagon, GLP-1[1-37], GLP-1[7-36] and its N- and C-terminal fragments GLP-1[7-14] and GLP-1[31-37]. The intact peptides (2 x 10(-6)-2 x 10(-12) M) also stimulated insulin release by RINm5F cells, but neither of the fragments enhanced secretion. The cyclic AMP content of human insulinoma cells and RINm5F cells was increased by glucagon. GLP-1[7-36] (2 x 10(-8)-2 x 10(-10) M) increased cyclic AMP in RINm5F cells, but no additional effects were noted in these or human insulinoma cells. These results suggest that GLP-1[7-36] stimulates insulin release by a direct action on human and rat B-cells, partly involving modulation of intracellular cyclic AMP.
Flatt
P R
PR
Department of Biological and Biomedical Sciences, University of Ulster, Coleraine, UK.
Shiber
O
O
Hampton
S M
SM
Marks
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V
D000328:Adult; D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D005934:Glucagon / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007340:Insulinoma / Q000378:metabolism*; D007700:Kinetics; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
D007328:Insulin; D010446:Peptide Fragments; D005934:Glucagon; D000242:Cyclic AMP; D005947:Glucose