Glucose-dependent insulinotropic polypeptide stimulated insulin release from a tumor-derived beta-cell line (beta TC3).
The beta TC3 tumor cell line was examined for the presence of functional glucose-dependent insulinotropic polypeptide (GIP) receptors. Increasing amounts of natural porcine GIP decreased the binding of HPLC-purified [125I]GIP to beta TC3 cells in a concentration-dependent manner. Displacement of GIP was significant at concentrations as low as 500 pM, and the radioligand was fully displaced at 100 nM. GIP(1-30) produced a displacement of [125I]GIP comparable with that produced by GIP(1-42), and glucagon yielded 20% displacement at a concentration of 1 microM but was without effect at 100 mM. Incubation of beta TC3 cells in the presence of glucose concentrations of 2-20 mM yielded a concentration-dependent stimulation of immunoreactive insulin (IRI) release. GIP and glucagon-like peptide-I(7-36) amide (tGLP-I) at concentrations of 1 nM or greater significantly stimulated IRI release in the presence of 2 mM glucose. The threshold glucose concentration for GIP-stimulated IRI release from beta TC3 cells was 0.5 mM, and maximal potentiation of IRI release by GIP occurred at 5 mM glucose. Somatostatin significantly inhibited GIP-stimulated IRI release in the presence of 5 mM glucose. It is concluded that beta TC3 cells have functional GIP receptors and may provide a useful model for the study of IRI secretion at the cellular level.
Kieffer
T J
TJ
Department of Physiology, University of British Columbia, Vancouver, Canada.
Verchere
C B
CB
Fell
C D
CD
Huang
Z
Z
Brown
J C
JC
Pedersen
R A
RA
D000818:Animals; D005749:Gastric Inhibitory Polypeptide / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D005934:Glucagon / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D007457:Iodine Radioisotopes; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism; D013004:Somatostatin / Q000494:pharmacology; D013552:Swine; D014407:Tumor Cells, Cultured
D007328:Insulin; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D011498:Protein Precursors; D011956:Receptors, Cell Surface; D011964:Receptors, Gastrointestinal Hormone; D013004:Somatostatin; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose