Effects of GLP-1 [9-36] NH2, a metabolite of GLP-1 [7-36] NH2, on insulin secretion in Hamster Insulinoma Tumor (HIT) cells
GLP-1 [7-36] NH2 (GLP-1) is a potent insulin secretagogue released from the GI tract after meals. GLP-1 is rapidly metabolized to GLP-1 [9-36] NH2 in the circulation, and this truncated form is the predominant GLP-1 species in post-prandial plasma. No biological effects have yet been attributed to GLP-1 [9-36] NH2, but preliminary studies suggest that it antagonizes the effects of GLP-1. In order to characterize the effects of GLP-1 [9-36] NH2 on glucose and GLP-1-stimulated insulin secretion we treated cultured HIT cells with varying amounts of synthetic GLP-1 peptides. HIT cells were incubated in 300 mg% glucose and GLP-1 [9-36] NH2 at concentrations of 0, 0.001, 0.01, 0.1, 1, and 10 μM, both with and without 1 nM GLP-1. As expected, GLP-1 stimulated insulin release (Mean IRI 12.29 ± 141 μU/ml vs. 891 ± 93 μU/ml, p < 0.05) compared to cultures incubated with glucose alone. GLP-1 [9-36] NH2 also increased insulin release, but only at 10 μM (1179 ± 77 μU/ml vs. 891 ± 93 μU/ml, p < 0.05), and not at lower concentrations. The insulinotropic effect of GLP-1 was not inhibited by GLP-1 [9-36] NH2. In fact, when added to 1 nM GLP-1, there was a tendency for 10 μM GLP-1 [9-36] NH2 to increase the insulin response over that seen with GLP-1 alone (1435 ± 197 μU/ml vs. 1229 ± 141 μU/ml). Therefore, GLP-1 [9-36] NH2 does not appear to antagonize the insulinotropic action of GLP-1 as was previously reported. At high concentrations GLP-1 [9-36] NH2 appears to augment glucose-stimulated insulin release. This effect will require further study to determine whether it contributes to glucose homeostasis.
Paty, BW; Teague, J; D'Alessio, DA
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