title: Effects of High Glucose Levels and Glycated Serum on GIP Responsiveness in the Pancreatic Beta Cell Line HIT-T15.
abstract: Glucose-dependent insulinotropic peptide (GIP) is an incretin hormone produced in the gastrointestinal tract that stimulates glucose dependent insulin secretion. Impaired incretin response has been documented in diabetic patients and was mainly related to the inability of the pancreatic beta cells to secrete insulin in response to GIP. Advanced Glycation End Products (AGEs) have been shown to play an important role in pancreatic beta cell dysfunction. The aim of this study is to investigate whether the exposure to AGEs can induce GIP resistance in the pancreatic beta cell line HIT-T15. Cells were cultured for 5 days in low (CTR) or high glucose (HG) concentration in the presence of AGEs (GS) to evaluate the expression of GIP receptor (GIPR), the intracellular signaling activated by GIP, and secretion of insulin in response to GIP. The results showed that incubation with GS alone altered intracellular GIP signaling and decreased insulin secretion as compared to CTR. GS in combination with HG reduced the expression of GIPR and PI3K and abrogated GIP-induced AKT phosphorylation and GIP-stimulated insulin secretion. In conclusion, we showed that treatment with GS is associated with the loss of the insulinotropic effect of GIP in hyperglycemic conditions.
authors.affiliation: Department of Internal Medicine, University of Genoa, Viale Benedetto XV, 16143 Genoa, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Puddu
authors.affiliation: Department of Internal Medicine, University of Genoa, Viale Benedetto XV, 16143 Genoa, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Sanguineti
authors.affiliation: Department of Internal Medicine, University of Genoa, Viale Benedetto XV, 16143 Genoa, Italy ; Division of Cardiology, Department of Medicine, Geneva University Hospitals, Faculty of Medicine, Foundation for Medical Researches, 64 Avenue de la Roseraie, 1211 Geneva, Switzerland ; Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, 4 Rue Gabrielle-Perret-Gentil, 1205 Geneva, Switzerland.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Montecucco
authors.affiliation: Department of Internal Medicine, University of Genoa, Viale Benedetto XV, 16143 Genoa, Italy.
authors.forename: Giorgio Luciano
authors.initials: GL
authors.lastname: Viviani
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D015153:Blotting, Western; D002460:Cell Line; D015536:Down-Regulation; D005749:Gastric Inhibitory Polypeptide / Q000037:antagonists & inhibitors* / Q000097:blood / Q000235:genetics / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000097:blood / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008647:Mesocricetus; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011964:Receptors, Gastrointestinal Hormone / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D001786:Blood Glucose; D017127:Glycation End Products, Advanced; D007328:Insulin; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011964:Receptors, Gastrointestinal Hormone; D011994:Recombinant Proteins; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; C041086:gastric inhibitory polypeptide receptor; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt