title: Islet neogenesis-associated protein (INGAP): the role of its endogenous production as a positive modulator of insulin secretion.
abstract: Islet neogenesis-associated protein (INGAP) is a peptide found in pancreatic exocrine-, duct- and islet- non-β-cells from normal hamsters. Its increase induced by either its exogenous administration or by the overexpression of its gene enhances β-cell secretory function and increases β-cell mass by a combination of stimulation of cell replication and islet neogenesis and reduction of β-cell apoptosis. We studied the potential modulatory role of endogenous INGAP in insulin secretion using two different experimental approaches. Hamster islets transfected with INGAP-small interfering RNA (INGAP-siRNA) were used to study glucose-stimulated insulin secretion (GSIS). In parallel, freshly isolated islets were incubated with high glucose and the same concentration of either a specific anti-INGAP rabbit serum or normal rabbit serum. INGAP-siRNA transfected islets reduced their INGAP mRNA and protein content by 35.1% and 47.2%, respectively whereas GSIS decreased by 25.8%. GSIS by transfected islets attained levels comparable to those recorded in control islets when INGAP pentadecapeptide (INGAP-PP) was added to the culture medium. INGAP antibody in the medium decreased significantly GSIS in a dose-dependent manner. These results indicate that endogenous INGAP plays a "physiological" positive modulatory role in insulin secretion, supporting its possible use in the treatment of prediabetes and Type 2 diabetes.
authors.affiliation: CENEXA, Center of Experimental and Applied Endocrinology, National University of La Plata, La Plata National Research Council, PAHO/WHO Collaborating Center, School of Medical Sciences, 1900 La Plata, Argentina. Electronic address: leflores@cenexa.org.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Flores
authors.affiliation: CENEXA, Center of Experimental and Applied Endocrinology, National University of La Plata, La Plata National Research Council, PAHO/WHO Collaborating Center, School of Medical Sciences, 1900 La Plata, Argentina.
authors.forename: Héctor
authors.initials: H
authors.lastname: Del Zotto
authors.affiliation: CENEXA, Center of Experimental and Applied Endocrinology, National University of La Plata, La Plata National Research Council, PAHO/WHO Collaborating Center, School of Medical Sciences, 1900 La Plata, Argentina.
authors.forename: Florencia
authors.initials: F
authors.lastname: Fragapane
authors.affiliation: CENEXA, Center of Experimental and Applied Endocrinology, National University of La Plata, La Plata National Research Council, PAHO/WHO Collaborating Center, School of Medical Sciences, 1900 La Plata, Argentina.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Maiztegui
authors.affiliation: CENEXA, Center of Experimental and Applied Endocrinology, National University of La Plata, La Plata National Research Council, PAHO/WHO Collaborating Center, School of Medical Sciences, 1900 La Plata, Argentina.
authors.forename: Carolina L
authors.initials: CL
authors.lastname: Román
authors.affiliation: Department of Physiology and Biophysics, Institute of Biology, State University of Campinas, UNICAMP, Campinas 13083-970, Brazil.
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Boschero
authors.affiliation: CENEXA, Center of Experimental and Applied Endocrinology, National University of La Plata, La Plata National Research Council, PAHO/WHO Collaborating Center, School of Medical Sciences, 1900 La Plata, Argentina.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Gagliardino
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D008647:Mesocricetus; D000073718:Pancreatitis-Associated Proteins; D010446:Peptide Fragments / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D016207:Cytokines; C500438:INGAP peptide; D007328:Insulin; D000073718:Pancreatitis-Associated Proteins; D010446:Peptide Fragments; C000612141:REG3A protein, human
keywords: Hamsters; INGAP; Insulin secretion; Isolated islets; siRNA