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. 2014 Jun-Aug:192-193:30-4.
doi: 10.1016/j.regpep.2014.08.003. Epub 2014 Aug 23.

Islet neogenesis-associated protein (INGAP): the role of its endogenous production as a positive modulator of insulin secretion

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Islet neogenesis-associated protein (INGAP): the role of its endogenous production as a positive modulator of insulin secretion

Luis E Flores et al. Regul Pept. 2014 Jun-Aug.

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.

Keywords: Hamsters; INGAP; Insulin secretion; Isolated islets; siRNA.

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