PI3K Mediates Islet Neogenesis-Associated Protein Effect upon β-Cell Function

MAIZTEGUI, BÁRBARA; ROMÁN, CAROLINA LISI; BORELLI, MARIA INES; GAGLIARDINO, JUAN JOSÉ

San Francisco

Congreso; 73rd American Diabetes Association Scientific Session; 2013

America Diabetes Association

Islet neogenesis associated protein pentadecapeptide (INGAP-PP) increases insulin secretion (IS) and β-cell mass in normal rats; however, the mechanism by which it produces its effects is not clear. Thus, we studied INGAP-PP effect on IS, glucose (G) metabolism, glucokinase (GK) activity and protein expression and the PI3K pathway in cultured normal rat islets. Islets were isolated by collagenase digestion and cultured for 4 days in RPMI with 2 g/L NaHCO3, 5% FBS, 1% penicillin/streptomycin and 10 mM G, with or w/o 10 µg/ml INGAP-PP. Islets were preincubated in 3 mM G for 45 min and then incubated with 3, 8 and 16 mM G to measure IS, G metabolism (14CO2 and 3H2O production), GK activity (G-6-P production), GK, IR and PI3K protein expression (Western Blot [WB]) and PI3K/IRS-1 complex (immuneprecipitation and WB). We also studied the effect of Wortmannin (W), a PI3K inhibitor (150 and 300 nM) on G-induced IS in both groups. Results: (C vs. INGAP-PP; *p