Phosphatidylinositol 3,4,5-triphosphate (Ptdlns(3,4,5)-P3), the end product of phosphatidylinositol 3-kinase (P13-K) phosphorylation of polyphosphoinositides, has recently been identified in islets. A rapid, transient increase in PtdIns (3,4,5)P3 levels, which peaks with the acute insulin response, can be induced by insulin secretagogues. We have analyzed the regulatory subunit of P13-K, p85a, as a candidate gene for the high prevalence of NIDDM in Pima Indians. A polymorphism at nucleotide 1020 (G--
