Fig. 1.

8-pCPT-2′-O-Me-cAMP-AM potentiates 1st- and 2nd-phase glucose-stimulated insulin secretion (GSIS). A: secretion profile for GSIS under conditions of human islet perifusion. Prior to the 30-min time point, islets were perifused with Krebs-Ringer buffer (KRB) containing 3 mM glucose only. This allowed basal insulin secretion to decline to a stable level (data not shown). The glucose concentration was then raised to 10 mM to evoke 1st- and 2nd-phase insulin secretion. Administration of KRB containing 8-pCPT-2′-O-Me-cAMP-AM [10 μM; exchange protein directly activated by cAMP (Epac)-selective cAMP analog (ESCA-AM)] began at the 30-min time point and was continuous until the 60-min time point. ESCA-AM indicates where 8-pCPT-2’-O-Me-cAMP-AM was applied, here and in subsequent figures. Dimethylsulfoxide (DMSO; vehicle control) was included in the KRB for islets not treated with 8-pCPT-2′-O-Me-cAMP-AM. B: quantitative analysis of GSIS potentiated by 8-pCPT-2′-O-Me-cAMP-AM. Summarized are findings obtained using the experimental design illustrated in A, with 2 batches of islets obtained from 2 donors. Insulin secretion is expressed as the normalized area under the curve (AUC) for 1st- and 2nd-phase GSIS, as defined in A. For B, *P < 0.05, t-test.