Means ± SEM for 3–12 cells at each concentration.

The reason for the absence of [cAMP]pm oscillations in low glucose when glucagon secretion is stimulated is currently unknown. Adenoviruses expressing a fluorescent cAMP biosensor have previously been described (12).
Soluble AC (sAC) is the only isoform that lacks transmembrane domains. Chaque poche contient 5.5g de glucose par ml. B: Stable and reversible [cAMP]pm elevation in response to 100 nmol/L GLP-1 in a β-cell identified by the lack of adrenaline (adr) effect. Reflection of the laser excitation light at the coverglass-medium interface generates an evanescent field within an ∼100 nm zone above the interface, which will excite fluorescent molecules near the plasma membrane of the various islet cells that adhere to the coverslip. A–C: TIRF recordings from mouse islet β-cells (A and C) and a MIN6 cell (B) showing inhibition of glucose-induced [cAMP]pm oscillations by 30 μmol/L KH7 (A and B) and 100 μmol/L DDA (B and C). Programs are tailored to meet specific age levels to ensure the best experience for the individual child. The locations of three putative phosphorylation sites of cAMP-dependent protein kinase (PKA) are indicated as P1, P2, and P3.

As expected, glucagon and GLP-1 evoked cAMP signaling in the islets. It is well accepted that GLP-1 is an inhibitor of glucagon secretion, but the underlying signaling is unclear. Thank you for your interest in spreading the word on PNAS. D: Synchronization of the glucose-induced [cAMP]pm oscillations in two islet β-cells lacking apparent direct contact. Instead, it heterodimerizes with Mlx, a member of the c-myc family, to form a stable heterodimer. In islet β-cells, the cAMP responses to glucagon and GLP-1 were significantly enhanced by high glucose, as expected from earlier biochemical studies (17). The ChREBP gene product identified by Uyeda's (5) laboratory is a strong candidate to fulfill this role.

Scale bar, 10 μm. Glucagon receptor cAMP cascade Phosphorylation reactions Glycogen breakdown Glycogen via phosphorylase Glucose 1-phosphate Glucose 6- phosphate For muscle, the glucose-6-phosphate goes into glycolysis and will generate energy. Glucose has been regarded to only modestly raise islet cAMP, supposedly by amplifying the effect of glucagon (10), but single-cell cAMP recordings have recently shown that glucose alone induces marked elevation of cAMP in MIN6 β-cells (11,12) and primary mouse β-cells (12,13). Like the GLP-1–triggered oscillations of [cAMP]pm, those induced by glucose were often synchronized among β-cells within an islet (Fig.

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