Biphasic insulin release as the expression of combined inhibitory and potentiating effects of XXXX .

@entity35 @entity369 @entity734 @entity413
The dynamics of insulin release were investigated in vitro in order to determine the regulatory processes governing its biphasic shape. When subjected to a square wave @entity413 stimulation, the isolated perfused @entity35 pancreas responded with typical biphasic insulin release. Both the duration of the nadir between the two phases and the slope of recovery of insulin release during second-phase secretion exhibited @entity413 dose dependency. Successive 40-min stimuli with @entity413 (8.3 and 16.7 mM), separated by a 20-min rest period, resulted in 2.6- 3.3-fold potentiation of the early phase insulin release rate, previously described as @entity413 -primed @entity734 ( @entity734 ) of insulin secretion. A linear relationship (r = 0.89, P less than 0.001) was observed between the degree of @entity734 and the slope of second-phase insulin release. Successive short stimuli with @entity413 (5-10 min long, 5-10 min apart; 6.9, 8.3, and 16.7 mM) resulted in the inhibition of the response to the second stimulus; this effect was termed @entity734 ( @entity734 ) of insulin release. @entity369 also induced @entity734 ; this was completely overcome by synergistic interaction with @entity413 (8.3 mM). The @entity413 - @entity369 interaction was utilized to demonstrate that the interphasic nadir of insulin release was the expression of @entity734 . Thus, introduction of an @entity369 stimulus during the nadir in @entity413 -induced insulin release abolished the silent phase, the secretion rate reaching the level expected for the combined @entity413 - @entity369 stimulus. However, the continued presence of @entity734 could be demonstrated by removal of the @entity369 stimulus, at which time, despite ongoing @entity413 stimulation, insulin secretion was markedly inhibited. These observations support the concept that the biphasic dynamics of insulin release is the net expression of three regulatory processes: 1) the acute stimulus-secretion coupling system, best observed as the immediate, first-phase response to a stimulus; 2) @entity734 of insulin release, a relatively rapid signal responsible for the silent period; and 3) @entity734 of insulin release, a slow rising signal responsible for recovery from the silent phase, building up the second-phase of secretion.
