In order to determine whether microvascular blood flow is important in the regulation of intra-islet cellular interactions, rat pancreata were isolated and perfused in vitro, both anterogradely or retrogradely, with and without anti-insulin or antisomatostatin y-globulin. Expressed as percent change, anterograde infusion of insulin antibody increased efflux concentrations of glucagon (110±20%, P < 0.0005) and somatostatin (2,112±73%, P < 0.0005) above their respective control. Retrograde infusion of insulin antibody did not affect efflux concentrations of glucagon (P < 0.50) or somatostatin (P < 0.50). The anterograde infusion of anti-somatostatin antibody had no effect upon insulin (P < 0.50) or glucagon (P < 0.50) efflux concentrations, whereas retrograde anti-somatostatin antibody infusion produced immediate increases in efflux concentrations of both insulin (115±33%, P < 0.0005) and glucagon (77±8%, P < 0.0005).These results strongly suggest that (a) the vascular compartment is important in the regulation of intra-islet cellular interactions and further suggest that (b) the order of islet cellular perfusion and interaction is from the B cell core outward to the mantle, and (c) the mantle is further subordered with the majority of D cells downstream or distal to the majority of A cells. Thus, in the vascular compartment, B cells inhibit A-cell secretion and A cells stimulate D-cell secretion. IntroductionThe recognition that the islet is not a random or homogeneous mixture of cell types, but is an ordered structure containing

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Employing a preparation of rat islet mitochondria, phosphoenolpyruvate has been shown to interact with the mitochondrial adenine nucleotide translocase. Thus, phosphoenolpyruvate inhibited mitochondrial uptake of [14C]ADP and exchanged with intramitochondrial [14C]ATP. A concentration-dependent inhibition of islet mitochondrial 45Ca2+ accumulation was seen when mitochondria were exposed to phosphoenolpyruvate with half-maximal inhibition observed at a phosphoenolpyruvate concentration of 0.2 mM. In experiments employing whole islets, phosphoenolpyruvate content was shown to be significantly elevated at both 1 and 30 min after an increase in the medium glucose concentration from 2 to 20 mM. In these experiments, the estimated islet concentrations of phosphoenolpyruvate fell in the range of maximal sensitivity of the islet adenine nucleotide translocase to phosphoenolpyruvate-induced inhibition of Ca2+ accumulation. It is concluded that increased concentrations of islet phosphoenolpyruvate resulting from increased extracellular glucose concentration may act to trigger or promote glucose-stimulated insulin secretion by modifying the distribution of Ca2+ between the islet cytosolic and mitochondrial compartments in a transport reaction catalyzed by the adenine nucleotide translocase.