SAM PREVENTS IMPAIRMENT OF GLUCOSE-STIMULATED INSULIN-SECRETION CAUSED BY HEXOSE DEPRIVATION OR STARVATION

Succinic acid monomethyl ester (SAM) was recently proposed as an insul inotropic tool in non-insulin-dependent diabetes mellitus. Three model s were now used to investigate whether SAM protects the B-cell against the impairment of glucose-stimulated insulin release caused by either glucose deprivation or starvation. In the first model, preincubation of the islets for 180 min at low glucose concentration in the presence of SAM prevented the decrease in the secretory response to D-glucose otherwise observed during a subsequent incubation. In the second model , an impaired secretory response to D-glucose was observed after 3-day culture at low (2.8 or 5.6 mM) as distinct from high (11.1 mM) hexose concentration and the presence of SAM in the culture medium again pro tected against this anomaly. In the third model, the infusion of SAM f or 3 days to starved rats restored the secretory potential of isolated islets to a level comparable to that otherwise found in fed rats. Thu s, during glucose deprivation or starvation, SAM is indeed able to mai ntain B-cell responsiveness to D-glucose.