THE INFLUENCE OF INSULIN-INDUCED HYPOGLYCEMIA ON THE CALCIUM TRANSIENTS ACCOMPANYING REVERSIBLE FOREBRAIN ISCHEMIA IN THE RAT

The primary objective of this study was to explore why preischemic hyp oglycemia, which restricts tissue acidosis during the ischemic insult, does not ameliorate cell damage incurred as a result of transient isc hemia. The question arose whether hypoglycemia (plasma glucose concent ration 2-3 mM) delays resumption of extrusion of Ca2+ from cells durin g recirculation. Measurements of extracellular Ca2+ concentration duri ng forebrain ischemia of 15 min duration proved that this was the case . Thus, normoglycemic animals resumed Ca2+ extrusion upon recirculatio n after a delay of 1.5-2.0 min, and hypoglycemic ones after an additio nal delay which could amount to 3-4 min. We attempted to explore the c ause of this delay. At first sight, the results suggested that resumpt ion of oxidative phosphorylation upon recirculation was substrate limi ted. However, glucose infusion during ischemia or just after recircula tion failed to accelerate Ca2+ extrusion from the cells. A comparison between non-injected and insulin-injected animals at equal plasma gluc ose concentrations suggested that insulin was responsible for the dela y. On analysis, the delay proved to be related to a sluggish recovery of cerebral blood flow. The results suggest that when cell damage is e valuated after transient ischemia in hypo- and normoglycemic subjects, attention should be directed to the period of cell calcium 'overload' . Unobserved differences in the duration of the calcium transient may also confound interpretation of data on the effects of insulin.