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 hypoglycemia, which restricts tissue acidosis during the ischemic insult, does not ameliorate cell damage incurred as a result of transient ischemia. The question arose whether hypoglycemia (plasma glucose concentration 2-3 mM) delays resumption of extrusion of Ca2+ from cells during recirculation. Measurements of extracellular Ca2+ concentration during forebrain ischemia of 15 min duration proved that this was the case. Thus, normoglycemic animals resumed Ca2+ extrusion upon recirculation after a delay of 1.5-2.0 min, and hypoglycemic ones after an additional delay which could amount to 3-4 min. We attempted to explore the cause of this delay. At first sight, the results suggested that resumption of oxidative phosphorylation upon recirculation was substrate limited. However, glucose infusion during ischemia or just after recirculation failed to accelerate Ca2+ extrusion from the cells. A comparison between non-injected and insulin-injected animals at equal plasma glucose concentrations suggested that insulin was responsible for the delay. On analysis, the delay proved to be related to a sluggish recovery of cerebral blood flow. The results suggest that when cell damage is evaluated 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.
D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000097:blood; D005947:Glucose / Q000494:pharmacology; D007003:Hypoglycemia / Q000139:chemically induced / Q000378:metabolism*; D007262:Infusions, Intravenous; D007328:Insulin / Q000009:adverse effects*; D017136:Ion Transport; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D010085:Oxidative Phosphorylation; D016548:Prosencephalon / Q000098:blood supply*; D051381:Rats; D017208:Rats, Wistar
D007328:Insulin; D005947:Glucose; D002118:Calcium