Effects of insulin on long-term potentiation in hippocampal slices from diabetic rats.
OBJECTIVE
Cognitive deficits occur commonly in diabetic patients. It is unclear whether these impairments result from hypoglycaemia during intensive insulin therapy, or from the diabetes itself. The aim of this study was to examine if impaired energy utilization resulting from insulin deficiency contributes to impaired long-term potentiation (reflecting impaired synaptic plasticity). As long-term potentiation is considered a candidate cellular mechanism underlying learning and memory, understanding how diabetes alters long-term potentiation may provide insight into mechanisms producing cognitive deficits in diabetes.


METHODS
Electrophysiologic recordings were used to study long-term potentiation in the CA1 region of hippocampal slices from healthy rats and rats with streptozotocin-induced diabetes.


RESULTS
Long-term potentiation was difficult to induce in slices from diabetic rats in standard recording buffer (contains 10 mmol/l glucose). In slices from diabetic rats, increasing extracellular glucose failed to recover long-term potentiation induction, but 10 mmol/l pyruvate added to standard buffer enabled long-term potentiation induction. Moreover, incubation of slices from diabetic rats with insulin enabled long-term potentiation induction in standard buffer. Acute administration of streptozotocin alone did not impair long-term potentiation in slices from healthy animals, and changing extracellular glucose concentrations over the range of 5 mmol/l to 30 mmol/l did not alter long-term potentiation in slices from control rats.


CONCLUSIONS
These observations suggest that impaired energy utilization from insulin deficiency, rather than the accompanying hyperglycaemia, impair long-term potentiation in diabetes. Impaired hippocampal synaptic plasticity could contribute to learning and cognitive impairment in diabetic patients.
Izumi
Y
Y
Department of Psychiatry, Washington University School of Medicine, 660 S Euclid Avenue, Box 8134, St. Louis, MO 63110, USA. Izumiy@psychiatry.wustl.edu
Yamada
K A
KA
Matsukawa
M
M
Zorumski
C F
CF
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005947:Glucose / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013311:Streptozocin / Q000494:pharmacology
D007328:Insulin; D013311:Streptozocin; D005947:Glucose