The effect of topical insulin on the release of excitotoxic and other amino acids from the rat cerebral cortex during streptozotocin-induced hyperglycemic ischemia.

Abstract

Insulin has been demonstrated to be neuroprotective in brain and spinal cord ischemia. The mechanism of neuroprotection may involve alterations in metabolism, protein synthesis or uptake of GABA by astrocytes. Conversely, hyperglycemia increases the extent of neurologic damage observed during ischemia/reperfusion. Diabetic patients are 2-4 times more likely to suffer a stroke as normoglycemic patients and they also have worsened neurologic outcome. Determining if insulin, which many diabetics already use as therapy, can be neuroprotective, would be a possible means of alleviating the detrimental outcome from diabetic stroke. This study looked at the relationship between topically administered insulin (1 mIU insulin/ml and 100 mIU insulin/ml) during a four vessel occlusion model of global ischemia and the release of amino acids, especially glutamate, from the cortex in streptozotocin (STZ)-treated rats. The rats were utilized either 5-7 days (ASTZ) or 4-6 weeks (CSTZ) after a single STZ injection. In the ASTZ animals both doses of insulin increased the amount of the excitotoxic amino acids, aspartate and glutamate, released during reperfusion and the higher dose also increased the levels of taurine and GABA during reperfusion. In the CSTZ animals, both doses of insulin increased the amount of excitotoxic amino acids during reperfusion and the lower dose increased GABA levels released during reperfusion. The differences between the ACTZ and CSTZ animals may be due to metabolic differences in the utilization of glucose. Insulin may act as a neuroprotectant by increasing extracellular GABA resulting in neuroinhibition.

• Authors: L L Guyot, F G Diaz, M H O'Regan, D Song, J W Phillis
• Journal: Brain research (Brain Res) Vol. 872 Issue 1-2 Pg. 29-36 (Jul 28 2000) ISSN: 0006-8993 [Print] Netherlands
• PMID: 10924672 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Blood Glucose
• Excitatory Amino Acids
• Insulin
• Taurine
• Aspartic Acid
• Lactic Acid
• Glutamic Acid
• gamma-Aminobutyric Acid

Topics

• Administration, Topical
• Animals
• Aspartic Acid (metabolism)
• Blood Glucose
• Brain Ischemia (etiology, metabolism)
• Cerebral Cortex (blood supply, drug effects, metabolism)
• Diabetes Mellitus, Experimental (blood, complications)
• Dose-Response Relationship, Drug
• Electroencephalography
• Excitatory Amino Acids (metabolism)
• Extracellular Space (metabolism)
• Glutamic Acid (metabolism)
• Hyperglycemia (blood, chemically induced)
• Insulin (administration & dosage)
• Lactic Acid (blood)
• Male
• Rats
• Rats, Sprague-Dawley
• Reperfusion
• Taurine (metabolism)
• gamma-Aminobutyric Acid (metabolism)