Effects of insulin under normal and low glucose on retinal electrophysiology in the perfused cat eye.
OBJECTIVE
To investigate the short-term effects of fast-acting insulin on the electroretinogram-b-wave, optic nerve response, standing potential, and flow rate in the arterially perfused cat eye under normal conditions and during low glucose levels.


METHODS
Enucleated cat eyes were perfused with a glucose- and insulin-free tissue culture medium, to which glucose was applied at normal (5.5 mM) and reduced (2 and 1 mM) concentrations. Photic stimulation was performed in the rod-matched intensity range before, during, and after insulin application at postprandial (5 ng/ml) and at 10 and 20 x higher concentrations.


RESULTS
Insulin failed to affect retinal signals at normal glucose levels. However, insulin enhanced the low glucose-induced decrease in rod-driven b-wave amplitude (P < 0.05 at 2 mM; P < 0.01 at 1 mM) without affecting the corresponding changes in the optic nerve response. The standing potential increased by as much as 0.75 mV in response to insulin. The perfusate flow rate was not altered by insulin.


CONCLUSIONS
Insulin was not required for normal retinal function as observed during 10 hours of perfusion. The differential responsiveness to insulin under low glucose of the b-wave versus the optic nerve response is thought to reflect suppression of glucose use by Müller (glial) cells rather than neuromodulation, as the neuronal optic nerve response is unaffected. The postulated insulin sensitivity of Müller cells (changes in b-wave amplitude) indicates a possible difference in the mechanism of glucose metabolism of glia versus neurons. The electrophysiological effect of insulin under low glucose suggests its passage across the blood-retina barrier. The increase in the standing potential is likely to be a receptor-mediated retinal pigment epithelium effect. These results provide evidence in the retina for the reported multifunctional nature of the insulin receptor.
Lansel
N
N
Department of Ophthalmology, University Hospital, Zurich, Switzerland.
Niemeyer
G
G
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001813:Blood-Retinal Barrier / Q000502:physiology; D002415:Cats; D004596:Electroretinography; D005260:Female; D005947:Glucose / Q000008:administration & dosage*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007261:Infusions, Intra-Arterial; D007328:Insulin / Q000494:pharmacology*; D009880:Ophthalmic Artery / Q000502:physiology; D009900:Optic Nerve / Q000187:drug effects / Q000502:physiology; D010477:Perfusion; D010775:Photic Stimulation; D011972:Receptor, Insulin / Q000502:physiology; D012160:Retina / Q000187:drug effects / Q000502:physiology*
D007004:Hypoglycemic Agents; D007328:Insulin; D011972:Receptor, Insulin; D005947:Glucose