Longitudinal evaluation of memory performance and peripheral neuropathy in the Ins2C96Y Akita mice

Ins2(C96Y) Akita mice represent a model of spontaneous early-onset diabetes mellitus, expressing a mutant non-functional isoform of insulin. These mice are characterized by a reduced number of pancreatic beta cells resulting ill hypoinsulinemia and hyperglycemia. We obtained longitudinal measures of morning fasting blood glucose levels and gait performance. Sciatic nerve electrophysiology was also performed and the performance of these mice oil spatial memory tasks was measured longitudinally. We observed a progressive increase in fasting blood glucose levels that was proportionally associated with increased gait disturbances. Diabetes induced a decrease in the sensory nerve conduction velocity up to the age of 40 weeks. Glucose transporter (GLUT) 3 levels were reduced in the hippocampus of the aged Ins2(C96Y) However, we failed to detect any significant deficits during reference, reversal or probe tests in the Morris water maze or in a spontaneous alternation task up to the age of 34 weeks old. We found that LIP to the age of 34 weeks old, uncontrolled hyperglycemia produced peripheral neuropathy and reduced hippocampal GLUT3 levels in the absence of any effect oil spatial memory processing. (C) 2004 Elsevier B.V. All rights reserved.