BRAIN INSULIN-LIKE GROWTH FACTOR-II MESSENGER-RNA CONTENT IS REDUCED IN INSULIN-DEPENDENT AND NON-INSULIN-DEPENDENT DIABETES-MELLITUS

Diabetic encephalopathy, characterized by structural, electrophysiolog ical, neurochemical, and cognitive abnormalities, is observed in insul in-dependent diabetes mellitus (IDDM) and non-IDDM (NIDDM). Identifica tion of early biochemical lesions potentially may provide clues pointi ng to its pathogenesis. Insulin-like growth factors (IGFs) are neurotr ophic factors that recently have been implicated in the pathogenesis o f diabetic neuropathy. Because IGF-II is the predominant IGF in adult brain, we tested the hypothesis that IGF-II gene expression is decreas ed in the CNS in both IDDM and NIDDM. Brain and spinal cord were isola ted from streptozotocin-diabetic rats, a model of IDDM with weight los s and impaired insulin production. IGF-II mRNA content was measured by northern and slot blots. After 2 weeks of diabetes, IGF-II mRNA conte nt per milligram of tissue wet weight, as well as per unit of poly(A)( +) RNA, declined significantly (p less than or equal to 0.05) in brain and spinal cord. Insulin replacement therapy partially restored IGF-I I mRNA levels in brain, cortex, medulla, and spinal cord. The obese, h yperinsulinemic, and spontaneously diabetic (fa/fa) Zucker rat was use d as a model of NIDDM. Brain weight (p < 0.025) and IGF-II mRNA conten ts (p < 0.01) were significantly decreased in (fa/fa) versus lean nond iabetic (+/?) rats, Therefore, the decline in IGF-II mRNA levels in di abetic brain was independent of the type of diabetes, the direction of change in body weight, and the insulinemic state. We speculate that t his early biochemical lesion may contribute to the development of diab etic encephalopathy.