Acute Exposure of the Mediobasal Hypothalamus to Amyloid-β25-35 Perturbs Hepatic Glucose Metabolism

Patients with Alzheimer's disease (AD) have a higher risk for developing insulin resistance and diabetes. Amyloid plaques, a hallmark of AD, are composed of amyloid-beta (A beta). Because the mediobasal hypothalamus controls hepatic glucose production, we examined the hypothesis that its exposure to A beta perturbs the regulation of glucose metabolism. The infusion of A beta(25-35), but not its scrambled counterpart, into the mediobasal hypothalamus of young rats, increased circulating glucose as a consequence of enhanced hepatic glucose production during pancreatic clamp studies. These findings suggest a link between AD and alterations of glucose metabolism.