Researchers have proposed that amyloid precursor protein 17 peptide (APP17 peptide), an active fragment of amyloid precursor protein (APP) in the nervous system, has therapeutic effects on neurodegeneration. Diabetic encephalopathy (DE) is a neurological disease caused by diabetes. Here we use multiple experimental approaches to investigate the effect of APP17 peptide on changes in learning behavior and glycol metabolism in rats. It was found that rats with DE treated by APP17 peptide showed reversed behavioral alternation. The [18F]-FDG-PET images and other results all showed that the APP17 peptide could promote glucose metabolism in the brain of the DE rat model. Meanwhile, the insulin signaling was markedly increased as shown by increased phosphorylation of Akt and enhanced GLUT4 activation. Compared with the DE group, the activities of SOD, GSH-Px, and CAT in the rat hippocampal gyrus were increased, while MDA decreased markedly in the DE + APP17 peptide group. No amyloid plaques in the cortex and the hippocampus were detected in either group, indicating that the experimental animals in the current study were not suffering from Alzheimer’s disease. These results indicate that APP17 peptide could be used to treat DE effectively. 1. Introduction Diabetes mellitus, or simply diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the pancreas does not produce enough insulin or because cells do not respond to the insulin that is produced [1–3]. Insulin causes cells in the liver, skeletal muscles, and fat tissue to absorb glucose from the blood. In the liver and skeletal muscles, glucose is stored as glycogen, and in fat cells (adipocytes) it is stored as triglycerides [4, 5]. Diabetes can be divided into 3 main types: Type 1 diabetes, which results from the inability to produce insulin; Type 2 diabetes, resulting from insulin resistance; and gestational diabetes [6–8]. Type 2 diabetes, without proper treatment, can cause many complications, including hypoglycemia, diabetic ketoacidosis, and nonketotic hyperosmolar coma [9]. Adequate treatment of diabetes is consequently vital. Diabetic encephalopathy (DE) is caused by diabetes [10]. The complications of DE include memory loss, dementia, coma, seizures, and finally death. The defects in patients include lethargy, poor judgment and coordination of limbs, dementia, and muscle twitching [11]. Amyloid precursor protein (APP) is a transmembrane protein with six isoforms in the central nervous system (CNS), of which APP-695 is the most important [12, 13]. Hydrolysis of
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