RT journal article
T1 Increased Aβ production prompts the onset of glucose intolerance and insulin resistance
A1 Jiménez Palomares, Margarita
A1 Ramos-Rodríguez, Juan José
A1 Lopez-Acosta, Francisco Jose
A1 Pacheco-Herrero, Mar
A1 Lechuga Sancho, Alfonso María
A1 Perdomo, Germán
A1 García Alloza, Mónica
A1 Cozar-Castellano, Irene
A2 BiomedicinaBiotecnología y Salud Pública
K1 type 2 diabetes
K1 Alzheimer's disease
K1 beta-amyloid peptide
K1 APPswe/PS1dE9 mouse
K1 db/db mouse
K1 beta-cell mass
AB Type 2 diabetes (T2D) mellitus and Alzheimer's disease (AD) are two prevalent diseases with comparable pathophysiological features and genetic predisposition. Patients with AD are more susceptible to develop T2D. However, the molecular mechanism linking AD and T2D remains elusive. In this study, we have generated a new mouse model to test the hypothesis that AD would prompt the onset of T2D in mice. To test our hypothesis, we crossed Alzheimer APPswe/PS1dE9 (APP/PS1) transgenic mice with mice partially deficient in leptin signaling (db/+). Body weight, plasma glucose, and insulin levels were monitored. Phenotypic characterization of glucose metabolism was performed using glucose and insulin tolerance tests. beta-Cell mass, islet volume, and islet number were analyzed by histomorphometry. APP/PS1 coexpression in mice with intact leptin receptor signaling did not show any metabolic perturbations in glucose metabolism or insulin sensitivity. In contrast, APP/PS1 coexpression in db/+ mice resulted in nonfasting hyperglycemia, hyperinsulinemia, and hypercholesterolemia without changes in body weight. Conversely, fasting blood glucose and cholesterol levels remained unchanged. Coinciding with altered glucose metabolism, APP/PS1 coexpression in db/+ mice resulted in glucose intolerance, insulin resistance, and impaired insulin signaling. In addition, histomorphometric analysis of pancreata revealed augmented beta-cell mass. Taken together, these findings provide experimental evidence to support the notion that aberrant A beta production might be a mechanistic link underlying the pathology of insulin resistance and T2D in AD.
SN 0193-1849
YR 2012
FD 2012-06
LK http://hdl.handle.net/10498/34806
UL http://hdl.handle.net/10498/34806
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 10-nov-2026