Alzheimer’s disease (AD) is the most reoccurring type of dementia, and remains incurable. Much work has been done to investigate the connections between AD development, type 2 diabetes and insulin receptor signaling abnormalities. Full length amyloid precursor protein (flAPP) is a large transmembrane protein that has significant physiological activities including in utero fetal development. Alpha secretase enzymes cleave flAPP, producing secreted amyloid precursor protein alpha (sAPPα), which has neuroprotective properties, including protection against neuronal apoptosis as well as the induction of neuronal outgrowth. There is no known dedicated receptor for the physiological action of sAPPα. Our data suggest that the physiological actions of sAPPα are a result of the physical interaction between sAPPα and the neuronal insulin receptor. We have shown that sAPPα phosphorylates, and thus activates, the neuronal insulin receptor as well as specific downstream proteins, including insulin receptor substrate (IRS), and protein kinase B (Akt). We have also shown that the observed interaction between sAPPα and neuronal insulin receptors is physical and that sAPPα competes with insulin for the insulin binding site. These findings may have implications for therapies aimed at slowing down the progression of AD through the activation of the insulin receptor pathway, since in neurons, insulin and the insulin receptor pathway are critical to the neuronal health and plasticity.

Proefschrift Universiteit van Amsterdam. / Met lit. opg. - Met samenvatting in het Nederlands.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2006. / Härtill 4 uppsatser.

Thesis (doctoral)--Katholieke Universiteit te Nijmegen.

Thesis (M.S.) -- University of Tennessee, Knoxville, 2006. / Title from title page screen (viewed on Sept. 20, 2006). Thesis advisor: E. Grady Bouge. Vita. Includes bibliographical references.

Proefschrift Maastricht. / Met lit. opg. - Met samenvatting in het Nederlands.

Proefschrift Universiteit Maastricht. / Met bibliogr., lit. opg. - Met samenvatting in het Nederlands.

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AN ABSTRACT OF THE THESIS OF Sarah Sheffer, for the Master of Science degree in Food and Nutrition, presented on September 3, 2009, at Southern Illinois University Carbondale. TITLE: "R. U. A. HEALTHY KID?"- NON-INVASIVE SCREENING FOR RISK FACTORS FOR TYPE 2 DIABETES AT VIENNA GRADE SCHOOL MAJOR PROFESSOR: Dr. Sharon Peterson It is estimated that 1 in 3 children born after the year 2000 will develop some form of diabetes (CDC, 2007). Through Public Act 92-0703, the state of Illinois has started requiring screening for T2DM at the 6th and 9th grade school physicals following the ADA guidelines (IDHS, 2006). The ADA recommends screening children ten and older with a BMI ≥ 85th percentile for two additional risk factors for T2DM (ethnic minority, positive family history of T2DM, hypertension, acanthosis nigricans) (ADA, 2000). While much research has been done, few studies in the U.S. have looked at traditionally "low risk" populations (Sinha 2002, Whitaker 2004, Arslanian 2005). Our study sought to further understand the prevalence of risk factors in a predominantly Caucasian elementary school (K-8 grade). Our study (N=299) found approximately 67% of students to have 1 or more risk factors for T2DM and classified 17 students "at risk" for T2DM. Following Illinois Public Act 92-0703, only 1 student would have been identified "at risk" for T2DM. When comparing "at risk" status, all risk factors except ethnicity were found statistically significant (p< 0.001). Hypertensive "at risk" students were more likely to be morbidly obese (p< 0.001). Our study also found more risk factors as BMI increased.