Insulin Suppresses the Expression of Amyloid Precursor Protein, Presenilins, and Glycogen Synthase Kinase-3β in Peripheral Blood Mononuclear Cells

• Published in: The journal of clinical endocrinology and metabolism 2011-06, Vol.96 (6), p.1783-1788
• Main Authors: Dandona, Paresh, Mohamed, Islam, Ghanim, Husam, Sia, Chang Ling, Dhindsa, Sandeep, Dandona, Sonny, Makdissi, Antoine, Chaudhuri, Ajay
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Endocrine Research; Endocrinopathies; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Medical sciences; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2010-2961

A low dose insulin infusion in type 2 diabetics significantly reduced amyloid precursor protein expression demonstrating the acute effect of insulin. Objective: Our objective was to determine whether peripheral blood mononuclear cells express amyloid precursor protein (APP) and other mediators involved in the pathogenesis of Alzheimer's disease and whether their expression is suppressed by insulin. Research Design and Methods: Ten obese type 2 diabetic patients were infused with insulin (2 U/h with 100 ml 5% dextrose/h) for 4 h. Patients were also infused with 5% dextrose/h or normal physiological saline for 4 h, respectively, on two other days as controls. Blood samples were obtained at 0, 2, 4, and 6 h. Results: Insulin infusion significantly suppressed the expression of APP, presenilin-1, presenilin-2, and glycogen synthase kinase-3β in peripheral blood mononuclear cells. Dextrose and saline infusions did not alter these indices. Insulin infusion also caused significant parallel reductions in nuclear factor-κB binding activity and plasma concentrations of serum amyloid A and intercellular adhesion molecule-1. Conclusions: A low dose infusion of insulin suppresses APP, presenilin-1, presenilin-2, and glycogen synthase kinase-3β, key proteins involved in the pathogenesis of Alzheimer's disease, in parallel with exerting its other antiinflammatory effects.