Effects and Underlying Mechanisms of Bioactive Compounds on Type 2 Diabetes Mellitus and Alzheimer's Disease

Abstract

Type 2 diabetes mellitus is a complicated metabolic disorder characterized by hyperglycemia and glucose intolerance. Alzheimer's disease is a progressive brain disorder characterized by a chronic loss of cognitive and behavioral function. Considering the shared characteristics of both diseases, common therapeutic and preventive agents may be effective. Bioactive compounds such as polyphenols, vitamins, and carotenoids found in vegetables and fruits can have antioxidant and anti-inflammatory effects. These effects make them suitable candidates for the prevention or treatment of diabetes and Alzheimer's disease. Increasing evidence from cell or animal models suggest that bioactive compounds may have direct effects on decreasing hyperglycemia, enhancing insulin secretion, and preventing formation of amyloid plaques. The possible underlying molecular mechanisms are described in this review. More studies are needed to establish the clinical effects of bioactive compounds.

Figure 1

Functions of bioactive compounds in T2DM and AD pathogenesis. (1) Shared characteristics of T2DM and AD including insulin resistance, inflammation, and oxidative stress. (2) Some bioactive compounds can ameliorate hyperglycemia by activating AMPK, increasing GLUT4 translocation, inhibiting PEPCK and G6Pase activities, or activating SIRT1. (3) Some bioactive compounds can preserve functional β-cell mass by increasing β-cell proliferation or decreasing apoptosis. (4) Through activation of the PI3K/Akt pathway, some bioactive compounds improved insulin resistance. (5) Bioactive compounds attenuate oxidative stress via reducing NO, iNOS, and COX-2 levels or/and increasing the expression of antioxidant enzymes. (6) Most bioactive compounds could ameliorate inflammation which in turn improves T2DM and AD pathology. (7) Bioactive compounds can decrease Aβ production or assemble them into nontoxic aggregates, thereby decreasing formation of amyloid plaques. (8) Some bioactive compounds reduce NFT levels by inhibiting tau hyperphosphorylation. References: [, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , –196, 200, 204, 215, 217, 227, 231, 234].