harmine and Diabetes-Mellitus

β-Cell dysfunction in type 1 and type 2 diabetes is accompanied by a progressive loss of β-cells, and an understanding of the cellular mechanism(s) that regulate β-cell mass will enable approaches to enhance hormone secretion. It is becoming increasingly recognized that enhancement of human β-cell proliferation is one potential approach to restore β-cell mass to prevent and/or cure type 1 and type 2 diabetes. While several reports describe the factor(s) that enhance β-cell replication in animal models or cell lines, promoting effective human β-cell proliferation continues to be a challenge in the field. In this review, we discuss recent studies reporting successful human β-cell proliferation including WS6, an IkB kinase and EBP1 inhibitor; harmine and 5-IT, both DYRK1A inhibitors; GNF7156 and GNF4877, GSK-3β and DYRK1A inhibitors; osteoprotegrin and Denosmab, receptor activator of NF-kB (RANK) inhibitors; and SerpinB1, a protease inhibitor. These studies provide important examples of proteins and pathways that may prove useful for designing therapeutic strategies to counter the different forms of human diabetes.

Topics: Adaptor Proteins, Signal Transducing; Animals; Cell Proliferation; Denosumab; Diabetes Mellitus; Dyrk Kinases; Glycogen Synthase Kinase 3 beta; Harmine; Humans; I-kappa B Kinase; Insulin-Secreting Cells; Monoamine Oxidase Inhibitors; Osteoprotegerin; Phenylurea Compounds; Protein Serine-Threonine Kinases; Protein-Tyrosine Kinases; Receptor Activator of Nuclear Factor-kappa B; RNA-Binding Proteins; Serine Proteinase Inhibitors; Serpins; Tryptamines

An emerging view is that obesity causes metabolic problems when adipose tissue fails to meet the increased demands for fat storage. A study in this issue of Cell Metabolism (Waki et al., 2007) has identified harmine as a proadipogenic small molecule that promotes energy expenditure in white adipose tissue and delays the onset of obesity-associated diabetes.

Topics: Adipogenesis; Adipose Tissue; Animals; Diabetes Mellitus; Harmine; Humans; Mice; Obesity; PPAR gamma