Diabetes Mellitus as Dysfunction of Interactions Among all Organs: “Ominous Orchestra of Organs”

Epidemiological evidence has established a link among hyperlipidemia, visceral obesity, osteoporosis, and cardiovascular diseases. We have recently proposed a hypothesis that the associations of those disorders are based on interactions of the three organs, i.e. the bone, adipose, and vascular tissues, possibly through multiple actions of several humoral factors and/or transcription factors. We call this unified hypothesis ‘osteo-lipo-vascular interactions’, which may be explained by the common origin of the cells in each organ, such as mesenchymal stem cells or macrophages. Several groups proposed similar hypotheses. On the other hand, there have been accumulating evidences which indicate that there exist hitherto unknown various interactions between many organs, such as hypothalamus-liver, fat-liver, liver-muscle, intestine-pancreas, kidney-heart and so on. Therefore, it seems insufficient to consider only the interactions among several organs, and the standpoint of considering interactions among all organs may be warranted, especially in order to understand the pathogenesis of metabolic syndrome, insulin resistance and type 2 diabetes. We here propose a hypothesis that the abnormal interactions of all organs (“Ominous Orchestra of Organs”) underlies the pathogenesis of type 2 diabetes. It is to be elucidated which of the “players” or the “conductor” may be mainly responsible for disharmony of the orchestra.