Insulin and OPLL

Patients with OPLL and diffuse idiopathic skeletal hyperostosis (DISH) have been reported to be obese and have glucose intolerance as well [2-5]. The prevalence of OPLL is high in patients with non-insulin-dependent diabetes mellitus (NIDDM) [3,5]. Because patients with obesity and NIDDM often exhibit impaired action and increased secretion of insulin, there is a possibility that changes in the secretion or action of insulin may play a role in the progression of the disease. Our recent investigation examining the relation between glucose intolerance and the extent of ossification in OPLL patients revealed that the severity of glucose intolerance was not associated with the extent of ossification, but the insulin secretory response was [6] (Fig. 1). It is therefore speculated that the up-

Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 1138655, Japan regulation of insulin production due to impaired insulin action may stimulate osteoprogenitor cells in the ligament to induce ossification.

Insulin initiates cellular responses by binding to its cell-surface receptor tyrosine kinase receptor, which then activates essential adaptor molecule insulin receptor substrates (IRSs) followed by downstream signaling pathways such as phosphatidylinositol-3 kinase (PI3K)/ Akt and mitogen-activated protein kinases (MAPKs). The mammalian IRS family contains at least four members: ubiquitous IRS-1 and IRS-2, adipose tissue-predominant IRS-3, and IRS-4, which is expressed in the thymus, brain, and kidney. We previously reported that IRS-1 and IRS-2 are expressed in bone [14,15]. Although IRS-1 and IRS-2 are known to be essential for intracellular signaling of insulin, these two adaptor molecules have distinct biological roles and are differentially expressed in a variety of cells. Our previous studies revealed that only IRS-1 (not IRS-2) is expressed in the cartilage of the growth plate or the fracture callus, so skeletal growth and fracture healing were impaired in IRS-1-/- mice but were normal in IRS-2-/- mice [16,17]. In bone, IRS-1 is expressed solely in cells of osteoblast lineage, whereas IRS-2 is expressed in cells of both osteoblast and osteoclast lineages [14,15]. These knockout mice exhibited severe osteopenia with distinct mechanisms: IRS-1-/- mice exhibited low bone turnover in which both bone formation and resorption were decreased [14,18], whereas IRS-2-/- mice exhibited an uncoupling status, with decreased bone formation and increased bone resorption [15]. It therefore seems that IRS-1 is important for maintaining bone turnover, and IRS-2 is important for retaining the predominance of anabolic function over catabolic function of osteoblasts (Fig. 2).

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Supplements For Diabetics

All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.

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