The role of parathyroid hormone-related protein (PTHrP) in the pathophysiology of diabetes mellitus.
Type 2 diabetes is characterized by hyperglycemia resulting from insulin resistance in the setting of inadequate beta-cell compensation. Impaired beta-cell function and possibly beta-cell mass appear to be reversible, particularly at early stages of the disease. Pancreatic beta-cells possess the potential to greatly expand their function and mass in both physiologic and pathologic states by several mechanisms, including hypertrophy and proliferation of existing beta-cells, increased insulin production and secretion, and formation of new beta-cells from progenitor cells. Recently a large number of factors controlling the differentiation of beta-cells has been identified and among them the parathyroid hormone-related protein (PTHrP) emerged as a strong candidate in beta-cell survival. In this review, we will highlight our current knowledge in PTHrP physiology implicating its role into the mechanisms of beta-cell mass regulation and consequently in diabetes. Further research into mechanisms will reveal the key modulators of beta-cell failure and thus identify possible novel therapeutic targets.
Legakis
Ioannis
I
Department of Endocrinology, Henry Dunant Hospital, Athens, Greece. ilegak@med.uoa.gr
D000818:Animals; D003920:Diabetes Mellitus / Q000378:metabolism* / Q000503:physiopathology*; D006801:Humans; D010179:Pancreas / Q000473:pathology / Q000503:physiopathology; D010281:Parathyroid Hormone / Q000737:chemistry / Q000378:metabolism; D044162:Parathyroid Hormone-Related Protein / Q000737:chemistry / Q000378:metabolism*; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000378:metabolism; D013329:Structure-Activity Relationship
D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D044168:Receptor, Parathyroid Hormone, Type 1