The invention relates to the diagnosis of the pre-diabetic state and processes underlying development of diabetic state way before blood glucose levels are abnormaln and diabetes clinical symptoms occur. This may be done using the relative proportion of the level of the Wnt4 and Wnt3a proteins in blood plasma.
Briefly, in prediabetic state insulin resistant tissues (skeletal muscle and adipose tissue) produce and secrete into the blood plasma less inhibitor (Wnt4) and more activator (Wnt3a) of canonical Wnt signaling pathway what leads to upregulation of Wnt signaling in pancreatic β- cells and cardiomyocytes through an endocrine manner. Activated Wnt pathway triggers adaptation of β- cells to the systemic insulin resistance by increasing insulin secretion and β- cells proliferation rate. Simultaneously, increased Wnt signalling in cardiomyocytes leads to upregulation of hypertrophic genes, ANP and BNP, and initiate cardiomyocyte hypertrophy, a known hallmark of diabetic cardiomyopathy. In diabetic state insulin resistant tissues produce and secrete into blood plasma more inhibitor (Wnt4) and less activator (Wnt3a) of canonical Wnt signaling pathway what has impact on downregulation of Wnt signalling in pancreatic β- cells. Reduction of Wnt pathway activation negatively affect β- cell adaptation to the systemic insulin resistance and leads to pancreatic islet dysfunction. Thus, the relative proportion of the level of the Wnt4 and Wnt3a proteins in blood plasma might be used as biomarker of pre-diabetic and diabetic states. The present invention also relates to the use of Wnt4 and Wnt3a as therapeutic targets for alleviating the effects of diabetic beta cell insufficiency, as well as cardiac myopathy.
Patents were granted in USA and Europe and the European patent was validated in France, Germany, Poland, Spain, Switzerland, United Kingdom. Nencki Institute is the sole applicant.
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