Cardiotrophin 1 protects beta cells from apoptosis and prevents streptozotocin-induced diabetes in a mouse model.

AIMS/HYPOTHESIS: Cardiotrophin 1 (CT-1) is a recently described cytokine originally isolated from the heart where it has been shown to play an important role in apoptotic protection of cardiomyocytes and heart hypertrophy. Its beneficial properties have also been described in other organs such as liver and neuromuscular tissue. In the present study, we investigated whether CT-1 can confer protection against pro-apoptotic stimuli in pancreatic beta cells, and its role in insulin secretion and diabetes development. METHODS: The effects of CT-1 on apoptosis and function were studied using MIN6B1 cells and freshly isolated murine pancreatic islets. The impact on the development of diabetes was evaluated in Ct1-null (Ct1 (-/-)) mice (the gene Ct1 is also known as Ctf1) using two streptozotocin (STZ)-induced models of diabetes. RESULTS: CT-1 has a protective effect in MIN6B1 cells and murine islets under the pro-apoptotic stimulus of serum deprivation, which correlates with the expression of B cell lymphoma-extra large, or following exposure to a mixture of cytokines. In addition, CT-1 enhances glucose-stimulated insulin secretion in MIN6B1 cells and this was repressed by inhibitors of phospholipase C. Furthermore, Ct1 (-/-) mice were more prone to develop diabetes, and their glucose tolerance test showed impaired plasma glucose clearance which correlated with decreased pancreatic insulin secretion. CONCLUSIONS/INTERPRETATION: The results obtained from both in vitro and in vivo experiments show that CT-1 improves beta cell function and survival, and protects mice against STZ-induced diabetes.

[New therapeutic strategies for type 1 diabetes mellitus]. / Nuevas estrategias terapéuticas en diabetes mellitus tipo 1.

The main determinant of the risk of complications from type 1 diabetes mellitus is the total lifetime blood glucose levels. To impact on the health and quality of life of individuals with diabetes, safe and effective methods of achieving and maintaining normoglycemia are needed. Unfortunately, intensive insulin therapy does not achieve normal levels of blood glucose, is difficult to implement for many patients, and limited by the accompanying increased frequency of severe hypoglycemia. Hence, the only way at present to restore permanently normoglycemia without hypoglycemia is to provide the patient with additional beta-cells. This can be achieved by transplanting an intact pancreas, or by transplanting islets. The shortage of functional beta-cells from available donors is one of the major limiting factors for the treatment of diabetes by islet transplantation. Therefore, methods to preserve or even promote regeneration of the beta-cell mass are dearly needed. Significant progress has been made over the last decade in stem cell biology. However, the quest for identification of stem cells has been hampered by the lack of appropriate research tools including assays that allow assess their differentiation potential in vitro and in vivo. Therefore, new techniques are necessary in order to develop new therapeutic strategies based on stem cells for the treatment of diabetes mellitus type 1.