Over the past decade most components in the insulin signalling pathway have been identified in murine and human pancreatic b cells. Insulin signalling has been reported to positively regulate many effects in b cells such as insulin gene expression, insulin secretion, proinsulin byosinthesis and cell cycle progression ; the same effects are regulated by glucose. Even the modulation of tribble 3, a cytoplasmic inhibitor of Akt kinase, altered susceptibility to high glucose and ER stress induced apoptosis in INS-1 cells, streghtening the relevance of Akt regulation in b cell mass and function response. thyroid hormones are widely known for their ability to influence various cellular processes such as mitogenesis and differentiation, which are both considered good candidate targets for counteracting the insorgence of diabetes. We have previously demonstrated that the thyroid hormone T3 stimulates pancreatic ductal cells, considered as b cells precursor, towards a b cell-like phenotype. In addition, we showed that T3 acts as a mitogenic, pro-survival factor in pancreatic b cells, and that it can directly activate Akt; taken together, these results demonstrated that T3 can activate cellular processes strictly related to b cell function such as cell proliferation and survival, cell size regulation, protein synthesis and insulin production. Moreover, our recent study demonstrated that T3 can be a survival factor even for cultured rat islets, counteracting both physiological and pharmacological b cell death. Even in this case T3 can also act as a mitogenic factor. These data strongly sustain our hypothesis that the thyroid hormone T3 can be considered a promoting factor for b cell function, and outline its possible role in contrasting the onset of diabetes. Based on these data, in this study we intended to verify Temozolomide whether T3 is able to preserve and protect functional b cell mass in STZ diabetic animals. Finally, we assayed serum insulin levels to analyze the effect of T3 treatment on islets function. As shown in Figure 7, STZ treatment induced a significant decrease in the insulin response, as showed by the lower levels of serum insulin at the different time Y-27632 dihydrochloride points, according to the affected ability of control glucose blood levels; on the other hand when T3 was administered at the same time of STZ, serum insulin levels were comparable to the control, suggesting that T3 treatment preserves insulin production, preventing STZ effects. These final observations supported the hypothesis on that T3 acts as an antidiabetic in vivo, preserving b cell mass, counteracting b cell apoptosis and regulating the insulin response, via the Akt signalling. To better characterize the physiology of our mice, we decided to exclude the occurence of Insulin intolerance by an Insulin Tolerance test. As shown in the histogram in Figure 7C, all animals showed an adequate Insulin responsive, although, as expected, glucose blood levels were higher in the animals treated with STZ.