If you have any questions about the Leisure League, please email firstname.lastname@example.org. In order to further characterize the influence of the effect of PICK1 on metabolism, we conducted oral glucose tolerance tests (OGTTs). In response to glucose exposure, we observed a significant decrease in plasma blood glucose clearance (Figure 3A) and, therefore, a decrease in insulin secretion in PICK1 mice (Figure 3B). These results indicate that not only GH secretion, but also insulin secretion can be impaired in the absence of PICK1. Glucose intolerance was not due to insulin resistance frequently observed in obese animal models of T2D. On the contrary, an insulin tolerance test (TTI) showed increased insulin sensitivity in PICK1 mice, as illustrated by a significant reduction in CSA (sub-curve) (Figure 3C). Consistent with increased insulin sensitivity, we observed an increase in insulin receptor expression in the liver (Figure 3D). It is interesting to note that an increase in insulin sensitivity has previously been observed in animal models characterized by a limited GH effect . Finally, we found a decrease in plasma triglycerides (Figure 3E) as described in other rodent models of GH deficiency . Together, our data indicate that the metabolic phenotype of PICK1 mice is largely characterized by GH deficiency. In addition, the results suggest an alteration of insulin secretion in accordance with the work of Xia and her colleagues . Finally, we examined whether, with ICA69, PICK1 could play a general role in the formation of secretal vescicules. Previously, chromogranine A (CgA) expression in non-endocrine cells has been shown to lead to the formation of dense nucleus-like granules in non-endocrine cells, consistent with the functional importance of chromogranine in the formation of secretoid vesicles .] If, as suggested by our data, PICK1 with ICA69 function to facilitate the formation of secret vesicles, we assumed that co-expression of PICK1 and ICA69 with CgA should promote the formation of positive CgA vesicles in non-endocrine cells.
First, we codified PICK1 with PCP (PCP-PICK1) and A-ICA69, alone or together, in COS7 cells. Only the GFP-PICK1 and HA-ICA69 immune signals were distributed relatively uniformly in the cytoplasm and showed low coloration with the Giant Golgi Marker (Figure 10A). However, the immune signals GFP-PICK1 and HA-ICA69 clustered around the nucleus and showed a clear overlap with the Giantin immune signal (Figure 10A). When expressed only in COS7 cells, CgA with GFP (CgA-GFP) is mainly in a juxtaposed Golgi-type compartment with little location to punctuate structures in the cytoplasm (Figure 10B), a location confirmed by co-colossal coloration (unpublished data). However, when gfP-PICK1 and HA-ICA69 were expressed at the same time as the CgA PCP, we saw a remarkable redistribution of CgA PCP. Now, PCP CgA has been located to a much higher degree to puncture structures in the cytoplasm that may represent vesicles containing CgA (Figure 10B).