Diabetes increases the expression of hypothalamic neuropeptides in a spontaneous model of type I diabetes, the nonobese diabetic (NOD) mouse.

1. Synthesis of oxytocin (OT) and arginine-vasopressin (AVP) is increased in induced models of Type I diabetes, such as the streptozotocin model. However, these parameters have not yet been evaluated in spontaneous models, such as the nonobese diabetic mouse (NOD). Therefore, we studied in the magnocellular cells of the paraventricular nucleus (PVN) of nondiabetic and diabetic 16-week-old female NOD mice and control C57B1/6 mice, the immunocytochemistry of OT and AVP peptides and their mRNA expression, using nonisotopic in situ hybridization (ISH). 2. In nondiabetic and diabetic NOD female mice, the number of OT- and AVP-immunoreactive cells were similar to those of the controls, whereas immunoreaction intensity was significantly higher for both peptides in diabetic NOD as compared with nondiabetic NOD and control C57B1/6 mice. 3. ISH analysis showed that the number of OT mRNA-containing cells was in the same range in the three groups, whereas higher number of AVP mRNA expressing cells was found in diabetic NOD mice. However, the intensity of hybridization signal was also higher for both OT and AVP mRNA in the diabetic group as compared with nondiabetic NOD and control mice. 4. Blood chemistry demonstrated that haematrocrit, total plasma proteins, urea, sodium, and potassium were within normal limits in diabetic mice. Thus, NOD mice were neither hypernatremic nor dehydrated. 5. We suggest that upregulation of OT and AVP reflects a high-stress condition in the NOD mice. Diabetes may affect neuropeptide-producing cells of the PVN, with the increased AVP and OT playing a deleterious role on the outcome of the disease.