Fe. Saravia et al., Diabetes increases the expression of hypothalamic neuropeptides in a spontaneous model of type I diabetes, the nonobese diabetic (NOD) mouse, CELL MOL N, 21(1), 2001, pp. 15-27
1. Synthesis of oxytocin (OT) and arginine-vasopressin (AVP) is increased i
n induced models of Type I diabetes, such as the streptozotocin model. Howe
ver, these parameters have not yet been evaluated in spontaneous models, su
ch as the nonobese diabetic mouse (NOD). Therefore, we studied in the magno
cellular cells of the paraventricular nucleus (PVN) of nondiabetic and diab
etic 16-week-old female NOD mice and control C57B1/6 mice, the immunocytoch
emistry 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-i
mmunoreactive cells were similar to those of the controls, whereas immunore
action 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 t
he same range in the three groups, whereas higher number of AVP mRNA expres
sing cells was found in diabetic NOD mice. However, the intensity of hybrid
ization signal was also higher for both OT and AVP mRNA in the diabetic gro
up as compared with nondiabetic NOD and control mice.
4. Blood chemistry demonstrated that haematrocrit, total plasma proteins, u
rea, 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 condit
ion in the NOD mice. Diabetes may affect neuropeptide-producing cells of th
e PVN, with the increased AVP and OT playing a deleterious role on the outc
ome of the disease.