Artikel
Genexpression of Nitric Oxide Synthase Isoforms in the HPA Axis of STZ-Induced Diabetic Rats
Genexpression der Stickstoffmonoxid-Synthasen in der HPA-Achse der STZ-induzierten Diabetesratten
Suche in Medline nach
Autoren
Veröffentlicht: | 11. November 2004 |
---|
Gliederung
Text
Nitric oxide (NO) modulates the activity of hypothalamo-pituitary-adrenal (HPA) axis of streptozotocin-induced diabetic (STZ-D) rodents which show human type-1 like diabetes. Recent data showed that treatment of STZ-D rats with NO-synthase (NOS) inhibitors reduced hyperglycemia and improved diabetic state. To further evaluate the role of NO in the HPA axis we measured the mRNA and protein levels of neuronal (n), endothelial (e) and inducible (i) NOS in the HPA axis of STZ-D rats using RT-PCR and Western blot techniques, respectively, and compared with non-diabetic controls. In addition, we also determined the amounts of ACTH, corticosterone and aldosterone in the plasma of STZ-D rats.
Diabetes was confirmed by plasma insulin, glucose and leptin levels. STZ-D rats showed elevated plasma corticosterone and aldosterone levels, whereas plasma ACTH levels were not changed. Hypothalamic and adrenal nNOS mRNA and protein levels were elevated in the STZ-D rats whereas adrenal iNOS mRNA and protein levels were attenuated. No change in the eNOS expression of HPA axis was observed. Treatment of STZ-D rats with insulin reversed not only hyperglycemia, hypoinsulinemia and hypoleptinemia but also the increased plasma corticosterone and aldosterone levels to control levels. Furthermore, the increased hypothalamic and adrenal nNOS expression was reversed to control levels by insulin treatment. However, the STZ-induced reduction in the adrenal iNOS expression was not reversed by insulin treatment.
Our data suggest that upregulation of hypothalamic and adrenal nNOS mRNA and protein expression may be associated with many of the physiological changes in the diabetic state. However, the role of adrenal iNOS expression in diabetes has to be clarified.