| Autor: |
Akirav EM; Department of Physiology, University of Toronto, Ontraio, Canada., Chan O, Inouye K, Riddell MC, Matthews SG, Vranic M |
| Jazyk: |
angličtina |
| Zdroj: |
Metabolism: clinical and experimental [Metabolism] 2004 Dec; Vol. 53 (12), pp. 1558-64. |
| DOI: |
10.1016/j.metabol.2004.06.024 |
| Abstrakt: |
Chronic leptin administration at pharmacologic doses normalizes food intake and body weight in streptozotocin (STZ)-diabetic rats. We examined the metabolic effects of acute partial physiological leptin restoration in STZ-diabetic rats by using subcutaneous osmotic mini pumps. Groups: (1) Rats infused with vehicle (DV); (2) rats infused with recombinant murine methionine leptin (DL) at 4.5 microg . (kg body weight . d)(-1); (3)pair-fed rats (DP) given a food ration matching that consumed by the DL group. A fourth group of nondiabetic, normal (N) rats was also studied to assess normal metabolic efficiency, hypothalamic-pituitary-adrenal (HPA) activity and sympathoadrenal activity. Following leptin infusion, food consumption by DL rats was significantly lower than in DV rats. Paradoxically, despite a similar food intake to that of the DP group, which demonstrated a 40% reduction in body mass, DL rats increased their initial body weight by approximately 20% (P < .05). Plasma corticosterone and ACTH concentrations were elevated by 2-fold to 3-fold in DL versus N, DP, and DV rats. In the pars distalis, glucocorticoid receptor (GR) mRNA levels were significantly higher in DL and DP rats compared with N and DV rats. Our results suggest that partial restoration of physiologic leptin: (1) successfully reduces hyperphagia while allowing body weight gain in STZ-diabetic rats; (2) increases corticosterone levels in STZ-diabetic rats, which may in turn counteract the anorexic effects of diabetes; and (3) is associated with increased pituitary GR mRNA levels, despite elevated corticosterone levels, suggesting that leptin may interfere with the negative feedback regulation of the HPA axis. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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