TY - JOUR
T1 - Central resistance to the inhibitory effects of leptin on stimulated insulin secretion with aging
AU - Muzumdar, Radhika H.
AU - Ma, Xiaohui
AU - Yang, Xiaoman
AU - Atzmon, Gil
AU - Barzilai, Nir
N1 - Funding Information:
This work was supported by grants from the National Institutes of Health (RO1-AG 18381 to NB), the American Diabetes Association, and by the Core laboratories of the Albert Einstein Diabetes Research and Training Center (DK 20541).
PY - 2006/9
Y1 - 2006/9
N2 - Aging is associated with resistance to the effects of leptin on food intake and energy homeostasis. We examined if old rats were resistant to the effects of leptin on glucose stimulated insulin secretion. When leptin was infused intravenously (0.5 μg/kg/min) under hyperglycemic clamp conditions (11 mM) in young (n = 5) and old rats (n = 10, 5 ad libitum fed and five with surgical removal of visceral fat), glucose stimulated insulin secretion was significantly decreased by 44% in the young rats, but not in old rats (31.8 ± 2.8 to 17.9 ± 1.0 versus 33.7 ± 1.4 versus 31.0 ± 1.7 and 24.7 ± 1.6 versus 21.0 ± 2.8 in young versus old versus old VF- respectively, p < 0.01). To identify if the resistance to leptin is secondary to impaired transport across the blood brain barrier (BBB), we infused leptin into the third ventricle (intra-cerebro ventricular, ICV). ICV infusion of leptin elicited a partial effect on glucose stimulated insulin secretion in the old (25.7 ± 2.5 to 15.4 ± 2.4 versus 24.4 ± 2.4 to 19.0 ± 2.0 in young versus old, respectively) suggesting that part of the leptin resistance was beyond the BBB. Resistance to the effects of leptin on insulin secretion in aging may protect against the onset of diabetes in old subjects.
AB - Aging is associated with resistance to the effects of leptin on food intake and energy homeostasis. We examined if old rats were resistant to the effects of leptin on glucose stimulated insulin secretion. When leptin was infused intravenously (0.5 μg/kg/min) under hyperglycemic clamp conditions (11 mM) in young (n = 5) and old rats (n = 10, 5 ad libitum fed and five with surgical removal of visceral fat), glucose stimulated insulin secretion was significantly decreased by 44% in the young rats, but not in old rats (31.8 ± 2.8 to 17.9 ± 1.0 versus 33.7 ± 1.4 versus 31.0 ± 1.7 and 24.7 ± 1.6 versus 21.0 ± 2.8 in young versus old versus old VF- respectively, p < 0.01). To identify if the resistance to leptin is secondary to impaired transport across the blood brain barrier (BBB), we infused leptin into the third ventricle (intra-cerebro ventricular, ICV). ICV infusion of leptin elicited a partial effect on glucose stimulated insulin secretion in the old (25.7 ± 2.5 to 15.4 ± 2.4 versus 24.4 ± 2.4 to 19.0 ± 2.0 in young versus old, respectively) suggesting that part of the leptin resistance was beyond the BBB. Resistance to the effects of leptin on insulin secretion in aging may protect against the onset of diabetes in old subjects.
KW - Aging
KW - Leptin and insulin secretion
KW - Leptin resistance
UR - http://www.scopus.com/inward/record.url?scp=33746214687&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33746214687&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2005.07.007
DO - 10.1016/j.neurobiolaging.2005.07.007
M3 - Article
C2 - 16122839
AN - SCOPUS:33746214687
SN - 0197-4580
VL - 27
SP - 1308
EP - 1314
JO - Neurobiology of Aging
JF - Neurobiology of Aging
IS - 9
ER -
