Central resistance to the inhibitory effects of leptin on stimulated insulin secretion with aging.
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 microg/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.
Muzumdar
Radhika H
RH
Division of Pediatric Endocrinology, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Ma
Xiaohui
X
Yang
Xiaoman
X
Atzmon
Gil
G
Barzilai
Nir
N
D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D015309:Glucose Clamp Technique / Q000379:methods; D007275:Injections, Intravenous / Q000379:methods; D007276:Injections, Intraventricular / Q000379:methods; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D020738:Leptin / Q000008:administration & dosage*; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D007328:Insulin; D020738:Leptin