Central resistance to the inhibitory effects of leptin on stimulated insulin secretion with aging

Radhika H. Muzumdar, Xiaohui Ma, Xiaoman Yang, Gil Atzmon, Nir Barzilai

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1308-1314
Number of pages7
JournalNeurobiology of Aging
Issue number9
StatePublished - Sep 2006


  • Aging
  • Leptin and insulin secretion
  • Leptin resistance

ASJC Scopus subject areas

  • General Neuroscience
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology


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