Leptin increases circulating glucose, insulin and glucagon via sympathetic neural activation in fasted mice

B. Ahrén, Peter J Havel

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

OBJECTIVE: A number of recent studies suggest that leptin has effects on glucose metabolism and pancreatic hormone secretion. Therefore, the effect of leptin administration on circulating glucose, insulin and glucagon in fed and fasted mice was investigated. The potential contribution of the sympathetic nervous system to the effects of leptin was also examined. DESIGN: Recombinant human or murine leptin was administered intraperitoneally (300 μg/mouse per 12 h over 24 h) to fed or fasted, normal or chemically sympathectomized NMRI mice. Blood samples were collected at baseline and after 24 h. MEASUREMENTS: Plasma concentrations of glucose, insulin and glucagon. RESULTS: In the fed state (n = 24), leptin administration did not affect glucose, insulin or glucagon concentrations after 24 h. Fasting (n = 24) reduced body weight by 2.2 ± 0.4 g, plasma glucose by 3.7 ± 0.4 mmol/l, plasma insulin by 138 ± 35 pmol/l, and plasma glucagon by 32 ± 7 pg/ml. In fasted mice, human leptin (n = 24) increased plasma glucose by 1.5 ± 0.2 mmol/l (P = 0.041), plasma insulin by 95 ± 22 pmol/l (P = 0.018), and plasma glucagon by 16 ± 3 pg/ml (P = 0.025), relative to saline-injected control animals. Murine leptin exerted similar stimulating effects on circulating glucose (+1.0 ± 0.2 mmol/l, P = 0.046), insulin (+58 ± 17 pmol/l, P = 0.038) and glucagon (+24 ± 9 pg/ml, P = 0.018) as human leptin in fasted mice (n = 12) with no significant effect in fed mice (n = 12). Human leptin did not affect circulating glucose, insulin or glucagon in fasted mice after chemical sympathectomy with 6-hydroxydopamine (40 mg/kg iv 48 h prior to fasting; n = 12). CONCLUSION: Leptin increases circulating glucose, insulin and glucagon in 24 h fasted mice by a mechanism requiring intact sympathetic nerves.

Original languageEnglish (US)
Pages (from-to)660-665
Number of pages6
JournalInternational Journal of Obesity
Volume23
Issue number6
StatePublished - 1999

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Keywords

  • Glucagon secretion
  • Glucose
  • Insulin secretion
  • Leptin
  • Mice
  • NMRI

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Public Health, Environmental and Occupational Health
  • Endocrinology
  • Food Science
  • Endocrinology, Diabetes and Metabolism

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