Intranasal Insulin Reduces Body Fat in Men but not in Women

  1. Manfred Hallschmid1,
  2. Christian Benedict1,
  3. Bernd Schultes2,
  4. Horst-Lorenz Fehm2,
  5. Jan Born1 and
  6. Werner Kern2
  1. 1Institute of Neuroendocrinology, University of Lübeck, Lübeck, Germany
  2. 2Department of Internal Medicine I, University of Lübeck, Lübeck, Germany
  1. Address correspondence and reprint requests to Manfred Hallschmid, PhD, Institute of Neuroendocrinology, University of Lübeck, Ratzeburger Allee 160, Haus 23a, 23538 Lübeck, Germany. E-mail: hallschmid{at}kfg.mu-luebeck.de

Abstract

Insulin acts in the central nervous system to reduce food intake and body weight and is considered a major adiposity signal. After intranasal administration, insulin enters the cerebrospinal fluid compartment and alters brain functions in the absence of substantial absorption into the blood stream. Here we report the effects of 8 weeks of intranasal administration of insulin (4 × 40 IU/day) or placebo to two groups of healthy human subjects (12 men and 8 women in each group). The insulin-treated men lost 1.28 kg body wt and 1.38 kg of body fat, and their waist circumference decreased by 1.63 cm. Plasma leptin levels dropped by an average of 27%. In contrast, the insulin-treated women did not lose body fat and gained 1.04 kg body wt due to a rise in extracellular water. Our results provide a strong, first confirmation in humans that insulin acts as a negative feedback signal in the regulation of adiposity and point to a differential sensitivity to the catabolic effects of insulin based on sex.

Footnotes

    • Accepted August 6, 2004.
    • Received June 16, 2004.
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