GIP receptor antagonism reverses obesity, insulin resistance, and associated metabolic disturbances induced in mice by prolonged consumption of high-fat diet

Sep 13, 2007American journal of physiology. Endocrinology and metabolism

Blocking GIP receptors may reverse obesity, insulin resistance, and related metabolic problems caused by long-term high-fat diet in mice

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Abstract

Daily injection of the GIP receptor antagonist (Pro(3))GIP for 50 days significantly decreased body weight in mice fed a high-fat diet.

  • Administration of (Pro(3))GIP restored plasma glucose, glycated hemoglobin, and pancreatic insulin levels to those of chow-fed mice.
  • Circulating triglyceride and cholesterol levels were significantly reduced following (Pro(3))GIP treatment.
  • Adipose tissue mass and hypertrophy, as well as triglyceride deposition in liver and muscle, were significantly decreased.
  • Improvement in insulin sensitivity, meal tolerance, and normalization of glucose tolerance was observed in treated mice.
  • Circulating levels of glucagon and corticosterone were significantly decreased, while levels of GLP-1, GIP, resistin, and adiponectin remained unchanged.

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