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Evidence for Insulin Resistance of Protein Breakdown

Per-Olof Hasselgren, MD, PhD; Brad W. Warner, MD; J. Howard James; Hiroo Takehara, MD; Josef E. Fischer, MD

Arch Surg. 1987;122(2):228-233.

Abstract
• We investigated the effect of different concentrations of insulin (0, 10, 1x10², 1x10³, 1x10⁴, and 1x10⁵ mU/L [0, 70, 7x10², 7x10³, 7x10⁴, and 7x10⁵ pmol/L]) on amino acid (-aminoisobutyric acid) uptake and protein synthesis and breakdown in incubated extensor digitorum longus (EDL) and soleus muscles of rats. We studied three groups: (1) untreated, fed rats; (2) sham-operated rats; and (3) septic rats. Sepsis was induced by cecal ligation and puncture. The -aminoisobutyric acid uptake was increased by insulin in all three groups. Protein synthesis was maximally stimulated by 30% to 40% by 1x10² mU/L (7x10² pmol/L) of insulin in all three groups. Protein degradation in soleus muscle was not affected by insulin. In EDL muscles from untreated and sham-operated rats, protein breakdown was reduced by 15% to 20% by 1 x 10² mU/L (7x10² pmol/L) of insulin. In contrast, protein breakdown was not inhibited by insulin in septic EDL muscle until the concentration of the hormone was increased to 1 x10⁴ mU/L (7x10⁴ pmol/L), at which concentration the hormonal effect was less than half that in nonseptic muscle. The results suggest a postreceptor insulin resistance of protein breakdown in septic muscle, while the response to the hormone of amino acid transport and protein synthesis was not altered in sepsis.

(Arch Surg 1987;122:228-233)

Author Affiliations
From the Department of Surgery, University of Cincinnati Medical Center.

Footnotes
Accepted for publication Oct 9, 1986.

Read before the Sixth Annual Meeting of the Surgical Infection Society, Chicago, April 22, 1986.

Reprint requests to Department of Surgery, University of Cincinnati Medical Center, 231 Bethesda Ave (ML #558), Cincinnati, OH 45267 (Dr Fischer).

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