Effect of Oral Amino Acids on Counterregulatory Responses and Cognitive Function During Insulin-Induced Hypoglycemia in Nondiabetic and Type 1 Diabetic People

  1. Paolo Rossetti1,
  2. Francesca Porcellati1,
  3. Natalia Busciantella Ricci1,
  4. Paola Candeloro1,
  5. Patrizia Cioli1,
  6. K. Sreekumaran Nair2,
  7. Fausto Santeusanio1,
  8. Geremia B. Bolli1 and
  9. Carmine G. Fanelli1
  1. 1Department of Internal Medicine, University of Perugia, Perugia, Italy
  2. 2Division of Endocrinology, Mayo Clinic, Rochester, Minnesota
  1. Corresponding author: Prof. Geremia B. Bolli, gbolli{at}


OBJECTIVE—Amino acids stimulate glucagon responses to hypoglycemia and may be utilized by the brain. The aim of this study was to assess the responses to hypoglycemia in nondiabetic and type 1 diabetic subjects after ingestion of an amino acid mixture.

RESEARCH DESIGN AND METHODS—Ten nondiabetic and 10 diabetic type 1 subjects were studied on three different occasions during intravenous insulin (2 mU · kg−1 · min−1) plus variable glucose for 160 min. In two studies, clamped hypoglycemia (47 mg/dl plasma glucose for 40 min) was induced and either oral placebo or an amino acid mixture (42 g) was given at 30 min. In the third study, amino acids were given, but euglycemia was maintained.

RESULTS—Plasma glucose and insulin were no different in the hypoglycemia studies with both placebo and amino acids (P > 0.2). After the amino acid mixture, plasma amino acid concentrations increased to levels observed after a mixed meal (2.4 ± 0.13 vs. placebo study 1.7 ± 0.1 mmol/l, P = 0.02). During clamped euglycemia, ingestion of amino acids resulted in transient increases in glucagon concentrations, which returned to basal by the end of the study. During clamped hypoglycemia, glucagon response was sustained and increased more in amino acid studies versus placebo in nondiabetic and diabetic subjects (P < 0.05), but other counter-regulatory hormones and total symptom score were not different. β-OH-butyrate was less suppressed after amino acids (200 ± 15 vs. 93 ± 9 μmol/l, P = 0.01). Among the cognitive tests administered, the following indicated less deterioration after amino acids than placebo: Trail-Making part B, PASAT (Paced Auditory Serial Addition Test) (2 s), digit span forward, Stroop colored words, and verbal memory tests for nondiabetic subjects; and Trail-Making part B, digit span backward, and Stroop color tests for diabetic subjects.

CONCLUSIONS—Oral amino acids improve cognitive function in response to hypoglycemia and enhance the response of glucagon in nondiabetic and diabetic subjects.


  • Published ahead of print at on 4 April 2008.

    Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See for details.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted March 28, 2008.
    • Received February 26, 2008.
| Table of Contents