title: Effect of oral amino acids on counterregulatory responses and cognitive function during insulin-induced hypoglycemia in nondiabetic and type 1 diabetic people.
abstract: 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.
  
  
  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. Beta-OH-butyrate was less suppressed after amino acids (200 +/- 15 vs. 93 +/- 9 micromol/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.
authors.affiliation: Department of Internal Medicine, University of Perugia, Perugia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Rossetti
authors.forename: Francesca
authors.initials: F
authors.lastname: Porcellati
authors.forename: Natalia
authors.initials: N
authors.lastname: Busciantella Ricci
authors.forename: Paola
authors.initials: P
authors.lastname: Candeloro
authors.forename: Patrizia
authors.initials: P
authors.lastname: Cioli
authors.forename: K Sreekumaran
authors.initials: KS
authors.lastname: Nair
authors.forename: Fausto
authors.initials: F
authors.lastname: Santeusanio
authors.forename: Geremia B
authors.initials: GB
authors.lastname: Bolli
authors.forename: Carmine G
authors.initials: CG
authors.lastname: Fanelli
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000596:Amino Acids / Q000008:administration & dosage / Q000494:pharmacology*; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003071:Cognition / Q000187:drug effects*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000503:physiopathology*; D004837:Epinephrine / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D015309:Glucose Clamp Technique; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007003:Hypoglycemia / Q000139:chemically induced* / Q000523:psychology*; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D007328:Insulin / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010191:Pancreatic Polypeptide / Q000097:blood; D012016:Reference Values; D011795:Surveys and Questionnaires; D014145:Trail Making Test
chemical_list: D000596:Amino Acids; D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D010191:Pancreatic Polypeptide; D005934:Glucagon; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine