Amino acid ingestion strongly enhances insulin secretion in patients with long-term type 2 diabetes

Diabetes Care. 2003 Mar;26(3):625-30. doi: 10.2337/diacare.26.3.625.


Objective: Insulin secretion in response to carbohydrate intake is blunted in type 2 diabetic patients. However, it is not clear whether the insulin response to other stimuli, such as amino acids, is also diminished. Recently, we defined an optimal insulinoptropic mixture containing free leucine, phenylalanine, and a protein hydrolysate that substantially enhances the insulin response in healthy young subjects when coingested with carbohydrate. In this study, we aimed to investigate the insulinotropic capacity of this mixture in long-term type 2 diabetic patients.

Research design and methods: Ten type 2 diabetic patients (aged 59.1 +/- 2.0 years, BMI 26.5 +/- 0.7 kg/m(2)) and 10 healthy control subjects (58.8 +/- 2.1 years, 26.5 +/- 0.7 kg/m(2)) visited our lab twice, during which insulin responses were determined following ingestion of carbohydrate only (CHO) or carbohydrate with the free amino acid/protein mixture (CHO+PRO). All subjects received 0.7 g x kg(-1) x h(-1) carbohydrate with or without 0.35 g x kg(-1) x h(-1) of the amino acid/protein mixture.

Results: Insulin responses were dramatically increased in the CHO+PRO trial in both the type 2 diabetic and control groups (189 and 114%, respectively) compared with the CHO trial (P < 0.01). Plasma glucose, glucagon, growth hormone, cortisol, IGF-I, and IGF binding protein 3 responses were not different between trials within the 2-h time frame.

Conclusions: The insulin secretory capacity in long-term type 2 diabetic patients is substantially underestimated, as the insulin response following carbohydrate intake can be nearly tripled by coingestion of a free amino acid/protein mixture. Future research should be performed to investigate whether such nutritional interventions can improve postprandial glucose disposal.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial

MeSH terms

  • Amino Acids / administration & dosage*
  • Blood Glucose / drug effects
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Dietary Carbohydrates / administration & dosage
  • Humans
  • Insulin / blood
  • Insulin / metabolism*
  • Insulin Secretion
  • Leucine / administration & dosage
  • Male
  • Middle Aged
  • Phenylalanine / administration & dosage
  • Protein Hydrolysates / administration & dosage


  • Amino Acids
  • Blood Glucose
  • Dietary Carbohydrates
  • Insulin
  • Protein Hydrolysates
  • Phenylalanine
  • Leucine