Physiological augmentation of amino acid-induced insulin secretion by GIP and GLP-I but not by CCK-8.
It was the aim of this study to test insulinotropic actions of cholecystokinin octapeptide (CCK-8), gastric inhibitory polypeptide (GIP), and glucagon-like peptide I (GLP-I)-(7--36) amide at basal glucose but physiologically elevated amino acid concentrations. Therefore, in nine fasting healthy volunteers, an amino acid mixture was infused intravenously (12.6 g/h over 120 min). On separate occasions, from 30 to 120 min, placebo (0.9% NaCl-1% human serum albumin), synthetic sulfated CCK-8 (0.5 pmol.kg-1.min-1), human GIP (1 pmol.kg-1.min-1), or GLP-I-(7--36) amide (0.3 pmol.kg-1.min-1) was infused intravenously to mimic physiological increments after a meal. The amino acid infusion lead to a small increment in plasma glucose from 4.8 +/- 0.2 to 5.0 +/- 0.2 mmol/l and significantly elevated insulin and C-peptide concentrations. GIP and GLP-I-(7--36) amide further stimulated insulin (1.8-fold, P = 0.0001 and 0.004, respectively) and C-peptide (1.3-fold, P = 0.0003 and 0.013, respectively), with a subsequent slight reduction in plasma glucose (P < 0.0001). Insulin and C-peptide then decreased again in parallel. CCK-8 was without effect on insulin and C-peptide levels. In conclusion, GIP and GLP-I-(7--36) amide are not only able to interact with elevated plasma glucose but are insulinotropic also with physiologically raised amino acid concentrations. Such an interaction could play a role after the ingestion of mixed meals. Cholecystokinin, on the other hand, is not a physiological incretin also under these conditions.
Fieseler
P
P
Department of Medicine, Georg-August University, Göttingen, Germany.
Bridenbaugh
S
S
Nustede
R
R
Martell
J
J
Orskov
C
C
Holst
J J
JJ
Nauck
M A
MA
D000328:Adult; D000596:Amino Acids / Q000494:pharmacology*; D004044:Dietary Proteins / Q000494:pharmacology; D004435:Eating; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology*; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D010179:Pancreas / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology; D012844:Sincalide / Q000494:pharmacology*
D000596:Amino Acids; D004044:Dietary Proteins; D007328:Insulin; D010446:Peptide Fragments; D010455:Peptides; C055453:glucagon-like peptide 1 (7-36)amide; D005749:Gastric Inhibitory Polypeptide; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D012844:Sincalide