Increased postprandial GIP and glucagon responses, but unaltered GLP-1 response after intervention with steroid hormone, relative physical inactivity, and high-calorie diet in healthy subjects.
OBJECTIVE
Increased postprandial glucose-dependent insulinotropic polypeptide (GIP) and glucagon responses and reduced postprandial glucagon-like peptide-1 (GLP-1) responses have been observed in some patients with type 2 diabetes mellitus. The causality of these pathophysiological traits is unknown. We aimed to determine the impact of insulin resistance and reduced glucose tolerance on postprandial GIP, GLP-1, and glucagon responses in healthy subjects.


METHODS
A 4-h 2200 KJ-liquid meal test was performed in 10 healthy Caucasian males without family history of diabetes [age, 24 ± 3 yr (mean ± sd); body mass index, 24 ± 2 kg/m(2); fasting plasma glucose, 4.9 ± 0.3 mm; hemoglobin A(1)c, 5.4 ± 0.1%] before and after intervention using high-calorie diet, relative physical inactivity, and administration of prednisolone (37.5 mg/d) for 12 d.


RESULTS
The intervention resulted in insulin resistance according to the homeostatic model assessment [1.1 ± 0.3 vs. 2.3 (mean ± SEM) ± 1.3; P = 0.02] and increased postprandial glucose excursions [area under curve (AUC), 51 ± 28 vs. 161 ± 32 mm · 4 h; P = 0.045], fasting plasma insulin (36 ± 3 vs. 61 ± 6 pm; P = 0.02), and postprandial insulin responses (AUC, 22 ± 6 vs. 43 ± 13 nm · 4 h; P = 0.03). This disruption of glucose homeostasis had no impact on postprandial GLP-1 responses (AUC, 1.5 ± 0.7 vs. 2.0 ± 0.5 nm · 4 h; P = 0.56), but resulted in exaggerated postprandial GIP (6.2 ± 1.0 vs. 10.0 ± 1.3 nm · 4 h; P = 0.003) and glucagon responses (1.6 ± 1.5 vs. 2.4 ± 3.2; P = 0.007).


CONCLUSIONS
These data suggest that increased postprandial GIP and glucagon responses may occur as a consequence of insulin resistance and/or reduced glucose tolerance. Our data suggest that acute disruption of glucose homeostasis does not result in reduced postprandial GLP-1 responses as observed in some individuals with type 2 diabetes mellitus.
Department of Clinical Physiology, Glostrup Hospital, University of Copenhagen, Nordre Ringvej 57, DK-2600 Glostrup, Denmark. kbaggehansen@dadlnet.dk
Katrine B
KB
Hansen
Tina
T
Vilsbøll
Jonatan I
JI
Bagger
Jens J
JJ
Holst
Filip K
FK
Knop
D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D004032:Diet; D002149:Energy Intake / Q000502:physiology*; D005215:Fasting / Q000378:metabolism; D005749:Gastric Inhibitory Polypeptide / Q000097:blood*; D005934:Glucagon / Q000097:blood*; D052216:Glucagon-Like Peptide 1 / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000502:physiology*; D019518:Postprandial Period / Q000502:physiology*; D011239:Prednisolone / Q000494:pharmacology*; D055815:Young Adult
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D011239:Prednisolone