Reduction of postprandial hyperglycemia in patients with type 2 diabetes reduces NF-kappaB activation in PBMCs.
OBJECTIVE
Short-lasting hyperglycemia results in activation of the transcription factor NF-kappaB in peripheral blood mononuclear cells. We therefore studied whether the postprandial increase in glucose is sufficient to induce mononuclear NF-kappaB activation and whether blunting postprandial hyperglycemia with the alpha-glucosidase inhibitor acarbose reduces NF-kappaB activation.


METHODS
20 patients with type 2 diabetes were included in a double-blind randomized trial receiving 100 mg acarbose or placebo three times a day over a period of eight weeks. Peripheral blood mononuclear cells were isolated before and 120 minutes after a standardized breakfast. NF-kappaB binding activity was estimated by electrophoretic mobility shift assay and NF-kappaB-p65; translocation was determined by Western blot.


RESULTS
Eight weeks of treatment with acarbose significantly reduced postprandial hyperglycemia (p = 0.004 when compared to placebo), postprandial mononuclear NF-kappaB-binding activity (p = 0.045) and nuclear translocation of NF-kappaB-p65 (p = 0.02).


CONCLUSIONS
Reduction of postprandial glucose peak levels by acarbose reduces postprandial mononuclear NF-kappaB activation.
Rudofsky
G
G
Department of Medicine I, University of Heidelberg, Germany.
Reismann
P
P
Schiekofer
S
S
Petrov
D
D
von Eynatten
M
M
Humpert
P M
PM
Isermann
B
B
Müller-Hoff
C
C
Thai
T-P
TP
Lichtenstein
S
S
Bärtsch
U
U
Hamann
A
A
Nawroth
P
P
Bierhaus
A
A
D020909:Acarbose / Q000008:administration & dosage / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001692:Biological Transport / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D006943:Hyperglycemia / Q000097:blood* / Q000209:etiology* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D016328:NF-kappa B / Q000097:blood* / Q000187:drug effects / Q000378:metabolism; D019518:Postprandial Period; D051996:Transcription Factor RelA
D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D016328:NF-kappa B; D051996:Transcription Factor RelA; D020909:Acarbose