Pancreatic B-cell function is altered by oxidative stress induced by acute hyperglycaemia.
OBJECTIVE
Type 2 diabetes is preceded by a symptom-free period of impaired glucose tolerance (IGT). Pancreatic B-cell function decreases as glucose intolerance develops. In many patients with IGT, fasting blood glucose is within normal limits and hyperglycaemia occurs only postprandially. We examined whether pancreatic B-cell function changes during acute hyperglycaemia induced by oral glucose loading.


METHODS
We calculated the insulinogenic index (I.I.) as an indicator of pancreatic B-cell function and measured serum levels of thioredoxin, a marker of cellular redox state, and 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative stress, during a 75-g oral glucose tolerance test (OGTT) in 45 subjects [24 patients with normal glucose tolerance (NGT), 14 with IGT and seven with Type 2 diabetes].


RESULTS
Thioredoxin levels decreased after glucose loading [66.1 +/- 23.7, *59.3 +/- 22.4, *49.3 +/- 21.2 and *37.7 +/- 18.0 ng/ml, fasting (0 min) and at 30, 60 and 120 min, respectively; *P < 0.001 vs. fasting]. In contrast, concentrations of 8-OHdG peaked at 30 min and then gradually decreased (0.402 +/- 0.123, *0.440 +/- 0.120, 0.362 +/- 0.119 and 0.355 +/- 0.131 ng/ml, *P < 0.05 vs. fasting, P < 0.01 vs. 30 min). The insulinogenic index correlated with the change in thioredoxin levels (r = 0.34, P < 0.05). However, there was no relationship with the change in 8-OHdG levels from 0 to 30 min.


CONCLUSIONS
Hyperglycaemia in response to oral glucose impairs pancreatic B-cell function with decreasing thioredoxin levels. The augmented oxidative stress induced by hyperglycaemia may affect the cellular redox state. These findings strongly suggest that repeated postprandial hyperglycaemia may play an important role in the development and progression of diabetes mellitus.
Miyazaki
Y
Y
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Honjo, Kumamoto City, Japan.
Kawano
H
H
Yoshida
T
T
Miyamoto
S
S
Hokamaki
J
J
Nagayoshi
Y
Y
Yamabe
H
H
Nakamura
H
H
Yodoi
J
J
Ogawa
H
H
D000284:Administration, Oral; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000150:complications*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D013879:Thioredoxins / Q000378:metabolism
D007004:Hypoglycemic Agents; D013879:Thioredoxins; D005947:Glucose