Acarbose, an alpha-glucosidase inhibitor, improves endothelial dysfunction in Goto-Kakizaki rats exhibiting repetitive blood glucose fluctuation.
Several epidemiological studies have revealed that subjects with postprandial hyperglycemia are at increased risk of cardiovascular disease. However, the impact of postprandial hyperglycemia and its treatment on endothelial function has not been clarified yet. In this study, Goto-Kakizaki (GK) rats, a non-obese type 2 diabetes model, fed twice daily were used as a model of repetitive postprandial glucose spikes. We investigated the endothelial function in these rats treated or untreated with acarbose, an alpha-glucosidase inhibitor. Administration of acarbose for 12 weeks markedly improved postprandial hyperglycemia, postprandial insulin level, total cholesterol, triglyceride, and free fatty acid level in GK rats. Furthermore, acarbose efficiently reduced the number of monocytes adherent to aortic endothelial layer, improved acetylcholine-dependent vasodilatation, and reduced intimal thickening of the aorta. While it is generally regarded that repetitive postprandial hyperglycemia is associated with the onset of cardiovascular diseases, our data demonstrated that acarbose treatment efficiently ameliorated endothelial dysfunction and reduced intimal thickening, thus adding support to the protective effect of acarbose against the onset of cardiovascular disease.
Azuma
Kosuke
K
Department of Medicine, Metabolism and Endocrinology, Juntendo University, School of Medicine, Tokyo, Japan.
Toyofuku
Yukiko
Y
Iesaki
Takafumi
T
Otsuka
Aiko
A
Tanaka
Atsuko
A
Mita
Tomoya
T
Hirose
Takahisa
T
Tanaka
Yasushi
Y
Daida
Hiroyuki
H
Kawamori
Ryuzo
R
Watada
Hirotaka
H
D020909:Acarbose / Q000627:therapeutic use*; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000473:pathology; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006943:Hyperglycemia / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D023421:Models, Animal; D019518:Postprandial Period / Q000187:drug effects; D051381:Rats; D013997:Time Factors; D017539:Tunica Intima / Q000473:pathology
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D000109:Acetylcholine; D020909:Acarbose