Insulin and nateglinide reduce monocyte adhesion to endothelial cells in Goto-Kakizaki rats exhibiting repetitive blood glucose fluctuation.
Epidemiological studies demonstrated the importance of postprandial hyperglycemia on the progression of atherosclerosis. However, whether treatment of postprandial hyperglycemia by insulin or insulin secretagogues has a beneficial effect on atherosclerosis has not been elucidated. To elucidate the effects of reduction of postprandial rise of blood glucose by insulin and nateglinide on monocyte adhesion to endothelial cells, we used non-obese type 2 diabetic Goto-Kakizaki (GK) rats fed twice daily, as a model of repetitive postprandial hyperglycemia. We investigated the effects of insulin injection and nateglinide administration just before each meal for 12 weeks on monocyte adhesion to endothelial cells. By setting the doses of insulin and nateglinide, both treatment significantly reduced postprandial hyperglycemia without significant reduction of HbA1c. Nateglinide also reduced serum insulin level just after 1 h meal. Both nateglinide and insulin therapy reduced the number of monocytes adherent to the aortic endothelial layer. Nateglinide, but not insulin, reduced intimal thickness of the thoracic aorta. While increased serum insulin level might be regarded as a factor responsible for the progression of atherosclerosis, our data showed that treatment with pre-meal insulin or nateglinide, which reduces postprandial hyperglycemia, reduced monocyte adhesion to endothelial cells.
Tanaka
Atsuko
A
Department of Medicine, Metabolism and Endocrinology, Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Azuma
Kosuke
K
Toyofuku
Yukiko
Y
Kurokawa
Atsuko
A
Otsuka
Aiko
A
Mita
Tomoya
T
Hirosea
Takahisa
T
Fujitani
Yoshio
Y
Miyauchi
Katsumi
K
Daida
Hiroyuki
H
Kawamori
Ryuzo
R
Watada
Hirotaka
H
D000818:Animals; D001011:Aorta / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D003510:Cyclohexanes / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects*; D005786:Gene Expression Regulation; D007328:Insulin / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D008297:Male; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects*; D000077715:Nateglinide; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics
D001786:Blood Glucose; D003510:Cyclohexanes; D007328:Insulin; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D000077715:Nateglinide; D010649:Phenylalanine