Insulin and nateglinide reduce monocyte adhesion to endothelial cells in Goto-Kakizaki rats exhibiting repetitive blood glucose fluctuation.

Abstract

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.

• Authors: Atsuko Tanaka, Kosuke Azuma, Yukiko Toyofuku, Atsuko Kurokawa, Aiko Otsuka, Tomoya Mita, Takahisa Hirosea, Yoshio Fujitani, Katsumi Miyauchi, Hiroyuki Daida, Ryuzo Kawamori, Hirotaka Watada
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 350 Issue 1 Pg. 195-201 (Nov 10 2006) ISSN: 0006-291X [Print] United States
• PMID: 16997277 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Cyclohexanes
• Insulin
• RNA, Messenger
• Vascular Cell Adhesion Molecule-1
• Intercellular Adhesion Molecule-1
• Nateglinide
• Phenylalanine

Topics

• Animals
• Aorta (drug effects)
• Blood Glucose (metabolism)
• Body Weight (drug effects)
• Cell Adhesion (drug effects)
• Cyclohexanes (pharmacology)
• Endothelial Cells (cytology, drug effects)
• Gene Expression Regulation
• Insulin (pharmacology)
• Intercellular Adhesion Molecule-1 (genetics)
• Male
• Monocytes (cytology, drug effects)
• Nateglinide
• Phenylalanine (analogs & derivatives, pharmacology)
• RNA, Messenger (genetics)
• Rats
• Vascular Cell Adhesion Molecule-1 (genetics)