Control of plasma glucose with alpha-glucosidase inhibitor attenuates oxidative stress and slows the progression of heart failure in mice.

Abstract

OBJECTIVE:

It has been suggested that reduction in glucose levels contributes to the prolongation of life span of rodents in conjunction with restricted food intake, and hyperglycemia has been confirmed as a risk factor for cardiovascular disease (CVD), raising the possibility that better glycemic control could slow the progression of CVD. This study was designed to determine whether impaired glucose tolerance develops during the progression of cardiac hypertrophy and heart failure, and whether tight glycemic control could reduce the severity of heart failure.

METHODS:

In male C57BL/6 mice, transverse aortic constriction (TAC) was employed to create cardiac hypertrophy and heart failure. The involvement of NADPH in TAC mice and cardiac myocytes in the neonatal rat was investigated.

RESULTS:

The random-fed plasma glucose concentration was higher in TAC mice, and it was reduced to about 100 mg/dL by voglibose (an alpha-glycosidase inhibitor). Four weeks after TAC, both the heart weight/body weight ratio and the lung weight/body weight ratio were lower in the voglibose group than in the TAC group. Echocardiographic and invasive hemodynamic examination showed improvement of left ventricular function in voglibose-treated mice. Voglibose treatment decreased the myocardial expression of an NADPH oxidase subunit (p47phox). Glucose dose-dependently increased both neonatal rat myocyte protein synthesis and the expression of p47phox protein, while apocynin (an NADPH oxidase inhibitor) blocked the enhancement of protein synthesis by high glucose.

CONCLUSION:

Improvement of glycemic control through voglibose therapy inhibited cardiac remodeling by decreasing myocardial oxidative stress in mice with cardiac pressure overload.

• Authors: Yulin Liao, Seiji Takashima, Hui Zhao, Yoshihiro Asano, Yasunori Shintani, Tetsuo Minamino, Jiyoong Kim, Masashi Fujita, Masatsugu Hori, Masafumi Kitakaze
• Journal: Cardiovascular research (Cardiovasc Res) Vol. 70 Issue 1 Pg. 107-16 (Apr 01 2006) ISSN: 0008-6363 [Print] England
• PMID: 16510136 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acetophenones
• Fatty Acids, Nonesterified
• Glycoside Hydrolase Inhibitors
• Insulin
• Inositol
• acetovanillone
• NADPH Oxidases
• neutrophil cytosolic factor 1
• Glucose
• voglibose

Topics

• Acetophenones (pharmacology)
• Animals
• Blotting, Western (methods)
• Body Weight
• Cells, Cultured
• Disease Progression
• Echocardiography
• Fatty Acids, Nonesterified (blood)
• Glucose (metabolism, pharmacology)
• Glycoside Hydrolase Inhibitors
• Heart Failure (drug therapy, metabolism, pathology)
• Hyperglycemia (drug therapy, metabolism, pathology)
• Inositol (analogs & derivatives, therapeutic use)
• Insulin (blood)
• Lung (pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Models, Animal
• Myocardium (metabolism, pathology)
• Myocytes, Cardiac
• NADPH Oxidases (antagonists & inhibitors, metabolism)
• Organ Size
• Oxidative Stress
• Rats
• Reverse Transcriptase Polymerase Chain Reaction
• Ventricular Dysfunction, Left (drug therapy, metabolism)