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Br J Pharmacol. 2007 May;151(2):216-25. Epub 2007 Mar 20.

Increased insulin sensitivity and reduced micro and macro vascular disease induced by 2-deoxy-D-glucose during metabolic syndrome in obese JCR: LA-cp rats.

Author information

1
Metabolic and Cardiovascular Diseases Laboratory, Alberta Institute for Human Nutrition, University of Alberta, Edmonton, Alberta, Canada. Jim.Russell@ualberta.ca

Abstract

BACKGROUND AND PURPOSE:

The metabolic syndrome, characterized by obesity, insulin resistance and dyslipidemia, is a major cause of cardiovascular disease. The origins of the syndrome have been hypothesized to lie in continuous availability of energy dense foods in modern societies. In contrast, human physiology has evolved in an environment of sporadic food supply and frequent food deprivation. Intermittent food restriction in rats has previously been shown to lead to reduction of cardiovascular risk and a greater life span. The non-metabolizable glucose analogue, 2-deoxy-D-glucose (2-DG) is taken up by cells and induces pharmacological inhibition of metabolism of glucose. We hypothesized that intermittent inhibition of glucose metabolism, a metabolic deprivation, may mimic intermittent food deprivation and ameliorate metabolic and pathophysiological aspects of the metabolic syndrome.

EXPERIMENTAL APPROACH:

Insulin resistant, atherosclerosis-prone JCR:LA-cp rats were treated with 2-DG (0.3% w/w in chow) on an intermittent schedule (2 days treated, one day non-treated, two days treated and two days non-treated) or continuously at a dose to give an equivalent averaged intake.

KEY RESULTS:

Intermittent 2-DG-treatment improved insulin sensitivity, which correlated with increased adiponectin concentrations. Further, intermittent treatment (but not continuous treatment) reduced plasma levels of leptin and the inflammatory cytokine IL-1 beta. Both 2-DG treatments reduced micro-vascular glomerular sclerosis, but only the intermittent schedule improved macro-vascular dysfunction.

CONCLUSIONS AND IMPLICATIONS:

Our findings are consistent with reduction in severity of the metabolic syndrome and protection against end stage micro- and macro-vascular disease through intermittent metabolic deprivation at a cellular level by inhibition of glucose oxidation with 2-DG.

PMID:
17375078
PMCID:
PMC2013948
DOI:
10.1038/sj.bjp.0707226
[Indexed for MEDLINE]
Free PMC Article

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