Alcohol-related diols cause acute insulin resistance in vivo

Xu, Dan; Dhillon, Amardeep S.; Abelmann, Anke; Croft, Kevin; Peters, Timothy J.; Norman Palmer, T.

« Previous Next »Metabolism - Clinical and Experimental
Volume 47, Issue 10 , Pages 1180-1186, October 1998

Alcohol-related diols cause acute insulin resistance in vivo☆

Dan Xu
- Departments of Biochemistry and Medicine, University of Western Australia, Nedlands, Western Australia, Australia
- Department of Clinical Biochemistry, King's College School of Medicine and Dentistry, London, UK
- School of Biomedical and Molecular Sciences, James Cook University, Townsville, Queensland, Australia
Amardeep S. Dhillon
- Departments of Biochemistry and Medicine, University of Western Australia, Nedlands, Western Australia, Australia
- Department of Clinical Biochemistry, King's College School of Medicine and Dentistry, London, UK
- School of Biomedical and Molecular Sciences, James Cook University, Townsville, Queensland, Australia
Anke Abelmann
- Departments of Biochemistry and Medicine, University of Western Australia, Nedlands, Western Australia, Australia
- Department of Clinical Biochemistry, King's College School of Medicine and Dentistry, London, UK
- School of Biomedical and Molecular Sciences, James Cook University, Townsville, Queensland, Australia
Kevin Croft
- Departments of Biochemistry and Medicine, University of Western Australia, Nedlands, Western Australia, Australia
- Department of Clinical Biochemistry, King's College School of Medicine and Dentistry, London, UK
- School of Biomedical and Molecular Sciences, James Cook University, Townsville, Queensland, Australia
Timothy J. Peters
- Departments of Biochemistry and Medicine, University of Western Australia, Nedlands, Western Australia, Australia
- Department of Clinical Biochemistry, King's College School of Medicine and Dentistry, London, UK
- School of Biomedical and Molecular Sciences, James Cook University, Townsville, Queensland, Australia
T. Norman Palmer
- Address reprint requests to T. Norman Palmer, Chancellery, James Cook University, Townsville, Queensland 4811, Australia.
- Departments of Biochemistry and Medicine, University of Western Australia, Nedlands, Western Australia, Australia
- Department of Clinical Biochemistry, King's College School of Medicine and Dentistry, London, UK
- School of Biomedical and Molecular Sciences, James Cook University, Townsville, Queensland, Australia

Received 17 April 1997; accepted 22 April 1998.

Abstract

Epidemiological studies suggest that alcohol consumption is an independent risk factor for the development of non—insulin-dependent diabetes mellitus (NIDDM). Alcoholism is known to be associated with increased plasma levels of two novel diols, 2,3-butanediol and 1,2-propanediol, metabolites known to impair insulin action in isolated adipocytes. This study examines whether 2,3-butanediol and 1,2-propanediol have the capacity to impair insulin action acutely in vivo in the rat. Using the euglycemic-hyperinsulinemic clamp, it is shown that the two diols reduce whole-body glucose utilization (by ∼30%), with the onset of insulin resistance in vivo occurring at plasma concentrations of 2,3-butanediol (33 μmol/L) at least one order of magnitude (P < .001) lower than 1,2-propanediol (432 μmol/L). Tracer methodologies using [U-¹⁴C]glucose and 2-deoxy[1-³H]glucose indicate that the reduction in whole-body glucose utilization is accompanied by a reduction in glucose uptake and glycogen synthesis in the skeletal muscle and heart. The association between elevated plasma diol levels and insulin resistance demonstrated in this report raises the question of whether there is a link between he high plasma diol levels in alcohol abusers and their increased susceptibility to NIDDM.

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☆ Supported by the National Health and Medical Research Council, Clive and Vera Ramaciotti Foundation, and Diabetes Research Foundation of Western Australia.

PII: S0026-0495(98)90320-1

« Previous Next »Metabolism - Clinical and Experimental
Volume 47, Issue 10 , Pages 1180-1186, October 1998

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