The role of increased liver triglyceride content: a culprit of diabetic hyperglycaemia?
The role of fat in the aetiology of insulin resistance and type 2 diabetes has been re-considered in the present review. This is because of the questions raised by recent created mouse models imitating human lipodystrophy diabetes. It appears that hepatic steatosis, which is shared by both lipodystrophy and most if not all obesity patients, may play a key role in the pathogenesis of insulin resistance and type 2 diabetes despite the fact that lipodystrophy is an extreme state and occurs more rarely than obesity. The possible link between lipid and glucose metabolisms via peroxisome activity has been examined and its role in determining hyperglycaemia is suggested. Moreover, new avenues towards a better understanding of insulin resistance at the genomic level have also been proposed. It appears that one of the most fundamental biological phenomena, fuel selection, may underlie the causes of diabetic hyperglycaemia and perplex the role of fat in the aetiology of insulin resistance.
Song
Shaoming
S
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. ss1768@columbia.edu
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000209:etiology / Q000235:genetics; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000150:complications; D005943:Gluconeogenesis; D006801:Humans; D006943:Hyperglycemia / Q000209:etiology*; D007333:Insulin Resistance; D008060:Lipodystrophy / Q000150:complications / Q000235:genetics; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D020675:Peroxisomes / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors / Q000235:genetics; D014280:Triglycerides / Q000378:metabolism*
D001786:Blood Glucose; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; C497387:SREBF1 protein, human; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; C406806:Tg(AZIP-F)1Vsn protein, mouse; D014157:Transcription Factors; D014280:Triglycerides