The roles of receptor abnormalities in the pathogenesis and chronic complications of type 2 diabetes mellitus.
Type 2 diabetes mellitus is a polygenic disorder with complicated biochemical alterations. Numerous investigators have examined the implication of receptor abnormalities in the pathogenesis of the disorder. The authors review the potential roles of some important receptors, such as the insulin receptor, beta 3-adrenergic receptor, leptin receptor and peroxisome proliferator-activated receptor gamma, in the pathogenesis of human type 2 diabetes. They emphasize the significance of effective glycemic control by examining the evidence that strongly suggests the association of chronic complications of type 2 diabetes with abnormalities of receptors for the advanced glycation end products, transforming growth factor-beta and platelet-derived growth factor. The molecular understanding of receptor abnormalities and alterations in postreceptor signalling pathways may not only clarify the pathogenesis of human type 2 diabetes and the development of chronic complications in the disorder but also provide insight into more efficacious drug regimens that target these receptors.
Department of Pharmacology, Dalhousie University, Halifax, NS.
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Xiong
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JD
Gray
D002352:Carrier Proteins / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000503:physiopathology*; D017127:Glycation End Products, Advanced / Q000276:immunology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D011972:Receptor, Insulin / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D022702:Receptors, Adrenergic, beta-3; D011956:Receptors, Cell Surface / Q000502:physiology*; D018121:Receptors, Cytokine / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D018027:Receptors, Glucagon / Q000502:physiology; D054411:Receptors, Leptin; D017479:Receptors, Platelet-Derived Growth Factor / Q000502:physiology; D013453:Sulfonylurea Compounds / Q000276:immunology; D014157:Transcription Factors / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D002352:Carrier Proteins; D017127:Glycation End Products, Advanced; D007328:Insulin; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine; D018160:Receptors, Cytoplasmic and Nuclear; D018027:Receptors, Glucagon; D054411:Receptors, Leptin; D013453:Sulfonylurea Compounds; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D011972:Receptor, Insulin; D017479:Receptors, Platelet-Derived Growth Factor