Biochemical pathways for microvascular complications of diabetes mellitus.
OBJECTIVE
To review the current biochemical theories on how diabetes contributes to microvascular disease.


METHODS
MEDLINE search (1980-June 2003) and bibliographies of articles obtained on this topic.


METHODS
Articles identified from the data sources were evaluated and those deemed relevant to this review were incorporated.


RESULTS
The prevailing biochemical theories on how diabetes leads to microvascular disease include increased polyol (sorbitol/aldose reductase) pathway flux, production of advanced glycation end-products, generation of reactive oxygen species, and activation of diacylglycerol and protein kinase C isoforms. These pathways contribute to endothelial damage and dysfunction and may alter gene functioning.


CONCLUSIONS
Each pathway, via varied and often overlapping mechanisms, contributes to altered microvascular function that leads to the development of retinopathy, neuropathy, and nephropathy, the major microvascular complications associated with diabetes.
Setter
Stephen M
SM
Department of Pharmacotherapy, College of Pharmacy, Washington State University/Elder Services, Spokane, WA, USA. ssetter@smhca.org
Campbell
R Keith
RK
Cahoon
Clifton J
CJ
D000818:Animals; D003920:Diabetes Mellitus / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008833:Microcirculation / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D017382:Reactive Oxygen Species; D005947:Glucose