Tolrestat and epalrestat have been characterized as noncompetitive inhibitors of aldo-ketone reductase 1B1 (AKR1B1), a leading drug target for the treatment of type 2 diabetes complications.
In fact, serum albumin may undergo structural changes by glycation which impacts on its function and plays a major role in the genesis of diabetes mellitus complications.
In this review, we summarise the current understanding of the molecular mechanisms involved in pyroptosis, as well as recent advances in the role of NLRP3 inflammasome activation and pyroptosis in the development of diabetes and diabetic complications.
Patients with mutations of the insulin receptor gene (INSR) have extreme insulin resistance and are at risk for early morbidity and mortality from diabetes complications.
In this study, we measured the ratio in elderly patients with diabetes and evaluated its association with diabetic complications and disability in activities of daily living (ADL disability).
Long noncoding RNA KCNQ1OT1 is involved in pathophysiological mechanisms of diabetic complications, including diabetic cardiomyopathy and diabetic retinopathy.
Key findings are that (a) low doses of Nasonia venom elevate sorbitol levels in human renal mesangial cells (HRMCs) without changing glucose or fructose levels; (b) venom is a much more potent inducer of sorbitol elevation than glucose; (c) low venom doses significantly alter expression of genes involved in sterol and alcohol metabolism, transcriptional regulation, and chemical/stimulus response; (d) although venom treatment does not alter expression of the key sorbitol pathway gene aldose reductase (AR); (e) venom elevates expression of a related gene implicated in diabetes complications (AKR1C3) as well as the fructose metabolic gene (GFPT2).
To develop multifunctional aldose reductase (AKR1B1) inhibitors for anti-diabetic complications, a novel series of 2-phenoxypyrido[3,2-<i>b</i>]pyrazin-3(4<i>H</i>)-one derivatives were designed and synthesised.
Humans exhibit three members of the AKR1B subfamily: AKR1B1 (aldose reductase, participates in diabetes complications), AKR1B10 (overexpressed in several cancer types), and the recently described AKR1B15.
Aldose reductase (AR), a member of aldo-keto reductase family, is the rate-limiting enzyme in the polyol pathway, and is known to play a key role in the pathogenesis of diabetic complications.
Subtle involvement of ALR2 in invoking various pathways of diabetic complications has caused an increase in attention towards the identification of novel aldose reductase inhibitors (ARIs).
Several ALR2 inhibitors with a promising pre-clinical ability to address diabetic complications and inflammatory diseases are being developed during the observed timeframe.
The haptoglobin (Hp) genotype is associated with type 2 diabetes related complications including increased risk for cerebrovascular pathology and worse cognitive performance.
Prolonged autoimmune injures in the retinal territory will triggers and maintains a low-grade chronic inflammation process, microvascular alterations, glial proliferation and subsequent fibrosis and worse, progressive apoptosis of the photoreceptor neurons.Patients with long-standing DM disturbances in retinal BRBs suffer of alterations in the enzymatic pathways of polyunsaturated fatty acids (PUFAs), increase release of free radicals and pro-inflammatory molecules and subsequently incremented levels of vascular endothelial growth factor.
Our results revealed that six key pathways might be associated with longevity, including the longevity-regulating pathway, the peroxisome pathway, the mTOR-signalling pathway, the FOXO-signalling pathway, the AGE-RAGE-signalling pathway in diabetic complications, and the TGF-beta-signalling pathway.