IRS proteins and diabetic complications.

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Term Occurence Count Dictionary
Insulin 6 endocrinologydiseasesdrugs
diabetic neuropathy 10 endocrinologydiseases
diabetic retinopathy 8 endocrinologydiseases
obesity 3 endocrinologydiseases
pioglitazone 1 endocrinologydiseasesdrugs

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Select Drug Character Offset Drug Term Instance
Insulin 1982 diabetic retinopathy• IRS proteins in the brain• IRS proteins in diabetic neuropathyIntroduction Insulin and IGF signalling require a family of scaffold proteins (IRS proteins) to integrate extracellular signals
Insulin 4415 decrease the risk of non-fatal heart attack, stroke or death from CVD by 57% in diabetic patients [[8]]. Insulin has been proposed to mediate an anti-atherogenic effect on blood vessels via IRS–PI3K–Akt signalling
Insulin 8783 however, total IRS1 was unchanged in individuals with type 2 diabetes and left ventricular dysfunction. Insulin -induced Akt phosphorylation was greater in control mice than in ob/ob mice with no alterations in total
Insulin 13714 hypertension, using ACE inhibitors or angiotensin II receptor blockers as the mainstays of therapy [[29]]. Insulin signalling plays a critical role in kidney cell physiology and in the maintenance of the glomerular
Insulin 17705 pathwayFornoni et al (2006) [[80]]IRS2Wild-type, Irs1−/− and Irs2−/− miceProximal tubule epithelial cells Insulin -induced increases in tubular bicarbonate ion absorption and Akt phosphorylation were seen in wild-type
Insulin 33092 [[72]]. Impaired insulin signalling has been implicated in the pathogenesis of diabetic neuropathy. Insulin is a neurotrophic factor for the dorsal root ganglion, and IRS proteins are expressed in these cells,
pioglitazone 26117 potentially improving diabetic retinopathy outcomes. Supporting this hypothesis, two reports indicated that pioglitazone , a peroxisome proliferator-activated receptor-γ (PPARγ) agonist reduced TNF-α-mediated IRS1Ser307
Select Disease Character Offset Disease Term Instance
diabetic neuropathy 1951 nephropathy• IRS proteins in diabetic retinopathy• IRS proteins in the brain• IRS proteins in diabetic neuropathy IntroductionInsulin and IGF signalling require a family of scaffold proteins (IRS proteins) to integrate
diabetic neuropathy 32450 that targeting these changes may improve outcomes for Alzheimer’s patients [[66]].IRS proteins in diabetic neuropathy Diabetic neuropathy is a common complication of diabetes, affecting 50% of patients. Many patients suffer
diabetic neuropathy 32848 cases require amputation [[70]]. Many different pathways have been implicated in the pathogenesis of diabetic neuropathy , including decreased neurotrophic growth factors such as IGF-1 [[71]], advanced glycation end-products
diabetic neuropathy 33071 and oxidative stress [[72]]. Impaired insulin signalling has been implicated in the pathogenesis of diabetic neuropathy . Insulin is a neurotrophic factor for the dorsal root ganglion, and IRS proteins are expressed in these
diabetic neuropathy 33752 incretin drugs that are widely used to treat type 2 diabetes have been shown to reduce the severity of diabetic neuropathy in pre-clinical models. Exendin-4, vildagliptin and alogliptin all improved nerve conductance velocity
diabetic neuropathy 34322 expression would seem to be a useful avenue for exploring new and improved therapeutic interventions in diabetic neuropathy .Table 4Summary of animal model data implicating IRS proteins in diabetic neuropathyIRS involvedRodent
diabetic neuropathy 34406 interventions in diabetic neuropathy.Table 4Summary of animal model data implicating IRS proteins in diabetic neuropathy IRS involvedRodent genotype/phenotypeOrgan affectedMain finding(s)ReferenceIR, IRS1ob/ob mice (model
diabetic neuropathy 37507 (2001) [[87]]CREB, cAMP response element binding protein; GK, Goto–Kakizaki (rats); PDN, painful diabetic neuropathy ; ZDF, Zucker diabetic fatty (rats)Concluding remarksA summary of the role of IRS proteins in organs
diabetic neuropathy 39480 nephropathy (purple panel), diabetic retinopathy (green panel), diabetic vascular disease (yellow panel), diabetic neuropathy (orange panel) and Alzheimer’s disease (blue panel). Details and supporting references are provided
diabetic neuropathy 39790 arrow represents ‘leading to’. AngII, angiotensin II; βAR, β-adrenergic receptor; PDN, painful diabetic neuropathy y
diabetic retinopathy 1882 IRS proteins and cardiovascular disease• IRS proteins and diabetic nephropathy• IRS proteins in diabetic retinopathy • IRS proteins in the brain• IRS proteins in diabetic neuropathyIntroductionInsulin and IGF signalling
diabetic retinopathy 23855 increasing IRS2 levels in the diabetic kidney using similar hypoxia-mediated strategies.IRS proteins in diabetic retinopathy Diabetic retinopathy is a common microvascular complication of diabetes characterised by damage to a
diabetic retinopathy 24116 retinal pigment epithelia, Müller cells and retinal vascular cells [[45]]. A significant feature of diabetic retinopathy is the loss of retinal blood vessels, leading to retinal ischaemia/hypoxia and then to pathogenic neovascularisation
diabetic retinopathy 24417 in the normal retina, and both IRS1 and IRS2 have been implicated in normal retinal development and diabetic retinopathy . Some of these data are discussed below.Retinal Müller cells: a primary site of IRS signalling in the
diabetic retinopathy 25859 (SOCS3)-mediated targeting to the proteasome [[54]]. Given the critical role of retinal capillary loss during diabetic retinopathy pathogenesis, these data provide evidence that rescuing insulin signalling may decrease retinal endothelial
diabetic retinopathy 26031 rescuing insulin signalling may decrease retinal endothelial cell apoptosis, thus potentially improving diabetic retinopathy outcomes. Supporting this hypothesis, two reports indicated that pioglitazone, a peroxisome proliferator-activated
diabetic retinopathy 26897 disease. A summary of these data is shown in Table 3.Table 3Summary of data linking IRS proteins to diabetic retinopathy IRS involvedRodent genotype/phenotypeOrgan affectedMain findingsReferenceIRS2Irs2−/− miceEye (retina)Irs2
diabetic retinopathy 39402 changes in IRS proteins during diabetic heart disease (pink panel), diabetic nephropathy (purple panel), diabetic retinopathy (green panel), diabetic vascular disease (yellow panel), diabetic neuropathy (orange panel) and Alzheimer’s
obesity 12629 above. IRS proteins may play a role in the response of neurons to ischaemia, as in a mouse model of obesity -induced type 2 diabetes there was reduced IRS to PI3K to Akt signalling in the brain [[27]]. In a recent
obesity 30299 hepatic glucose production [[60]]. Mice lacking the IR in neurons (NIRKO mice) developed diet-sensitive obesity , with increased body fat and plasma leptin levels [[61]]. Female mice lacking IRS2 are infertile, due
obesity 30732 homeostasis, as mice lacking IRS2 in a specific subset of hypothalamic neurons display hyperphagia, obesity and increased body length [[63]]. Whole-body Irs2−/− mice have brains that are 30% smaller than

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