Chapter 20 Retinal Insulin Receptor Signaling In Hyperosmotic Stress

Rajala, Raju V S; Ivanovic, Ivana; Dilly, Ashok K.

doi:10.1016/s0083-6729(08)00620-1

Cited by 9 publications

(7 citation statements)

References 72 publications

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“…IR activation has been shown to rescue retinal neurons from apoptosis through a phosphoinositide 3-kinase and protein kinase B (Akt) survival cascade. The study of the retinal IR signaling in sorbitol-treated retinas ex vivo shows that sorbitol activates both the IR and IGF1R tyrosine kinases, which leads to the activation of PI3K and Akt survival pathway in the retina (Rajala et al, 2009). MIM: 147670 ORPHA122664 Donohue syndrome; Rabson–Mendenhall syndrome; Insulin-resistant diabetes mellitus with acanthosis nigricans; Familial hyperinsulinemic hypoglycemia-5. SIGNAL TRANSDUCTION Camk4 (calcium/calmodulin-dependent protein kinase IV) −1, 3CaMKIV–CREB pathway is crucial for osteoclast differentiation and function.In sections of the adult gerbil inner ear, moderate to strong immunoreactivity for Camk4 was present along the lateral borders of OHCs (Koyama et al, 1999) and in the SG (Bok et al, 2007).…”

Section: Table A1mentioning

confidence: 99%

Section: Table A1mentioning

confidence: 99%

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The Role of Insulin-Like Growth Factor-I in the Physiopathology of Hearing

Murillo-Cuesta¹,

Rosa²,

Cediel³

et al. 2011

Front. Mol. Neurosci.

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Insulin-like growth factor-I (IGF-I) belongs to the family of polypeptides of insulin, which play a central role in embryonic development and adult nervous system homeostasis by endocrine, autocrine, and paracrine mechanisms. IGF-I is fundamental for the regulation of cochlear development, growth, and differentiation, and its mutations are associated with hearing loss in mice and men. Low levels of IGF-I have been shown to correlate with different human syndromes showing hearing loss and with presbyacusis. Animal models are fundamental to understand the genetic, epigenetic, and environmental factors that contribute to human hearing loss. In the mouse, IGF-I serum levels decrease with aging and there is a concomitant hearing loss and retinal degeneration. In the Igf1−/− null mouse, hearing loss is due to neuronal loss, poor innervation of the sensory hair cells, and age-related stria vascularis alterations. In the inner ear, IGF-I actions are mediated by intracellular signaling networks, RAF, AKT, and p38 MAPK protein kinases modulate the expression and activity of transcription factors, as AP1, MEF2, FoxM1, and FoxP3, leading to the regulation of cell cycle and metabolism. Therapy with rhIGF-I has been approved in humans for the treatment of poor linear growth and certain neurodegenerative diseases. This review will discuss these findings and their implications in new IGF-I-based treatments for the protection or repair of hearing loss.

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Section: Table A1mentioning

confidence: 99%

Section: Table A1mentioning

confidence: 99%

The Role of Insulin-Like Growth Factor-I in the Physiopathology of Hearing

Murillo-Cuesta¹,

Rosa²,

Cediel³

et al. 2011

Front. Mol. Neurosci.

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“…A canonical Akt survival pathway has been shown to be constitutively active in cone photoreceptors ( 276 ). However, rod photoreceptors express the active form of Akt only transiently during the exposure to conditions such as physiological light ( 61 ), oxidative ( 269 ), hyperosmotic ( 277 ), or light stress ( 135 ). In mouse models of retinitis pigmentosa having genetic mutations in rods, the active form of Akt stays expressed until the photoreceptors die ( 109 ).…”

Section: Phosphoinositide Signaling In Cone Photoreceptorsmentioning

confidence: 99%

Phosphoinositide 3-kinase signaling in the vertebrate retina

Rajala

2010

Journal of Lipid Research

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This article is available online at http://www.jlr.org was established by Streb et al. ( 3 ) in their classic paper that showed elevations in IP 3 caused intracellular release of bound calcium. Subsequently, 1,2-DG was found to stimulate protein kinase C (PKC), a serine/threonine kinase that phosphorylates a number of cellular proteins ( 4 ). Activation of the PLC/PKC cascade affects a variety of cellular events, including secretion, phagocytosis, smooth muscle contraction, proliferation, neurotransmission, and metabolism [see reviews by Rhee ( 5 ), Rhee and Choi ( 6 ), and Berridge ( 7 ) THE PI CYCLEIn the early 1950s, Hokin and Hokin ( 1, 2 ) discovered that addition of acetylcholine to brain slices stimulated the incorporation of phosphate and inositol but not glycerol into lipids; the major products of this incorporation were phosphatidylinositol (PI) and phosphatidic acid. Subsequent studies defi ned the reactions of the PI cycle and showed that the initial event was receptor-meditated activation of a phospholipase C (PLC), which hydrolyzes phosphatidylinositol 4,5-bisphosphate (PI-4,5-P 2 ) to 1,2-diacylglycerol (DG) and inositol 1,4,5-trisphosphate (IP 3 ). This increase in lipid synthesis reported by the Hokins was a recovery reaction that rapidly replenished PI separate from de novo PI synthesis. The role of 1,4, This work was supported by grants

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“…However, no retina phenotype was reported in this study. Furthermore, Akt2 is activated in the retinas of mice following sorbitolinduced hyperosmotic stress, which mimics aspects of diabetic hyperglycemia 40 . However, a contribution for Akt2 expression in the RPE to the development of DR has not been demonstrated.…”

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Reducing Akt2 in retinal pigment epithelial cells causes a compensatory increase in Akt1 and attenuates diabetic retinopathy

et al. 2022

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The retinal pigment epithelium (RPE) plays an important role in the development of diabetic retinopathy (DR), a leading cause of blindness worldwide. Here we set out to explore the role of Akt2 signaling—integral to both RPE homeostasis and glucose metabolism—to DR. Using human tissue and genetically manipulated mice (including RPE-specific conditional knockout (cKO) and knock-in (KI) mice), we investigate whether Akts in the RPE influences DR in models of diabetic eye disease. We found that Akt1 and Akt2 activities were reciprocally regulated in the RPE of DR donor tissue and diabetic mice. Akt2 cKO attenuated diabetes-induced retinal abnormalities through a compensatory upregulation of phospho-Akt1 leading to an inhibition of vascular injury, inflammatory cytokine release, and infiltration of immune cells mediated by the GSK3β/NF-κB signaling pathway; overexpression of Akt2 has no effect. We propose that targeting Akt1 activity in the RPE may be a novel therapy for treating DR.

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Chapter 20 Retinal Insulin Receptor Signaling In Hyperosmotic Stress

Cited by 9 publications

References 72 publications

The Role of Insulin-Like Growth Factor-I in the Physiopathology of Hearing

The Role of Insulin-Like Growth Factor-I in the Physiopathology of Hearing

Phosphoinositide 3-kinase signaling in the vertebrate retina

Reducing Akt2 in retinal pigment epithelial cells causes a compensatory increase in Akt1 and attenuates diabetic retinopathy

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