Peripheral insulin resistance and impaired action are the primary characteristics of type 2 diabetes. The first observable defect in this major disorder occurs muscle, where glucose disposal response to is impaired. We have developed a transgenic mouse with dominant-negative insulin-like growth factor-I receptor (KR–IGF-IR) specifically targeted skeletal muscle. Expression KR–IGF-IR resulted formation hybrid receptors between mutant endogenous IGF-I receptors, thereby abrogating normal...

Insulin and insulin-like growth factor (IGF-I) receptors are heterotetrameric proteins consisting of two α- β-subunits members the transmembrane tyrosine kinase receptors. Specific ligand binding to receptor triggers a cascade intracellular events, which begins with autophosphorylation several residues β-subunit receptor. The triple cluster in domain is earliest major site. Previous studies have shown that substitutions these three tyrosines by phenylalanines both insulin IGF-I practically...

Early neurogenesis progresses by an initial massive proliferation of neuroepithelial cells followed a sequential differentiation the various mature neural cell types. The regulation these processes growth factors is poorly understood. We intend to understand, in well-defined biological system, embryonic chicken retina, role insulin-related neurogenesis. demonstrate local presence signaling elements together with response factors. Neuroretina at days 6-8 development (E6-E8) expressed...

Insulin-like growth factor-I receptor (IGF-IR) gene expression is regulated by various stimuli, including hormones, factors, and nutritional status. We have investigated the molecular mechanism which two insulin-like (IGF-I) basic fibroblast factor (bFGF) regulate IGF-IR expression. bFGF increases endogenous mRNA levels promoter activity. This effect mediated a region of located between nucleotides −476 −188 in 5′-flanking region. In contrast, IGF-I decreases levels. down-regulates...

The molecular phylogeny of the vertebrate insulin receptor (IR) family was reconstructed under maximum likelihood (ML) to establish homologous relationships among its members. A sister group relationship between orphan insulin–related (IRR) and insulin-like growth factor 1 (IGF1R) exclusion IR obtained maximal bootstrap support. Although both IGF1R were identified in all vertebrates, IRR could not be found any teleost fish. ancestral character states at each position molecule inferred for...

The ability of the sulfonylurea receptor (SUR) 1 to suppress seizures and excitotoxic neuron damage was assessed in mice transgenically overexpressing this receptor. Fertilized eggs from FVB were injected with a construct containing SUR cDNA calcium-calmodulin kinase IIα promoter. resulting showed normal gross anatomy, brain morphology histology, locomotor cognitive behavior. However, they overexpressed SUR1 transgene, yielding 9- 12-fold increase density [ 3 H]glibenclamide binding cortex,...

Abstract To better understand the role of insulin‐related growth factors in neural development, we have characterized by situ hybridization chicken embryonic retina patterns gene expression for insulin, insulin‐like factor I (IGF‐I), their respective receptors and IGF binding protein 5 (IGFBP5) from early stages (E6) until late (E18)‐an analysis not performed yet any species. In addition, studied effect insulin IGF‐I on cultured neuroepithelial cells. Insulin receptor mRNA were both present...

The aryl hydrocarbon receptor (AhR) is a ligand‐activated transcription factor, largely known for its role in xenobiotic metabolism and detoxification as well crucial regulator of inflammation. Here, we have compared cohort wild‐type AhR‐null mice along aging to study the relationship between this age‐associated inflammation, termed “inflammaging,” both at systemic CNS level. Our results show that AhR deficiency associated with premature aged phenotype, characterized by early inflammaging,...

Retinitis pigmentosa (RP) is a group of hereditary retinal neurodegenerative conditions characterized by primary dysfunction and death photoreceptor cells, resulting in visual loss and, eventually, blindness. To date, no effective therapies have been transferred to clinic. Given the diverse genetic etiology RP, targeting common cellular molecular alterations has emerged as potential therapeutic strategy. Using Pde6b rd10/rd10 mouse model we investigated effects daily intraperitoneal...

Apart from transcription factors, little is known about the molecules that modulate proliferation and differentiation of pancreatic endocrine cells. The early expression tyrosine hydroxylase (TH) in a subset glucagon(+) cells led us to investigate whether catecholamines have role beta cell development.We studied immunohistochemical characteristics TH-expressing wild-type (Th (+/+) ) mice during pancreas development, analysed phenotype TH-deficient (-/-) mice. We also effect dopamine addition...

Purpose: The induction of proinsulin expression by transgenesis or intramuscular gene therapy has been shown previously to retard retinal degeneration in mouse and rat models retinitis pigmentosa (RP), a group inherited conditions that result visual impairment. We investigated whether intraocular treatment with biodegradable poly (lactic-co-glycolic) acid microspheres (PLGA-MS) loaded cellular functional neuroprotective effects the retina. Methods: Experiments were performed using Pde6brd10...

Abstract ProNGF signaling through p75 NTR has been associated with neurodegenerative disorders. Retinitis pigmentosa (RP) comprises a group of inherited retinal dystrophies that causes progressive photoreceptor cell degeneration and death, at rate dependent on the genetic mutation. There are more than 300 mutations causing RP, this is challenge to therapy. Our study was designed explore common mechanism for in progression assess its potential value as therapeutic target. The proNGF/p75...

Retinitis pigmentosa (RP) is an inherited retinal dystrophy that courses with progressive degeneration of tissue and loss vision. Currently, RP unpreventable, incurable condition. We propose glycogen synthase kinase 3 (GSK-3) inhibitors as potential leads for cell neuroprotection, since the retina also a part central nervous system GSK-3 are potent neuroprotectant agents. Using chemical genetic approach, diverse small molecules different potency binding mode to have been used validate...

We have chosen a vertebrate model accessible during neurulation, the chick, for analysis of endogenous insulin signaling and its contribution to early embryonic cell survival. Unlike rodents, humans chickens single preproinsulin gene, facilitating prepancreatic expression characterization. show that in vivo interference with using antisense oligonucleotides against receptor increases apoptosis neurulation. In contrast, high glucose administration does not increase level culture or vivo....

Tyrosine hydroxylase (TH) is the first and rate-limiting enzyme in catecholamine biosynthesis. Whereas neuroendocrine roles of cathecolamines postnatally are well known, presence function TH organogenesis unclear. The aim this study was to define expression during cardiac development unravel role it may play heart formation. We studied chick embryos by whole mount situ hybridization quantitative reverse transcription-polymerase chain reaction analysed activity high-performance liquid...

The ATP-sensitive potassium channels (K+ATP channels) are heteromultimeric structures formed by a member of the sulfonylurea receptor (SUR) family and inwardly rectifying channel (Kir6.x). K+ATP play an essential role in nutrient-induced insulin secretion from pancreatic β-cell. We have cloned characterized promoter region mouse SUR1 gene, shown that it lacks CAAT TATA boxes or initiator element. Studies transcription initiation several tissues showed there is common brain, heart, pancreas...

Abstract Transforming growth factor (TGF)‐β and insulin display opposite effects in regulating programmed cell death during vertebrate retina development; the former induces apoptosis while latter prevents it. In present study we investigated coordinated actions of TGF‐β an organotypic culture system early postnatal mouse retina. Addition exogenous resulted a significant increase whereas attenuated was capable blocking TGF‐β‐induced apoptosis. This effect appeared to be modulated via...