Retraction notice to “Stimulation of sensory neurons by capsaicin increases tissue levels of IGF-I, thereby reducing reperfusion-induced apoptosis in mice” [Neuropharmacology, 52 (2007) 1303–1311]

We used proliferating primary cultures of immature rat Leydig cells expressing the recombinant human LH/choriogonadotropin (CG) receptor (LHR) to test the hypothesis that activation of this receptor inhibits apoptosis. We also compared the effects of LH/CG with epidermal growth factor (EGF) and IGF-I because these have been previously shown to stimulate proliferation and/or inhibit apoptosis in Leydig cells. Human CG (hCG), EGF, and IGF-I stimulated the phosphorylation of ERK1/2 and Akt in primary cultures of immature rat Leydig cells. These three hormones also robustly stimulated thymidine incorporation and inhibited drug-induced apoptosis. Using selective inhibitors of ERK1/2 (UO126) or Akt phosphorylation (LY294002), we show that the ERK1/2 and Akt cascades are both involved in the hCG- and EGF-dependent proliferation of Leydig cells, but only the ERK1/2 cascade is involved in their antiapoptotic actions. The same strategy showed that the proliferative and antiapoptotic actions of IGF-I are mediated entirely by the Akt pathway. These results show that activation of the LHR inhibits apoptosis in Leydig cells and that it does so through stimulation of the ERK1/2 pathway.

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Mechanism of IGF-I-stimulated glucose transport in human adipocytes. Demonstration of specific IGF-I receptors not involved in stimulation of glucose transport

Diabetes ◽

10.2337/diabetes.38.10.1217 ◽

1989 ◽

Vol 38 (10) ◽

pp. 1217-1225 ◽

Cited By ~ 9

Author(s):

M. K. Sinha ◽

C. Buchanan ◽

N. Leggett ◽

L. Martin ◽

P. G. Khazanie ◽

...

Keyword(s):

Glucose Transport ◽

Human Adipocytes ◽

Igf I ◽

Stimulation Of

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Role of insulin and IGF-I in activation of muscle protein synthesis after oral feeding

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1996.270.4.e614 ◽

1996 ◽

Vol 270 (4) ◽

pp. E614-E620 ◽

Cited By ~ 16

Author(s):

E. Svanberg ◽

H. Zachrisson ◽

C. Ohlsson ◽

B. M. Iresjo ◽

K. G. Lundholm

Keyword(s):

Protein Synthesis ◽

Skeletal Muscles ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Oral Feeding ◽

Myofibrillar Proteins ◽

Diabetic Mice ◽

Igf I ◽

Stimulation Of

The aim was to evaluate the role of insulin and insulin-like growth factor I (IGF-I) in activation of muscle protein synthesis after oral feeding. Synthesis rate of globular and myofibrillar proteins in muscle tissue was quantified by a flooding dose of radioactive phenylalanine. Muscle tissue expression of IGF-I mRNA was measured. Normal (C57 Bl) and diabetic mice (type I and type II) were subjected to an overnight fast (18 h) with subsequent refeeding procedures for 3 h with either oral chow intake or provision of insulin, IGF-I, glucose, and amino acids. Anti-insulin and anti-IGF-I were provided intraperitoneally before oral refeeding in some experiments. An overnight fast reduced synthesis of both globular (38 +/- 3%) and myofibrillar proteins (54 +/- 3%) in skeletal muscles, which was reversed by oral refeeding. Muscle protein synthesis, after starvation/ refeeding, was proportional and similar to changes in skeletal muscle IGF-I mRNA expression. Diabetic mice responded quantitatively similarly to starvation/refeeding in muscle protein synthesis compared with normal mice (C57 Bl). Both anti-insulin and anti-IGF-I attenuated significantly the stimulation of muscle protein synthesis in response to oral feeding, whereas exogenous provision of either insulin or IGF-I to overnight-starved and freely fed mice did not clearly stimulate protein synthesis in skeletal muscles. Our results support the suggestion that insulin and IGF-I either induce or facilitate the protein synthesis machinery in skeletal muscles rather than exerting a true stimulation of the biosynthetic process during feeding.

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Connections between thoraco-coxal proprioceptive afferents and motor neurons in the locust

Journal of Experimental Biology ◽

10.1242/jeb.203.3.435 ◽

2000 ◽

Vol 203 (3) ◽

pp. 435-445

Author(s):

M. Wildman

Keyword(s):

Electrical Stimulation ◽

Sensory Neurons ◽

Motor Neurons ◽

Chordotonal Organ ◽

Synaptic Connections ◽

Afferent Neurons ◽

Postsynaptic Potentials ◽

The Common ◽

Proprioceptive Afferents ◽

Stimulation Of

The position of the coxal segment of the locust hind leg relative to the thorax is monitored by a variety of proprioceptors, including three chordotonal organs and a myochordotonal organ. The sensory neurons of two of these proprioceptors, the posterior joint chordotonal organ (pjCO) and the myochordotonal organ (MCO), have axons in the purely sensory metathoracic nerve 2C (N2C). The connections made by these afferents with metathoracic motor neurons innervating thoraco-coxal and wing muscles were investigated by electrical stimulation of N2C and by matching postsynaptic potentials in motor neurons with afferent spikes in N2C. Stretch applied to the anterior rotator muscle of the coxa (M121), with which the MCO is associated, evoked sensory spikes in N2C. Some of the MCO afferent neurons make direct excitatory chemical synaptic connections with motor neurons innervating the thoraco-coxal muscles M121, M126 and M125. Parallel polysynaptic pathways via unidentified interneurons also exist between MCO afferents and these motor neurons. Connections with the common inhibitor 1 neuron and motor neurons innervating the thoraco-coxal muscles M123/4 and wing muscles M113 and M127 are polysynaptic. Afferents of the pjCO also make polysynaptic connections with motor neurons innervating thoraco-coxal and wing muscles, but no evidence for monosynaptic pathways was found.

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Insulin and insulin-like growth factor I signaling pathways in rainbow trout (Oncorhynchus mykiss) during adipogenesis and their implication in glucose uptake

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00457.2009 ◽

2010 ◽

Vol 299 (1) ◽

pp. R33-R41 ◽

Cited By ~ 30

Author(s):

L. Bouraoui ◽

E. Capilla ◽

J. Gutiérrez ◽

I. Navarro

Keyword(s):

Rainbow Trout ◽

Growth Factor ◽

Oncorhynchus Mykiss ◽

Glucose Uptake ◽

Signaling Pathways ◽

Mapk Phosphorylation ◽

Factor I ◽

Rainbow Trout Oncorhynchus Mykiss ◽

Igf I ◽

Stimulation Of

Primary cultures of rainbow trout ( Oncorhynchus mykiss ) adipocytes were used to examine the main signaling pathways of insulin and insulin-like growth factor I (IGF-I) during adipogenesis. We first determined the presence of IGF-I receptors (IGF-IR) and insulin receptors (IR) in trout preadipocytes ( day 5) and adipocytes ( day 14). IGF-IRs were more abundant and appeared to be in higher levels in differentiated cells than in preadipocytes, whereas IRs were detected in lower but constant levels throughout the culture. The cells were immunoreactive against ERK1/2 MAPK, and AKT/PI3K, components of the two main signal transduction pathways for insulin and IGF-I receptors. Stimulation of MAPK phosphorylation by IGF-I was higher in preadipocytes than in adipocytes, while no effects were observed in MAPK phosphorylation after incubation of cells with insulin. AKT phosphorylation increased in the presence of both insulin and IGF-I, with higher levels of stimulation in adipocytes than in preadipocytes. Activation of both pathways was blocked by the use of specific inhibitors of MAPK (PD98059) and AKT (wortmannin). We describe here, for the first time, the effects of IGF-I and insulin on 2-deoxyglucose uptake in primary culture of trout adipocytes. IGF-I was more potent in stimulating glucose uptake than insulin, and PD98059 and wortmannin inhibited the stimulation of glucose uptake by this growth factor, suggesting that IGF-I plays an important metabolic role in trout adipocytes. Our results suggest that differential activation of the MAPK and AKT pathways are involved in the IGF-I- and insulin-induced effects of trout adipocytes during the various stages of adipogenesis.

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Abstract 1359: Only the Catalytic p110alpha Isoform Mediates Class IA PI 3-Kinase-Induced Atherogenic Signals in Vascular Smooth Muscle Cells

Circulation ◽

10.1161/circ.118.suppl_18.s_313 ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Marius Vantler ◽

Lenard Mustafov ◽

Evren Caglayan ◽

Stephan Rosenkranz

Keyword(s):

Smooth Muscle ◽

Growth Factor ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Dna Synthesis ◽

Vascular Smooth Muscle Cells ◽

Fold Increase ◽

And Migration ◽

Induced Apoptosis ◽

Stimulation Of

Proliferation, migration, and apoptosis of vascular smooth muscle cells (VSMC) are pivotal determinants of the pathogenesis of vascular diseases, which are mainly controlled by growth factor dependent activation of PI 3-Kinase (PI3K). Growth factors like platelet-derived growth factor (PDGF) activate class IA PI3Ks containing one of three p110 catalytic subunits (p110alpha, p110beta, and p110delta). We investigated the specific function of these isoforms for PDGF-controlled proliferation, migration, and apoptosis of VSMC using novel isoform-specific inhibitors. PDGF-dependent proliferation and migration solely depended on p110alpha. Stimulation of VSMC with PDGF-BB (50 ng/ml) mediated a 2.5±0.4 increase ( p <0.05) of DNA-synthesis (BrdU incorporation assay) and induced a 3.4+/−0.7 fold increase ( p <0.05) of VSMC migration (modified Boyden-chamber). Inhibition of p110alpha with PIK075 (1 μ M, Ki=100 nM) completely abrogated PDGF-dependent DNA-synthesis and migration ( p <0,05), whereas inhibitors against p110beta (TGX 221, 1 μ M) or p110delta (IC87114 1 μ M) had no influence. Consistently, PDGF-induced DNA-synthesis and migration were suppressed by siRNA-dependent downregulation of p110alpha ( p <0,05) whereas p110beta or p110delta knockdown had no effect. Interestingly, stimulation of VSMC with PDGF-BB (50 ng/ml) induced anti- or proapoptotic effects depending on the duration of PDGFR activation. Incubation of VSMC with H 2 O 2 (50 μ M, 16h) led to a 2.8±0.7 fold increase ( p >0.05) of apoptosis (Cell Death Detection ELISA). Simultanous addition of PDGF-BB (50 ng/ml) significantly diminished the H 2 O 2 -induced apoptosis (52±7%, p >0.05). In contrast, prestimulation with PDGF-BB 24h prior to the addition of H 2 O 2 led to an increase of H 2 O 2 -induced apoptosis (7.8±1.3, p >0.05). The anti- as well as the proapoptotic effect depended strictly on p110alpha as PIK075 (1 μ M, p <0,05) or p110alpha specific siRNA completely abrogated PDGF-BB-mediated pro- as well as antiapoptotic effects. Our results demonstrate that only the catalytical PI3K subunit p110alpha mediates the growth factor-induced atherogenic responses. Therefore, p110alpha represents an interesting therapeutic target for prevention of atherosclerosis and restenosis formation.

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