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1.
Sci Rep ; 14(1): 9852, 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38684874

RESUMEN

We show that nearly-degenerate Vertical External-Cavity Surface-Emitting Lasers may emit a set of tilted beams of individually addressable mode-locked pulses. These time localized beams feature a Gaussian profile and they are emitted in pairs with opposite transverse k-vector. Because they are phase locked, their interference leads to a non homothetic pattern in the near-field emission of the laser. In the simplest situation, when a single pair is emitted, this is a stripe pattern. Our analysis discloses the role of third order (spherical) aberrations of the cavity in stabilizing this spatio-temporal mode-locked regime and in selecting the value of the transverse k-vector.

2.
Opt Lett ; 46(5): 1109-1112, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33649669

RESUMEN

We analyze the effect of optical feedback on the dynamics of an external-cavity passively mode-locked surface-emitting laser operating in the regime of temporal localized structures. Depending on the ratio between the cavity round trip time and the feedback delay, we show experimentally that feedback acts as a solution selector that either reinforces or hinders the appearance of one of the multistable harmonic arrangements of pulses. Our theoretical analysis reproduces well the experiment and allows us to evidence asymmetrical resonance tongues due to the parity symmetry-breaking induced by gain depletion.

3.
Phys Rev Lett ; 123(4): 043902, 2019 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-31491283

RESUMEN

Time-delayed dynamical systems materialize in situations where distant, pointwise, nonlinear nodes exchange information that propagates at a finite speed. However, they are considered devoid of dispersive effects, which are known to play a leading role in pattern formation and wave dynamics. We show how dispersion may appear naturally in delayed systems and we exemplify our result by studying theoretically and experimentally the influence of third order dispersion in a system composed of coupled optical microcavities. Dispersion-induced pulse satellites emerge asymmetrically and destabilize the mode-locking regime.

4.
Opt Lett ; 43(21): 5367-5370, 2018 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-30383009

RESUMEN

Temporal localized states (TLSs) are individually addressable structures traveling in optical resonators. They can be used to obtain bits of information and generate frequency combs with tunable spectral density. We show that a pair of specially designed nonlinear mirrors, a 1/2 vertical-cavity surface-emitting laser and a semiconductor saturable absorber, coupled in self-imaging conditions, can lead to the generation of such TLSs. Our results indicate how a conventional passive mode-locking scheme can be adapted to provide a robust and simple system emitting TLSs and paves the way towards the observation of three dimensional confined states, the so-called light bullets.

5.
Rev Sci Instrum ; 87(8): 083109, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27587102

RESUMEN

The integration of an industry ready packaged Sb-based Vertical-External-Cavity Surface-Emitting-Laser (VECSEL) into a Cavity Ring Down Spectrometer (CRDS) is presented. The instrument operates in the important 2.3 µm atmospheric transparency window and provides a high sensitivity (minimum detectable absorption of 9 × 10(-11) cm(-1)) over a wide spectra range. The VECSEL performances combine a large continuous tunability over 120 cm(-1) around 4300 cm(-1) together with a powerful (∼5 mW) TEM00 diffraction limited beam and linewidth at MHz level (for 1 ms of integration time). The achieved performances are illustrated by high sensitivity recordings of the very weak absorption spectrum of water vapor in the region. The developed method gives potential access to the 2-2.7 µm range for CRDS.

6.
Opt Lett ; 40(18): 4301-4, 2015 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-26371921

RESUMEN

We report on the highly coherent modeless broadband continuous wave operation of a semiconductor vertical-external-cavity-surface-emitting laser. The laser design is based on a frequency-shifted-feedback scheme provided by an acousto-optic frequency shifter inserted in a linear or a ring traveling wave cavity. The gain mirror is a GaAs-based multiple quantum well structure providing large gain at 1.07 µm. This laser exhibits a coherent optical spectrum over 1.27 nm (330 GHz) bandwidth, with 70 mW output power and a high beam quality. The light polarization is linear (>30 dB extinction ratio). The laser dynamics exhibits a low intensity noise close to class A regime, with a ∼1.5 MHz cutoff frequency. The frequency noise spectral density shows a first-order low-pass like shape (130 kHz cutoff) leading to a Gaussian shape for homodyne interferometric signals. The measured beat width is ≃54 kHz and the coherence time of ∼19 µs. No nonlinear effects are observed, showing dynamics very close to theory.

7.
Opt Express ; 22(5): 5962-76, 2014 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-24663933

RESUMEN

We demonstrate a high reflectivity (> 99%), low-loss (< 0.1%) and aberrations-free (2% of λ rms phase fluctuations) concave Bragg mirror (20mm radius of curvature) integrating a photonic crystal with engineered spherical phase and amplitude transfer functions, based on a III-V semiconductors flat photonics technology. This mirror design is of high interest for highly coherent high power stable external cavity semiconductor lasers, exhibiting very low noise. We design the photonic crystal for operation in the pass band. The approach incorporates spatial, spectral (filter bandwidth= 5nm) and polarization filtering capabilities. Thanks to the mirror, a compact single mode TEM(00) 2mm-long air gap high finesse (cold cavity Q-factor 10(6) - 10(7)) stable laser cavity is demonstrated with a GaAs-based quantum-wells 1/2-VCSEL gain structure at 1µm. Excellent laser performances are obtained in single frequency operation: low threshold density of 2kW/cm(2) with high differential efficiency (21%). And high spatial, temporal and polarization coherence: TEM(00) beam close to diffraction limit, linear light polarization (> 60dB), Side Mode Suppression Ratio > 46dB, relative intensity noise at quantum limit (< -150dB) in 1MHz-84GHz radio frequency range, and a theoretical linewidth fundamental limit at 10 Hz (Q-factor ∼ 3.10(13)).

8.
Opt Express ; 18(20): 21330-41, 2010 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-20941029

RESUMEN

We present a method to experimentally characterize the gain filter and calculate a corresponding parabolic gain bandwidth of lasers that are described by "class A" dynamics by solving the master equation of spectral condensation for Gaussian spectra. We experimentally determine the gain filter, with an equivalent parabolic gain bandwidth of up to 51 nm, for broad-band InGaAs/GaAs quantum well gain surface-emitting semiconductor laser structures capable of producing pulses down to 60 fs width when mode-locked with an optical Stark saturable absorber mirror.

9.
Opt Express ; 18(14): 14627-36, 2010 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-20639948

RESUMEN

We demonstrate high power (2.1W) low noise single frequency operation of a tunable compact verical-external-cavity surface-emitting- laser exhibiting a high beam quality. We took advantage of thermal lens-based stability to develop a short (3-10 mm) plano-plano external cavity without any intracavity filter. The semiconductor structure emitting at 1microm is optically pumped by a 8W commercial 808 nm multimode diode laser at large incidence angle. For heat management purpose the GaAs-based VECSEL membrane was bonded on a SiC substrate. We measured a low divergence quasi-circular TEM00 beam (M2 = 1.2) close to diffraction limit, with a linear light polarization (>30 dB).We simulated the steady state laser beam of this unstable cavity using Fresnel diffraction. The side mode suppression ratio is > 45 dB. The free running laser linewidth is 37 kHz limited by pump induced thermal fluctuations. Thanks to this high-Q external cavity approach, the frequency noise is low and the dynamics is in the relaxation-oscillation-free regime, exhibiting low intensity noise (< 0.1%), with a cutoff frequency approximately 41MHz above which the shot noise level is reached. The key parameters limiting the laser power and coherence are studied. This design/properties can be extended to other wavelengths.

10.
Opt Express ; 17(12): 9503-8, 2009 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-19506597

RESUMEN

We demonstrate high power high efficiency (0:3 W) low noise single frequency operation of a compact extended-cavity surface-emitting-semiconductor-laser exhibiting a continuous tunability over 0:84 THz with high beam quality. We took advantage of thermal lens-based stability to develop a short (< 3 mm) plano-plano external cavity without any intracavity filter. The structure is optically pumped by a 1 W commercial 830 nm multimode diode laser. No heat management was required. We measured a low divergence circular TEM(00) beam at the diffraction limit (M(2) < 1:05) with a linear light polarization (> 37 dB). The side mode suppression ratio is 60 dB. The free running laser linewidth is 850 kHz limited by pump induced thermal fluctuations. Thanks to this high-Q external cavity approach, the frequency noise is low and the dynamics is in the relaxation-oscillation-free regime, exhibiting a low intensity noise, with a cutoff frequency approximately 250 MHz above which the shot noise level is reached. We show that pump properties define the cavity design and laser coherence.


Asunto(s)
Láseres de Semiconductores , Diseño Asistido por Computadora , Diseño de Equipo , Análisis de Falla de Equipo , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
11.
Opt Lett ; 32(11): 1387-9, 2007 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-17546130

RESUMEN

A room-temperature-operating vertical external cavity surface emitting laser is applied around 1550 nm to intracavity laser absorption spectroscopy analyzed by time-resolved Fourier-transform interferometry. At an equivalent path length of 15 km, the high-resolution spectrum of the semiconductor disk laser emission covers 17 nm simultaneously. A noise-equivalent absorption coefficient at 1 s averaging equal to 1.5 x 10(-10) cm(-1)Hz(-1/2) per spectral element is reported for 65 km, the longest path length employed.

12.
Opt Express ; 15(15): 9403-17, 2007 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-19547287

RESUMEN

We present an experimental and theoretical investigation of the non-linear multimode dynamics of external-cavity VCSELs emitting at 1 and 2.3mm. We account for the stable single-frequency and linearly polarized emission by these laser sources, even in the presence of quantum noise and non-linear mode interactions originating from Four-Wave-Mixing via population pulsations in the quantum-wells. This fact is a consequence of the mode antiphase dynamics. Thanks to the high-Q external cavity configuration, the laser dynamics fall into the oscillation-relaxation-free class-A regime. The characteristic time to achieve single mode emission is ~ 1ms for a 15mm long cavity with an antireflection coated structure and no spectral filter, as for an "ideal" homogeneous gain laser. The side mode suppression ratio is as high as 40 dB, close to the quantum limit. The laser linewidth is at the quantum limit, and is ~ 1Hz at 1mW output. An experimental value <20 kHz has been established. Under standard conditions, without spectral filtering, the optimum cavity length for highly coherent single mode operation is expected in the range 5 to 30mm. Finally, for cavity lengths typically shorter than 5mm, we rather have an "ideal" homogeneous gain class-B laser, exhibiting oscillation-relaxation of the intensity in the 0.1GHz range. These properties contrast with the intrinsic strongly non-linear dynamics of conventional semiconductor lasers.

13.
Am J Physiol ; 276(5): H1520-6, 1999 05.
Artículo en Inglés | MEDLINE | ID: mdl-10330234

RESUMEN

A major function of insulin in target tissues is the activation of glycogen synthase. Phosphatidylinositol 3-kinase (PI3K) has been implicated in the insulin-induced activation of glycogen synthase, although the true function of this enzyme remains unclear. Data presented here demonstrate that the PI3K inhibitors wortmannin and LY-294002 block the insulin-stimulated activation of protein phosphatase 1 (PP1) in rat ventricular cardiomyocytes. This loss of phosphatase activation mimics that seen in diabetic cardiomyocytes, in which insulin stimulation fails to activate both PP1 and glycogen synthase. Interestingly, in diabetic cells, insulin stimulated PI3K activity to 300% of that in untreated controls, whereas this activity was increased by only 77% in normal cells. PI3K protein levels, however, were similar in normal and diabetic cells. Our results indicate that PI3K is involved in the stimulation of glycogen synthase activity by insulin through the regulation of PP1. The inability of insulin to stimulate phosphatase activity in diabetic cells, despite a significant increase in PI3K activity, suggests a defect in the insulin signaling pathway that contributes to the pathology of insulin-dependent diabetes.


Asunto(s)
Androstadienos/farmacología , Inhibidores Enzimáticos/farmacología , Hipoglucemiantes/farmacología , Insulina/farmacología , Miocardio/enzimología , Fosfoproteínas Fosfatasas/metabolismo , Animales , Células Cultivadas , Cromatografía Líquida de Alta Presión , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Activación Enzimática/efectos de los fármacos , Glucógeno/metabolismo , Glucógeno Sintasa-D Fosfatasa/metabolismo , Masculino , Fibras Musculares Esqueléticas/efectos de los fármacos , Fibras Musculares Esqueléticas/enzimología , Miocardio/citología , Fosfatidilinositol 3-Quinasas/análisis , Fosfatidilinositol 3-Quinasas/metabolismo , Proteína Fosfatasa 1 , Ratas , Ratas Sprague-Dawley , Transducción de Señal/fisiología , Wortmanina
14.
Opt Lett ; 24(12): 826-8, 1999 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-18073867

RESUMEN

We report the demonstration of high-sensitivity intracavity laser absorption spectroscopy with multiple-quantum-well vertical-external-cavity surface-emitting semiconductor lasers (VECSEL's). A detection limit of 3 x 10(-10) cm (-1) has been achieved. The spectrotemporal dynamics of a VECSEL in the 1030-nm wavelength region has been studied. The laser was operating cw at room temperature, with a baseline signal-to-noise ratio as high as 400. The laser was optically pumped with a threshold as low as 80 mW and was broadly tunable over a spectral range of approximately 75 nm .

15.
J Cell Physiol ; 166(1): 208-16, 1996 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-8557769

RESUMEN

When 3-4-week-old rats (young rats) are used as a source of hepatocytes, primary culture cells express the adult, differentiated, liver-specific isoform of glycogen synthase. Synthase enzyme protein levels are relatively stable over a 3 day culture period in young but not in adult (> 150 g rat) hepatocyte cultures. Corresponding synthase enzyme activity and mRNA levels decrease over time in culture in adult but not in young hepatocyte cultures. Young rat hepatocytes also have the ability to proliferate in chemically defined medium in the absence of added mitogens. A diabetes-induced increase in total synthase activity has been demonstrated by our lab and others, using cultured hepatocytes, liver homogenates, and perfused livers. In the present study, utilizing synthase-specific antibody and primary cultures of cells from young normal and alloxan diabetic rats, we found that greater total synthase activity in the diabetic cells was associated with higher levels of enzyme protein. Immuneprecipitation of 35S methionine-labeled freshly plated cells demonstrates an increase in the rate of protein synthesis in diabetic as compared with normal cells. Synthase mRNA levels are correspondingly increased in the diabetic relative to normal cells. Chronic exposure of young, normal hepatocytes to increasing levels of glucose induces a dose-dependent increase in total synthase activity, total synthase protein, and synthase message levels. By comparison, cells from diabetic animals do not respond by any of these measures to increased glucose concentrations. We conclude that this defined primary culture system represents a useful model for investigating the regulation of hepatic glycogen synthase and the defects which occur as a result of diabetes.


Asunto(s)
Diabetes Mellitus Experimental/enzimología , Glucógeno Sintasa/metabolismo , Hígado/citología , Factores de Edad , Aloxano/farmacología , Animales , Animales Recién Nacidos , Especificidad de Anticuerpos , Western Blotting , División Celular/fisiología , Células Cultivadas/citología , Células Cultivadas/enzimología , Medios de Cultivo , Relación Dosis-Respuesta a Droga , Glucosa/farmacología , Glucógeno Sintasa/genética , Glucógeno Sintasa/inmunología , Hígado/enzimología , Mitógenos/farmacología , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Ribonucleasas
16.
J Mol Cell Cardiol ; 25(10): 1171-8, 1993 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-8263951

RESUMEN

The ability of insulin, IGF-1 and IGF-2 to stimulate the activation of glycogen synthase in the heart was compared under completely defined conditions using primary culture cardiomyocytes. Both insulin and IGF-1 produced similar time- and concentration-dependent activation of glycogen synthase with the maximum stimulation observed at 10-15 min following hormone administration and at > or = 10 nM insulin or IGF-1. IGF-2 was largely ineffective at physiological concentrations. When primary culture cardiomyocytes were incubated with 100 microM palmitate for 2 h and then challenged with various concentrations of insulin or IGF-1, there was a significant decrease in the ability of the cells to activate glycogen synthase. In addition, maintaining cardiomyocytes in hormone deficient culture conditions for 24 or 48 h also resulted in a reduced ability to activate glycogen synthase in response to these hormones. These results suggest that (1) both insulin and IGF-1 are potent regulators of glycogen synthesis in the heart, (2) the enzymes involved in the dephosphorylation (activation) of glycogen synthase are closely linked to both insulin and IGF-1, but not IGF-2 receptor signaling pathways, (3) glycogen synthase activation is adversely affected by the maintenance of cardiomyocytes in the presence of palmitate or for > or = 24 h in hormone deficient media which results in insulin and IGF-1 resistance, and (4) this resistance, like that found in cells from diabetic rats, is due at least in part to a decrease in glycogen synthase phosphatase activity.


Asunto(s)
Glucógeno Sintasa/metabolismo , Miocardio/enzimología , Animales , Células Cultivadas , Diabetes Mellitus Experimental/enzimología , Activación Enzimática , Insulina/fisiología , Resistencia a la Insulina , Factor I del Crecimiento Similar a la Insulina/fisiología , Factor II del Crecimiento Similar a la Insulina/fisiología , Miocardio/citología , Ratas , Ratas Sprague-Dawley , Factores de Tiempo
17.
Am J Physiol ; 257(1 Pt 1): E74-80, 1989 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-2665520

RESUMEN

Whereas total cardiac glycogen phosphorylase activity appears to be unaffected by severe insulin deficiency, a diabetes-induced decreased in hepatic glycogen phosphorylase activity has been demonstrated by our laboratory and others using liver extracts, isolated perfused liver, and cultured hepatocytes. The loss of activity in diabetic liver can be correlated with a drop in protein levels. Using primary cultures of cells from normal and diabetic rats and phosphorylase specific antibodies, we found a corresponding decrease in phosphorylase synthesis in diabetic hepatocytes cultured for 2 days in a serum-free, chemically defined medium. When hepatocytes are cultured in the presence of insulin, triiodothyronine, and cortisol, there is a significant recovery in the rate of phosphorylase synthesis after 3 days. Over the 3-day time period, there is no significant difference in the rate of phosphorylase degradation in normal compared with diabetic hepatocytes. Total protein synthesis in both hepatocytes and cardiomyocytes is unaffected by diabetes, as is phosphorylase synthesis in cultured cardiomyocytes.


Asunto(s)
Diabetes Mellitus Experimental/metabolismo , Hígado/enzimología , Miocardio/enzimología , Fosforilasas/biosíntesis , Animales , Western Blotting , Células Cultivadas , Electroforesis en Gel de Poliacrilamida , Hidrocortisona/farmacología , Técnicas de Inmunoadsorción , Insulina/farmacología , Cinética , Hígado/efectos de los fármacos , Masculino , Biosíntesis de Proteínas , Ratas , Ratas Endogámicas , Triyodotironina/farmacología
18.
J Biol Chem ; 262(9): 4000-6, 1987 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-3104335

RESUMEN

Defective acute regulation of hepatic glycogen synthase by glucose and insulin, caused by severe insulin deficiency, can be corrected in adult rat hepatocytes in primary culture by inclusion of insulin, triiodothyronine, and cortisol in a chemically defined serum-free culture medium over a 3-day period (Miller, T. B., Jr., Garnache, A. K., Cruz, J., McPherson, R. K., and Wolleben, C. (1986) J. Biol. Chem. 261, 785-790). Using primary cultures of hepatocytes isolated from normal and diabetic rats in the same serum-free chemically defined medium, the present study addresses the effects of cycloheximide and actinomycin D on the chronic actions of insulin, triiodothyronine, and cortisol to facilitate the direct effects of glucose on the short-term activation of glycogen synthase. The short-term presence (1 h) of the protein synthesis blockers had no effect on acute activation of glycogen synthase by glucose in primary hepatocyte cultures from normal rats. Normal cells maintained in the presence of cycloheximide or actinomycin D for 2 and 3 days exhibited unimpaired responsiveness to glucose activation of synthase. The protein synthesis inhibitors were effective at blocking the restoration of glucose activation of synthase in diabetic cells in media which restored the activation in their absence. Restoration of glycogen synthase phosphatase activity by insulin, triiodothyronine, and cortisol in primary cultures of diabetic hepatocytes was also blocked by cycloheximide or actinomycin D. These data clearly demonstrate that restoration of acute glycogen synthase activation by glucose and restoration of glycogen synthase phosphatase activity in primary cultures of hepatocytes from adult diabetic rats are dependent upon the synthesis of new protein.


Asunto(s)
Diabetes Mellitus Experimental/enzimología , Glucosa/farmacología , Glucógeno Sintasa/metabolismo , Hígado/enzimología , Biosíntesis de Proteínas , Animales , Células Cultivadas , Cicloheximida/farmacología , Dactinomicina/farmacología , Activación Enzimática/efectos de los fármacos , Glucógeno/metabolismo , Glucógeno Sintasa-D Fosfatasa/metabolismo , Hidrocortisona/farmacología , Insulina/farmacología , Hígado/efectos de los fármacos , Masculino , Ratas , Ratas Endogámicas , Triyodotironina/farmacología
19.
J Biol Chem ; 261(2): 785-90, 1986 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-3079760

RESUMEN

Defects in the deposition of glycogen and the regulation of glycogen synthesis in the livers of severely insulin-deficient rats can be reversed, in vivo, within hours of insulin administration. Using primary cultures of hepatocytes isolated from normal and diabetic rats in a serum-free chemically defined medium, the present study addresses the chronic action of insulin to facilitate the direct effects of insulin and glucose on the short term regulation of the enzymes controlling glycogen metabolism. Primary cultures were maintained in the presence of insulin, triiodothyronine, and cortisol for 1-3 days. On day 1 in alloxan diabetic cultures, 10(-7) M insulin did not acutely activate glycogen synthase over a period of 15 min or 1 h, whereas insulin acutely activated synthase in cultures of normal hepatocytes. By day 3 in hepatocytes isolated from alloxan diabetic rats, insulin effected an approximate 30% increase in per cent synthase I within 15 min as was also the case for normal cells. The acute effect of insulin on synthase activation was independent of changes in phosphorylase alpha. Whereas glycogen synthase phosphatase activity could not be shown to be acutely affected by insulin, the total activity in diabetic cells was restored to normal control values over the 3-day culture period. The acute effect of 30 mM glucose to activate glycogen synthase in cultured hepatocytes from normal rats after 1 day of culture was missing in hepatocytes isolated from either alloxan or spontaneously diabetic (BB/W) rats. After 3 days in culture, glucose produced a 50% increase in glycogen synthase activity during a 10-min period under the same conditions. These studies clearly demonstrate that insulin acts in a chronic manner in concert with thyroid hormones and steroids to facilitate acute regulation of hepatic glycogen synthesis by both insulin and glucose.


Asunto(s)
Diabetes Mellitus Experimental/metabolismo , Glucosa/farmacología , Insulina/farmacología , Glucógeno Hepático/metabolismo , Animales , Activación Enzimática , Glucógeno Sintasa/metabolismo , Glucógeno Sintasa-D Fosfatasa/metabolismo , Hígado/efectos de los fármacos , Masculino , Ratas , Ratas Endogámicas , Factores de Tiempo
20.
J Biol Chem ; 259(20): 12470-4, 1984 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-6092334

RESUMEN

Activation of glycogen synthase in the perfused rat liver is defective in severely diabetic rats. In the present study, activation of glycogen synthase by glucose and increased incorporation of [14C]glucose into glycogen by insulin are defective in hepatocytes isolated from alloxan diabetic rats. Acute activation of glycogen synthase in hepatocytes isolated from diabetic rats was restored by treatment of the rats with insulin in vivo. Restoration of synthase activation was not achieved by incubation of hepatocytes in the presence of insulin in vitro for up to 12 h. When isolated hepatocytes from diabetic rats were placed in primary culture in a serum-free defined medium over a 3-day period, glycogen synthesis was partially restored by cortisol and triiodothyronine and dramatically increased by insulin. Concomitant with restoration of [14C]glycogen synthesis was an insulin-mediated increase in glycogen synthase I and synthase phosphatase activity. Restoration of regulation of glycogen synthesis in primary cultures of hepatocytes from diabetic rats by insulin required the presence of cortisol and triiodothyronine. Primary cultures of hepatocytes from normal rats did not require triiodothyronine for insulin to effect glycogenesis over a 3-day period. These data demonstrate that insulin acts in a chronic manner in concert with other hormones to control synthase phosphatase activity, an effect which may be influencing acute control of hepatic glycogen synthesis.


Asunto(s)
Diabetes Mellitus Experimental/enzimología , Glucógeno Sintasa-D Fosfatasa/metabolismo , Insulina/farmacología , Hígado/enzimología , Fosfoproteínas Fosfatasas/metabolismo , Animales , Células Cultivadas , Activación Enzimática , Glucosa/farmacología , Cinética , Hígado/efectos de los fármacos , Glucógeno Hepático/biosíntesis , Masculino , Ratas , Ratas Endogámicas
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