PubMed Health⌕ Search

Biomedical subjects

Jun Ren

Publications and source records attributed to Jun Ren.

At least 163 records · Page 9Linked to original sources
PubMed2003

[Dynamics of urease activity in a long-term fertilized black soil and its affecting factors].

The effect of long-term fertilization on the urease activity in a typical black soil in Northeastern China was examined in this paper. The soil has been fertilized since 1980, and the dynamics of its urease activity was monitored during crop growth season. The results showed that a significant difference in soil urease activity was found at each growth stage between soils treated by different fertilizations. In farmyard manure treated soil, the urease activity was > 160 mg.kg-1.h-1 and with a low seasonal fluctuations. The soil urease activity had a significant positive correlation with soil biological, physical and chemical properties, and the N, P and K contents in plants (P < 0.01), and with soil moisture content and grain crude protein (P < 0.05).

Fertilizers↗
PubMed2003

[Studies of microsatellite isolation from porcine PAC clone].

A novel microsatellite DNA was isolated from a single porcine PAC clone by sequencing the PAC clone directly with (CA)n repeat motif anchored primer. The specific primer pairs flanking the (CA)n repeat region were used to amplify the genomic DNA of 40 individuals from 8 pig breeds, which detected three alleles with the fragment length of 305 bp, 307 bp and 309 bp. The PCR product sequencing results of homozygous animals representing three alleles revealed that those three alleles contained 12,13 and 14 CA dinucleotide repeats respectively.

English Abstract↗
PubMed2002

A distinct physiological state of Lactococcus lactis cells that confers survival against a direct and prolonged exposure to severe stresses.

When exponential phase cultures of Lactococcus lactis were directly exposed to severe stresses (acid, bile salt, heat, and hydrogen peroxide) for a prolonged period, most of the cells were quickly killed, however, a small number of the cells, approximately 0.01% of the population, was found to survive. How these 'survivor' cells might have survived the stresses, when other supposedly-the-same cells could not, was investigated. The cultures were not exposed to any mild stresses prior to the exposure to the severe stresses, and therefore adaptation can be ruled out as the cause of survival. When the survivor cells were re-cultured and re-exposed to the same severe stresses a similar pattern of survival was displayed, indicating that the survivor cells were not stress-resistant mutants. Furthermore, the survivor cells displayed typical growth kinetics once they were freed of the stresses. The survivor cells appear to be in a distinct physiological state, because when they were tested against a second stress they exhibited significantly greater survival against that stress than the normal cells exposed to the same stress. Also, cells at different time points of synchronously growing culture displayed different levels of survival against stress. It is proposed that the difference in survival of exponential phase cells is due to the difference in the protein makeup of cells at different stages of the cell cycle.

Acids↗
PubMed2002

Ca2+ channel blocking effect of iso-S-petasin in rat aortic smooth muscle cells.

The purpose of the present study was to examine the mechanisms underlying the putative hypotensive actions of iso-S-petasin, a sesquiterpene extract of Petasites formosanus through both in vivo and in vitro experiments. Intravenous administration of iso-S-petasin elicited dose-dependent (0.1-1.5 mg/kg) hypotensive and bradycardiac responses in anesthetized rats. Isometric tension recording in isolated thoracic aorta revealed that iso-S-petasin (0.01-100 microM) inhibited KCl- or Bay K 8644 (1,4-dihydro-2,6-dimethyl-5-nitro-4-[2'-(trifluoromethyl)phenyl]-3-pyridinecarboxylic acid methyl ester)-induced vasoconstriction independent of endothelium. Iso-S-Petasin also attenuated Ca(2+)-induced vasoconstriction in a concentration-dependent manner in Ca(2+)-depleted/high K(+)-depolarized ring segments, indicating that iso-S-petasin inhibited Ca(2+) influx into vascular smooth muscle cells. This was confirmed by whole-cell patch-clamp recording in cultured vascular smooth muscle cells where iso-S-petasin (10-100 microM) appeared to directly inhibit the L-type voltage-dependent Ca(2+) channel (VDCC) activity. Intracellular Ca(2+) concentration ([Ca(2+)](i)) measurements using the fluorescent probe fura-2/AM (1-[2-(5-carboxyoxazol-2-yl)-6-aminobenzofuran-5-oxy]-2-(2'-amino-5'-methylphenoxy)-ethane-N,N,N',N'-tetraacetic acid pentaacetoxymethyl ester) showed suppression of the KCl-stimulated increase in [Ca(2+)](i) by iso-S-petasin (10, 100 microM). In conclusion, these results suggest that Ca(2+) antagonism of the L-type VDCC in vascular smooth muscle cells might largely account for the hypotensive action of iso-S-petasin.

Animals↗
PubMed2002

Dietary Mg(2+) supplementation restores impaired vasoactive responses in isolated rat aorta induced by chronic ethanol consumption.

Chronic ethanol consumption contributes to cardiovascular dysfunction possibly related to loss of Mg(2+). This study was designed to examine the role of dietary Mg(2+) supplementation on chronic ethanol ingestion-induced vascular alteration. Rats were fed an ethanol liquid diet supplemented with or without Mg(2+) for 12 weeks. The force-generating capacity was examined in thoracic aortic rings. Ethanol-consuming animals exhibited significantly elevated blood pressure. In aorta with intact endothelium, the contractile responses to norepinephrine and KCl were greatly attenuated and potentiated, respectively. Interestingly, the ethanol-induced alterations in blood pressure and vasoconstrictive response were restored by Mg(2+) supplementation. Pretreatment with the beta(1)-adrenoceptor antagonist atenolol in intact aortic rings abolished the difference in response to norepinephrine between the control and ethanol groups, which implies the involvement of a weakened beta(1)-adrenoceptor component in vessels from the ethanol-fed rats. The norepinephrine-induced vasoconstriction in intact aorta rings was completely abolished by the alpha(1)-adrenoceptor antagonist prazosin. In endothelium-denuded aorta, the contractile response to norepinephrine or KCl was not significantly different between the ethanol and Mg(2+) groups. Endothelium-dependent vasorelaxation to carbamylcholine chloride was not altered by either ethanol or Mg(2+) supplementation. Sodium nitroprusside-induced vasorelaxation was depressed by ethanol, and restored by Mg(2+), in aorta with or without endothelium. These data suggest that chronic ethanol consumption contributes to alterations of endothelium-dependent and -independent vascular response. These alterations can be compensated by dietary Mg(2+) supplementation.

Animals↗
PubMed2002

Anisodamine inhibits cardiac contraction and intracellular Ca(2+) transients in isolated adult rat ventricular myocytes.

Increased cardiac workload often leads to serious complications during cardiac surgery such as pericardiopulmonary bypass. Various agents have been applied to lower peripheral resistance and cardiac workload, one of which, anisodamine, is widely used in Asia. However, the direct action of anisodamine on cardiac contractile property is essentially unknown. This study was designed to examine the influence of anisodamine on ventricular contractile function at the single cardiac myocyte level. Ventricular myocytes from adult rat hearts were stimulated to contract at 0.5 Hz, and mechanical and intracellular Ca(2+) properties were evaluated using an IonOptix Myocam system. Contractile properties analyzed included peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR(90)), maximal velocity of shortening/relengthening (+/-dL/dt), intracellular Ca(2+) fluorescence intensity change (DeltaFFI) and decay (tau). Anisodamine exhibited a concentration-dependent (10(-12)-10(-6) M) inhibition in PS and DeltaFFI, with maximal inhibitions of 44.7% and 47.2%, respectively. Anisodamine inhibited +/-dL/dt, lowered resting FFI but elicited no effect on TPS/TR(90) and tau. Pretreatment with the nitric oxide synthase (NOS) inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 microM) abolished the inhibitory effect of anisodamine in cell shortening. In addition, anisodamine prevented cholinoceptor agonist carbachol-induced positive cardiac contractile response. This study demonstrated a direct cardiac depressive action of anisodamine at the myocyte level, which may be related to, at least in part, NO production and cholinoceptor antagonism.

Animals↗
PubMed2002

Chemical coding and electrophysiology of enteric neurons expressing neurofilament 145 in guinea pig gastrointestinal tract.

Electrophysiologic recording and indirect immunofluorescence were combined to study localization of the medium-sized neurofilament 145 (NF145) component of the cytoskeleton in morphologically identified neurons in the myenteric and submucosal plexuses of the guinea pig enteric nervous system. Neuronal localization of chemical markers, including calbindin DK28, calretinin, nitric oxide synthase, choline-acetyltransferase, neuropeptide Y, serotonin, neurokinin 1 receptor protein, and somatostatin, was integrated with electrophysiologic and morphologic results for a more complete assessment. NF145 immunoreactivity (-IR) was present in ganglion cells with Dogiel type I morphology in the myenteric plexus of the stomach and small and large intestine. NF145-IR was not found in myenteric ganglion cells with Dogiel type II morphology. NF145-IR was not present in any of the ganglion cells in the submucosal plexus. NF145 was expressed in nerve fibers in both myenteric and submucosal plexuses. The majority of these fibers were identified as sympathetic postganglionic axons based on their disappearance in organotypic culture and on their expression of tyrosine hydroxylase. The myenteric ganglion cells with NF145-IR had electrophysiologic properties of S-type enteric neurons. NF145-IR was found in neurons with vasoactive intestinal peptide, serotonin, nitric oxide synthase, somatostatin, and neurokinin 1 receptor but not with neuropeptide Y or calbindin. The results in general suggest that NF145 is localized to distinct subsets of myenteric motor neurons and interneurons. Absence of NF145 from ganglion cells in the submucosal plexus is an example of differences between myenteric and submucosal components of the enteric nervous system.

Action Potentials↗
PubMed2002

Influence of hypertension on acetaldehyde-induced vasorelaxation in rat thoracic aorta.

Ethanol causes vasoconstriction and contributes to the development of hypertension. Acetaldehyde (ACA), the primary metabolite of ethanol, elevates blood pressure by releasing endogenous catecholamines. In vitro, ACA leads to vasorelaxation, although the response may vary among various vascular beds. This study examined the influence of hypertensive state on the ACA-induced vasorelaxant responsiveness. Ring segments of thoracic aorta were isolated from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) and isometric tension development was measured. In aorta with or without intact endothelium, the contractile responses to KCl and norepinephrine were greatly attenuated, whereas vasoconstrictive response to 5-HT was enhanced, by hypertension. Vasorelaxant response to histamine was similar between WKY and SHR groups. ACA (1-30 mM) elicited endothelium-intact as well as -denuded vasorelaxation in a dose-dependent manner in aorta from both WKY and SHR groups. Interestingly, the ACA-induced endothelium-intact vasorelaxation was significantly diminished, whereas the ACA-induced endothelium-denuded vasorelaxation was significantly augmented, by hypertension. These data indicated that the ACA-induced vasorelaxant response, either endothelium-intact or-denuded, is altered by the hypertensive state.

Acetaldehyde↗
PubMed2002

Prediabetic insulin resistance is not permissive to the development of cardiac resistance to insulin-like growth factor I in ventricular myocytes.

Resistance to insulin-like growth factor I (IGF-1)-induced cardiac contractile response has been reported in diabetes. To evaluate the role of prediabetic insulin resistance to cardiac IGF-1 resistance, whole body insulin resistance was generated with dietary sucrose and contractile function was evaluated in ventricular myocytes. Mechanical properties were evaluated using an IonOptix system and intracellular Ca(2+) transients were measured as changes in fura-2 fluorescence intensity (Delta FFI). After 8 weeks of feeding, sucrose rats displayed euglycemia, hepatomeglay and normal heart size, and glucose intolerance, confirming the presence of insulin resistance. Myocytes from sucrose-fed rats displayed decreased peak shortening (PS), reduced resting FFI, increased intracellular Ca(2+) clearing, associated with normal duration of shortening and relengthening compared to myocytes from starch-fed rats. IGF-1 (10(-10)-10(-6) M) caused a similar concentration-dependent decrease in PS in both groups. Only the highest concentration of IGF-1 elicited an inhibition on Delta FFI in sucrose myocytes. In addition, the IGF-1-induced response was abolished by the IGF-1 receptor antagonist H-1356 in both groups, and by the nitric oxide synthase inhibitor L-NAME in starch but not sucrose myocytes. These results indicated prediabetic insulin resistance alters cardiac contractile function at the myocytes level, but may not be permissive to cardiac contractile resistance to IGF-1.

Animals↗
PubMed2002

Influence of prenatal ethanol exposure on vascular contractile response in rat thoracic aorta.

Fetal alcohol syndrome is associated with cardiovascular malformation. However, the impact of prenatal ethanol exposure on vascular function is not clear. The purpose of this study was to examine the influence of prenatal ethanol exposure on vascular response in adulthood. Timed-pregnancy, female rats were fed an ethanol-containing liquid diet (36% calorically or 6.36% [vol./vol.]) or control diet from gestation day 2 until labor. The pups continued to receive a standard rat chow through adulthood, and the force-generating capacity of aortic ring segments was examined. Prenatal ethanol exposure did not significantly affect postnatal growth, but it did lead to elevated blood pressure in adulthood. The contractile response to potassium chloride was similar in vessels with intact endothelium, although the median effective concentration (EC(50)) was significantly reduced by prenatal ethanol exposure in rings with denuded endothelium. The response to norepinephrine was attenuated by prenatal ethanol exposure in rings with either intact or denuded endothelium. The endothelium-dependent relaxation to carbamylcholine chloride was significantly attenuated by prenatal ethanol exposure. Vasorelaxant response to the nitric oxide donor sodium nitroprusside or beta-adrenergic agonist isoproterenol was similar between control and prenatal-ethanol-exposed groups with either intact or denuded endothelium. Ethanol elicited a dose-dependent endothelium-dependent vasorelaxation, which was comparable between the two animal groups. The ethanol-induced endothelium-dependent vasorelaxation was attenuated by the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester. These findings seem to indicate that prenatal ethanol exposure contributes to alterations of both endothelium-dependent and endothelium-independent vascular contractile responses.

Animals↗
PubMed2002

Comparison of cardiac excitation-contraction coupling in isolated ventricular myocytes between rat and mouse.

Transgenic animals offer many advantages for physiological study. The mouse is the most extensively utilized mammalian model for gene modification. Isolated ventricular myocytes are pivotal for assessment of cardiac function by allowing direct cellular and environmental manipulation without interference from compensatory mechanisms that may exist in vivo. This study was designed to compare the basic excitation-contraction coupling properties of mouse and rat ventricular myocytes. Cardiac myocytes were isolated from age- and gender-matched mice (FVB and C57BL/6) and rats (Sprague-Dawley (SD) and Wistar). Mechanical and intracellular Ca2+ properties were measured with an IonOptix SoftEdge system, including peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR(90)), maximal velocity of shortening and relengthening (+/-dL/dt), and intracellular Ca2+ fura-2 fluorescence intensity and decay rate (tau). Resting cell length was variable among the different species or strains. PS from FVB group was significantly higher than the SD group. TPS and TR(90) were significantly shorter in mice. +dL/dt was similar among all groups whereas -dL/dt was significantly faster in the C57BL/6 group compared to the rat groups. Resting intracellular Ca2+ was lower in mice than in rats, and Ca2+-induced Ca2+ release was variable among the four groups. Intracellular Ca2+ decay was slower in Wistar compared to all other groups. The myocytes from C57BL/6 did not respond to increases in extracellular Ca2+. Myocytes from the FVB group exhibited a lesser reduction in PS in response to elevated stimulus frequency. These data suggest that inherent differences between strains or species should be taken into consideration when comparing results from these different animal models.

Animals↗
PubMed2002

Short-term administration of insulin-like growth factor I (IGF-1) does not induce myocardial IGF-1 resistance.

The advent of recombinant technology has revealed attractive therapeutic profile of insulin-like growth factor I (IGF-1) in the treatment of chronic cardiovascular diseases such as diabetes and heart failure. However, the safety and potential adverse effect of IGF-1 have not been well defined. This study was designed to evaluate the impact of short-term IGF-1 administration on myocardial contractile function. Adult rats were given recombinant human IGF-1 (3mg/kg/d, s.c.) for 8 weeks. Mechanical properties were evaluated in left-ventricular papillary muscles using a force-transducer. Myocardial contractile properties analyzed included peak tension development (PTD), time-to-peak tension (TPT), time-to-90% relaxation (RT(90)), and maximal velocity of tension development/decline (+/-VT). Short-term IGF-1 treatment enhanced the plasma IGF-1 level but had no effect on body and organ weights. The myocardium from IGF-1-treated rats exhibited enhanced PTD associated with similar TPT, RT(90), and +/-VT compared to the control group. IGF-1-treated myocardium exhibits an enhanced PTD-Ca(2+) response and a better intracellular Ca(2+) replenishing ability at the low stimulus frequencies. Acute application of IGF-1 (1-500 ng/ml) elicited a comparable concentration-dependent increase in PTD in myocardium from both control and the IGF-1-treated groups. Acute IGF-1 application had no effect on +/-VT, TPT, and RT(90) in either group tested. Pretreatment with the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester blunted the IGF-1-induced positive response in myocardium from both control and IGF-1-treated groups. These results suggest that short-term IGF-1 treatment is unlikely to induce IGF-1 resistance in myocardial contractile function.

Animals↗
PubMed2002

Norepinephrine regulates the in vivo expression of the L-type calcium channel.

The alpha1c subunit (DHP receptor) of the L-type Ca2+ channel is important for calcium homeostasis in cardiac muscle. The DHPr provides the primary mechanism for calcium influx during contraction. Published results demonstrate three in vitro signaling pathways that are important in the regulation of DHPr gene expression in neonatal cardiac myocytes, the protein kinase A (PKA), protein kinase C (PKC) pathways, and intracellular calcium. To determine whether these pathways are important in vivo, we treated adult rats with infusions of isoproterenol, or norepinephrine at 200 microg/kg/h and assessed DHPr mRNA and protein levels. Following a 3-day infusion isoproterenol (ISO) and norepinephrine (NE) produced a small but insignificant reduction in DHPr mRNA levels. When the infusions were continued for 7 days isoproterenol increased DHPr mRNA accumulation to control levels while NE stimulated a 35% increase in DHPr mRNA levels and a 35% increase in protein abundance when compared to controls (p < 0.05). Furthermore, contractility and Ca2+ transient measurements of isolated cardiac myocytes from NE infused animals also display shortened duration of contraction/relaxation and increased intracellular free Ca2+ (DFFI) in response to electrical stimulation (p < 0.01). We conclude norepinephrine treatment alters DHPr mRNA and protein levels, and augments excitation-contraction coupling, and thus may be important for modulating cardiac calcium homeostasis in vivo.

Animals↗
PubMed2002

Impaired cardiac excitation-contraction coupling in ventricular myocytes from Ames dwarf mice with IGF-I deficiency.

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are involved in the regulation of cardiovascular function. GH/IGF-I deficiency is associated with impaired cardiac performance manifested as reduced left ventricular ejection fraction and diastolic filling. This study was to determine the impact of IGF-I deficiency on single cardiac myocyte excitation-contraction (E-C) coupling. Ventricular myocytes were isolated from adult Ames dwarf mice and age-matched wild-type siblings. Dwarf mice are characterized by severe IGF-I deficiency. Mechanical properties were evaluated using a video edge detection system. Myocytes were electrically stimulated at 0.5 Hz. The contractile properties analysed included peak shortening (PS), time to peak shortening (TPS) and time to 90% relengthening (TR(90)), and maximal velocities of shortening/relengthening (+/-d L/d t). Intracellular Ca(2+) transients were evaluated by fura-2 fluorescence microscopy. Dwarf mice exhibited significantly reduced body and heart weights and severely deficient plasma IGF-I. Myocytes from dwarf mice displayed significantly smaller cell lengths (CLs), prolonged TPS/TR(90) and reduced +/-d L/d t compared with the wild-type littermates. The absolute PS was similar although PS/CL was enhanced in the dwarf group. Myocytes from dwarf animals displayed reduced peak intracellular Ca(2+) levels and slowed intracellular Ca(2+) clearing associated with a comparable resting intracellular Ca(2+). Furthermore, myocytes from the dwarf hearts were equally responsive to an elevation in extracellular Ca(2+) and exhibited an augmented stepwise decrease in response to minimal increase in stimulating frequencies compared with those from the wild-type group. These results suggest that deficiency in IGF-I may be directly associated with cardiac E-C coupling dysfunction at the ventricular myocyte level.

Animals↗
PubMed2002

Sepsis-induced depressed contractile function of isolated ventricular myocytes is due to altered calcium transient properties.

Chronic peritoneal sepsis in a rodent model produces myocardial dysfunction characterized by decreased rates of ventricular contraction and relaxation in the isolated heart preparation. However, it remains controversial whether the ventricular contractility is altered during sepsis. In the present study, we determined the effect of chronic peritoneal sepsis on the mechanical properties and intracellular Ca2+ handling of cardiac myocytes isolated from septic rats at 24 or 48 h. Mechanical properties were evaluated by use of an IonOptix MyoCam system. Myocytes were electrically stimulated at 0.5 Hz. The contractile properties analyzed included peak shortening (PS), time-to-peak shortening (TPS), time-to-90% relengthening (TR90), and maximal velocities of shortening and relengthening (+/-dL/dt). Intracellular Ca2+ handling was evaluated with fura-2 fluorescent dye. Myocytes obtained from 24-h postseptic animals exhibited a depressed PS (85% of control), normal TPS, prolonged TR90 (147% of control), and reduced +/-dL/dt (both 79% of control). Myocytes from 48-h postseptic animals also exhibited a reduced peak of intracellular Ca2+ sequestration (55% of control), but resting intracellular Ca2+ and Ca2+-transient decay were comparable with the values seen in myocytes from untreated rats. Myocytes from septic and control animals were equally responsive over a range of stimulation frequencies (0.1-5 Hz). Myocytes from septic animals were unresponsive (5% of control) to increase of extracellular Ca2+ (0.5-3 mM). These results demonstrate that sepsis produces substantial deficits in cardiac myocytes function that can be attributed to altered calcium transient properties.

Animals↗
PubMed2002

Influence of genetically predisposed diabetes on ethanol-induced depression of cardiac contraction in adult rat ventricular myocytes.

Diabetes mellitus and alcohol (ethanol) intake are two positively correlated major risk factors for cardiovascular abnormalities. However, the interaction of the two on cardiac function is largely unknown. The purpose of the present study was to examine the impact of genetically predisposed diabetes on acute ethanol exposure-induced cardiac contractile depression at the myocyte level. Ventricular myocytes from spontaneously biobreeding diabetes-prone (BBDP) rats and their diabetes-resistant littermates (BBDR) were stimulated to contract at 0.5 Hz. Contractile properties analysed include: peak shortening amplitude (PS), time-to-PS (TPS), time-to-90 % relengthening (TR(90)) and maximal velocities of shortening/relengthening (+/- dL/dt). BBDP rats displayed hyperglycaemia, reduced body weight gain and increased cardiac, hepatic and renal size. Myocytes isolated from BBDP rat hearts exhibited prolonged TPS and TR(90) associated with normal PS and +/- dL/dt, compared with myocytes from the BBDR group. Acute ethanol exposure (80-640 mg dl(-1)) caused a concentration-dependent inhibition of PS in both BBDR and BBDP myocytes. However, the degree of inhibition of PS was significantly reduced in BBDP myocytes compared to that of BBDR myocytes. The maximal inhibition was 52.9 % and 28.4 % in BBDR and BBDP groups, respectively. Ethanol significantly depressed +/- dL/dt in both BBDR and BBDP myocytes. In addition, ethanol did not affect TPS or TR(90) in either the BBDR or BBDP group. Collectively, these results suggest that the ethanol-induced depression in cardiac myocyte contraction may be 'shadowed' by genetically predisposed diabetes.

Actin Cytoskeleton↗
PubMed2002

IGF-I attenuates diabetes-induced cardiac contractile dysfunction in ventricular myocytes.

Diabetic cardiomyopathy is characterized by impaired ventricular contraction and altered function of insulin-like growth factor I (IGF-I), a key factor for cardiac growth and function. Endogenous IGF-I has been shown to alleviate diabetic cardiomyopathy. This study was designed to evaluate exogenous IGF-I treatment on the development of diabetic cardiomyopathy. Adult rats were divided into four groups: control, control + IGF-I, diabetic, and diabetic + IGF-I. Streptozotocin (STZ; 55 mg/kg) was used to induce experimental diabetes immediately followed by a 7-wk IGF-I (3 mg. kg(-1). day(-1) ip) treatment. Mechanical properties were assessed in ventricular myocytes including peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR(90)) and maximal velocities of shortening/relengthening (+/-dL/dt). Intracellular Ca(2+) transients were evaluated as Ca(2+)-induced Ca(2+) release and Ca(2+) clearing constant. Levels of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA), phospholamban (PLB), and glucose transporter (GLUT4) were assessed by Western blot. STZ caused significant weight loss and elevated blood glucose, demonstrating the diabetic status. The diabetic state is associated with reduced serum IGF-I levels, which were restored by IGF-I treatment. Diabetic myocytes showed reduced PS and +/-dL/dt as well as prolonged TPS, TR(90), and intracellular Ca(2+) clearing compared with control. IGF-I treatment prevented the diabetes-induced abnormalities in PS, +/-dL/dt, TR(90), and Ca(2+) clearing but not TPS. The levels of SERCA and GLUT4, but not PLB, were significantly reduced in diabetic hearts compared with controls. IGF-I treatment restored the diabetes-induced decline in SERCA, whereas it had no effect on GLUT4 and PLB levels. These results suggest that exogenous IGF-I treatment may ameliorate contractile disturbances in cardiomyocytes from diabetic animals and could provide therapeutic potential in the treatment of diabetic cardiomyopathy.

Animals↗