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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of streptozotocin (STZ)-induced diabetes (DM) and insulin on cardiac performance were investigated during reperfusion after low-flow ischemia in rats. Hearts were isolated 4 weeks after intravenous injection of STZ (65 mg/kg) or vehicle and retrogradely perfused in the presence (throughout the perfusion period) or absence of 1 U/L insulin using a Langendorff apparatus. Normothermic low-flow global ischemia was instituted by reducing the flow rate to 5% of baseline for 30 min, followed by reperfusion for 30 min. Rate pressure product (left ventricular developed pressure x heart rate) was calculated as an index of cardiac performance. Myocardial concentrations of adenine nucleotides, creatine phosphate (CP) and glycogen were measured. Insulin perfusion increased preischemic myocardial glycogen content in both DM and control hearts. Recovery of cardiac performance and myocardial CP concentrations in the absence of insulin was greater in the DM hearts than in controls during reperfusion. Insulin perfusion improved recovery of cardiac performance and elevated CP concentrations in both DM and control hearts. These results demonstrate greater cardioprotection against ischemia/reperfusion injury in the STZ-DM state and with insulin perfusion. These protective effects may be associated with augmented resynthesis of high-energy phosphates during reperfusion.
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PMID:Cardioprotection by streptozotocin-induced diabetes and insulin against ischemia/reperfusion injury in rats. 1235 10

Cardiovascular disease is one of the most important causes of morbidity and mortality in diabetes mellitus, but there has been controversy over functional impairment of diabetic hearts and their tolerance to ischemia. We studied ischemic heart function in type 2 diabetic rats with different degrees of hyperglycemia and its relationship with cardiac norepinephrine release. Otsuka Long-Evans Tokushima Fatty rats (OLETF) and age-matched Long-Evans Tokushima Otsuka normal rats (LETO) were used. One group of OLETF rats was given 30% sucrose in drinking water (OLETF-S). Hearts were isolated and perfused in a working heart preparation and subjected to 30 min ischemia followed by 40 min reperfusion at age of 12 months. Hemodynamics and coronary norepinephrine overflow were examined. Fasting plasma glucose in OLETF increased markedly at 12 months and sucrose administration exacerbated hyperglycemia in diabetic rats (LETO 6.6 +/- 0.5, OLETF 8.3 +/- 0.7, OLETF-S 15.0 +/- 1.7 mmol/L, P < 0.01). Basic cardiac output in OLETF was decreased as compared with LETO and OLETF-S (LETO 29.4 +/- 2.5, OLETF 24.0 +/- 2.4, OLETF-S 27.0 +/- 0.9 ml/min/g, P < 0.05) and remained very low after ischemia, while in OLETF-S it was well preserved (OLETF 4.2 +/- 2.1, OLETF-S 13.7 +/- 2.6 ml/min/g, P < 0.01). Correspondently, cardiac norepinephrine released during ischemia and reperfusion was lower in OLETF-S (OLETF 2.3 +/- 1.0, OLETF-S 0.7 +/- 0.1 pmol/ml, P < 0.01). Thus, OLETF hearts were more vulnerable to ischemia but sucrose feeding rendered their hearts resistant to ischemia. Less norepinephrine release may play a role in preventing postischemic functional deterioration in sucrose-fed diabetic hearts.
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PMID:Preserved postischemic heart function in sucrose-fed type 2 diabetic OLETF rats. 1269 67

Poor metabolic control resulting from insulin withdrawal in chronic type 1 diabetic rats results in ischemic heart failure. In the present study, we determined whether heart failure occurs in acute type 1 diabetic rats following insulin withdrawal and if prior exercise training can prevent this dysfunction. Four-week-old diabetic prone BB Wor rats were either sedentary or moderately exercised by daily treadmill running. Training was discontinued at the onset of diabetes. Isolated working rat heart function was then assessed in the following groups: diabetic resistant, uncontrolled sedentary diabetic (USD), controlled sedentary diabetic (CSD), uncontrolled trained diabetic (UTD), and controlled trained diabetic (CTD) rats. To induce an uncontrolled state, insulin treatment was withheld for 24 hours. During increased metabolic demand and reperfusion following ischemia, heart rate, contractility, and cardiac output were depressed in hearts from USD animals. Treatment with insulin prevented the depressions in cardiac performance from occurring. Hearts from UTD rats perfused under these conditions showed comparable cardiac function to that seen in the controlled state. This occurred despite poor metabolic control, reflected by elevated levels of plasma glucose and free fatty acids. Our results indicate that metabolic deteriorations in acute diabetes result in ischemic heart failure. However, this cardiac dysfunction can be prevented with exercise training.
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PMID:Prevention of ischemic heart failure by exercise in spontaneously diabetic BB Wor rats subjected to insulin withdrawal. 1280 Jan 8

Sarpogrelate, a specific 5-HT2A receptor antagonist is reported to produce a number of beneficial cardiovascular effects in diabetes mellitus. In the present investigation we have studied the effects of sarpogrelate on 5-HT receptors in heart and platelets in streptozotocin (STZ)-diabetic rats. Diabetes was induced by a single tail vein injection of STZ (45 mg/kg) and sarpogrelate (1 mg/kg, i.p.) was administered daily for 6 weeks. Injection of STZ produced significant loss of body weight, polyphagia, polydypsia, hyperglycemia, hypoinsulinemia, hypertension and bradycardia. Treatment with sarpogrelate significantly lowered fasting glucose levels with corresponding increase in insulin levels. It also significantly prevented STZ-induced polydypsia, hyperphagia, hypertension, and bradycardia but not the loss of body weight. 5-HT produced dose-dependent positive inotropic effect that was found to be decreased significantly in STZ-diabetic rats. Hearts obtained from sarpogrelate treated diabetic rats did not show any decrease in responsiveness to 5-HT. Relative platelet aggregation per se was found to be higher in STZ-diabetic rats as compared to control and this was significantly prevented by sarpogrelate treatment. 5-HT produced a dose-dependent increase in platelet aggregation in non-diabetic and sarpogrelate treated diabetic rats. However, 5-HT failed to produce any increase in platelet aggregation in untreated diabetic rats. Our data suggest that STZ-induced diabetes may produce down-regulation of cardiac 5-HT2A receptors and increased platelet aggregation. Treatment with sarpogrelate seems to prevent STZ-induced down-regulation of 5-HT receptors and increase in platelet activity in diabetic rats.
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PMID:Effect of sarpogrelate on altered STZ-diabetes induced cardiovascular responses to 5-hydroxytryptamine in rats. 1295 98

Alteration in cardiac function is one of the hallmarks of diabetes and in late stage is manifested as a decrease in contractility. While it is established that the release of calcium ions from internal sarcoplasmic reticulum via type 2 ryanodine receptor calcium-release channels (RyR2) is vital for efficient contraction, the relationship between diabetes-induced decrease in cardiac performance and alterations in expression and/or function of RyR2 is not well delineated. The present study was designed to address this question and to determine whether changes to RyR2 induced by chronic diabetes could be minimized with insulin-treatment. When paced at 3.3 Hz (200 beats per minute), hearts from 8-week streptozotocin-induced diabetic rats showed decreased responsiveness to isoproterenol stimulation; +dT/dt and -dT/dt were 56.5 +/- 11.4% and 42.1 +/- 12.1% that of control, respectively. Hearts from 8-week diabetic rats expressed 51.2% less RyR2 than controls, In addition, RyR2 from diabetic rats also showed decreased ability to bind the specific ligand [3H]ryanodine (22.4 +/- 1.8% less [3H]ryanodine per microg of RyR2 protein), suggesting dysfunction. Two-weeks of insulin treatment, initiated after 6 weeks of untreated diabetes was able to minimize loss in function and expression of RyR2. Taken collectively, these data suggest that the decrease in cardiac contractility induced by chronic diabetes results in part from decreases in expression and alteration in function of RyR2 and these changes could be attenuated with insulin treatment.
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PMID:Chronic diabetes alters function and expression of ryanodine receptor calcium-release channels in rat hearts. 1295 6

Vanadium mimicking the metabolic effects of insulin is known to decrease serum glucose levels and to influence glucose metabolism in diabetes mellitus. However, it is unclear whether vanadium ameliorates the metabolic disorder in diabetic hearts causing myocardial dysfunction. The purpose of this study was to assess the effects of vanadium on cardiac performance and energy metabolism in diabetic rat hearts. Four groups of Wistar rats were studied: untreated control rats (group C, n = 8). vanadate-treated rats (group V, n = 10), untreated diabetic rats (group DM, n = 9) induced by streptozotocin. and vanadate-treated diabetic rats (group DMV, n = 8). Vanadate-treated rats drank a 1.5 mM sodium orthovanadate (Na3VO4) solution during a 4 week diabetic condition. Hearts were perfused with Krebs-Henseleit buffer after the diabetic duration. After the maximum left ventricular dP/dt and cardiac efficiency were calculated, the myocardial contents of ATP and creatine phosphate (P-Cr) and myocardial energy metabolism were assessed by cytosolic phosphorylation potential. Peak positive and negative dP/dt, and cardiac efficiency decreased significantly in group DM compared with group C, while there were no significant differences between groups C and DMV. The myocardial contents of ATP (micromol/g wet heart) and P-Cr (micromol/g wet heart), and cytosolic phosphorylation potential (M(-1)) increased from 2.72 +/- 0.46. 1.45 +/- 0.58. and 3,530 +/- 1,220 in group DM to 3.88 +/- 0.76, 3.81 +/- 1.36, and 11,200 +/- 2,400 in group DMV, respectively. It is concluded that vanadium restored the production of high energy phosphates in the myocardium and improved myocardial dysfunction by regulating metabolic processes in diabetic rat hearts.
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PMID:Vanadate improves cardiac function and myocardial energy metabolism in diabetic rat hearts. 1458 56

Lipid accumulation is associated with cardiac dysfunction in diabetes and obesity. Transgenic mice expressing non-transferable lipoprotein lipase (LpL) with a glycosylated phosphatidyl-inositol (GPI) anchor in cardiomyocytes have dilated cardiomyopathy. However, the mechanisms responsible for lipid accumulation and cardiomyopathy are not clear. Hearts from 3-month-old mice expressing GPI-anchored human LpL (hLpLGPI) mice had increased fatty acid oxidation and heart failure genes and decreased glucose transporter genes. 6-month-old mice had increased mRNA expression and activation of the apoptosis marker caspase-3. Moreover, hLpLGPI hearts had significant cytochrome c release from mitochondria to cytosol. Low density lipoprotein uptake was greater in hLpLGPI hearts, and this was associated with more intracellular apolipoprotein B (apoB). To test whether lipid accumulation in the hLpLGPI heart is reduced by cardiac expression of apoB, hLpLGPI mice were bred with transgenic human apoB (HuB)-expressing mice. Hearts of HuB/hLpLGPI mice had less triglyceride (38%) and free fatty acids (19%), secreted more apoB, and expressed less atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) and more glucose transporter 4 (GLUT4). The increased mortality of the mice was abrogated by the transgenic expression of apoB. Therefore, we hypothesize that cardiac apoB expression improves cardiomyopathy by increasing lipid resecretion from the heart.
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PMID:Apolipoprotein B production reduces lipotoxic cardiomyopathy: studies in heart-specific lipoprotein lipase transgenic mouse. 1463 11

The aim of this study was to determine whether the transition from insulin resistance to hyperglycemia in a model of type 2 diabetes leads to intrinsic changes in the myocardium that increase the sensitivity to ischemic injury. Hearts from 6-, 12-, and 24-wk-old lean (Control) and obese Zucker diabetic fatty (ZDF) rats were isolated, perfused, and subjected to 30 min of low-flow ischemia (LFI) and 60 min of reperfusion. At 6 wk, ZDF animals were insulin resistant but not hyperglycemic. By 12 wk, the ZDF group was hyperglycemic and became progressively worse by 24 wk. In spontaneously beating hearts rate-pressure product (RPP) was depressed in the ZDF groups compared with age-matched Controls, primarily due to lower heart rate. Pacing significantly increased RPP in all ZDF groups; however, this was accompanied by a significant decrease in left ventricular developed pressure. There was also greater contracture during LFI in the ZDF groups compared with the Control group; surprisingly, however, functional recovery upon reperfusion was significantly higher in the diabetic 12- and 24-wk ZDF groups compared with age-matched Control groups and the 6-wk ZDF group. This improvement in recovery in the ZDF diabetic groups was independent of substrate availability, severity of ischemia, and duration of diabetes. These data demonstrate that, although the development of type 2 diabetes leads to progressive contractile and metabolic abnormalities during normoxia and LFI, it was not associated with increased susceptibility to ischemic injury.
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PMID:Onset of diabetes in Zucker diabetic fatty (ZDF) rats leads to improved recovery of function after ischemia in the isolated perfused heart. 1472 22

Prolongation of relaxation is a hallmark of diabetic cardiomyopathy. Most studies attribute this defect to decreases in sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2a) expression and SERCA2a-to-phospholamban (PLB) ratio. Since its turnover rate is slow, SERCA2a is susceptible to posttranslational modifications during diabetes. These modifications could in turn compromise conformational rearrangements needed to translocate calcium ions, also leading to a decrease in SERCA2a activity. In the present study one such modification was investigated, namely advanced glycation end products (AGEs). Hearts from 8-week streptozotocin-induced diabetic (8D) rats showed typical slowing in relaxation, confirming cardiomyopathy. Hearts from 8D animals also expressed lower levels of SERCA2a protein and higher levels of PLB. Analysis of matrix-assisted laser desorption/ionization time-of-flight mass data files from trypsin-digested SERCA2a revealed several cytosolic SERCA2a peptides from 8D modified by single noncrosslinking AGEs. Crosslinked AGEs were also found. Lysine residues within actuator and phosphorylation domains were cross-linked to arginine residues within the nucleotide binding domain via pentosidine AGEs. Two weeks of insulin-treatment initiated after 6 weeks of diabetes attenuated these changes. These data demonstrate for the first time that AGEs are formed on SERCA2a during diabetes, suggesting a novel mechanism by which cardiac relaxation can be slowed during diabetes.
Diabetes 2004 Feb
PMID:Diabetes increases formation of advanced glycation end products on Sarco(endo)plasmic reticulum Ca2+-ATPase. 1474 99

Aldose reductase (AR), a member of the aldo-keto reductase family, has been implicated in the development of vascular and neurological complications of diabetes. Recently, we demonstrated that aldose reductase is a component of myocardial ischemic injury and that inhibitors of this enzyme protect rat hearts from ischemia-reperfusion injury. To rigorously test the effect of aldose reductase on myocardial ischemia-reperfusion injury, we used transgenic mice broadly overexpressing human aldose reductase (ARTg) driven by the major histocompatibility complex I promoter. Hearts from these ARTg or littermate mice (WT) (n=6 in each group) were isolated, perfused under normoxic conditions, then subjected to 50 min of severe low flow ischemia followed by 60 min of reperfusion. Creatine kinase (CK) release (a marker of ischemic injury) was measured during reperfusion; left ventricular developed pressure (LVDP), end diastolic pressure (EDP), and ATP were measured throughout the protocol. CK release was significantly greater in ARTg mice compared with the WT mice. LVDP recovery was significantly reduced in ARTg mice compared with the WT mice. Furthermore, ATP content was higher in WT mice compared with ARTg mice during ischemia and reperfusion. Infarct size measured by staining techniques and myocardial damage evaluated histologically were also significantly worse in ARTg mice hearts than in controls. Pharmacological inhibition of aldose reductase significantly reduced ischemic injury and improved functional recovery in ARTg mice. These data strongly support key roles for AR in ischemic injury and impairment of functional and metabolic recovery after ischemia. We propose that interventions targeting AR may provide a novel adjunctive approach to protect ischemic myocardium.
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PMID:Central role for aldose reductase pathway in myocardial ischemic injury. 1528 19


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