Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The biguanide, metformin, is widely used for the treatment of type 2 diabetes mellitus. In the recently published United Kingdom Prospective Diabetes Study (UKPDS), it was shown that the use of metformin was associated with a reduction of macrovascular complications compared to other blood glucose-lowering strategies. The present study was aimed at determining whether metformin has direct beneficial effects on the heart. We tested the effects of metformin on cardiac functional recovery after a mild ischemic incident (stunning) in our isolated, erythrocyte perfused, rat working-heart model. Three groups were tested: vehicle, 50 and 500 micromol/l metformin (total n = 6). In diabetic rats, a concentration of 50 microM has been shown to reduce the blood glucose concentration. Slight metformin-induced increases in coronary blood flow during normoxia (pre-ischemically) and during reperfusion (post-ischemically) were observed and compared to vehicle (p < 0.05). Both metformin concentrations significantly reduced cardiac functional loss induced by the 12-min global ischemic incident compared with vehicle (3.4 +/- 1.0 % and 3.5 +/- 0.6 % loss during metformin versus 10.7 +/- 0.8 % during vehicle, p < 0.001). This study clearly shows that metformin acutely improves cardiac function after a mild ischemic incident (stunning) in rats.
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PMID:Metformin improves cardiac functional recovery after ischemia in rats. 1198 26

A considerable number of experimental, epidemiological and clinical studies are now available which point to an important role of Mg2+ in the etiology of cardiovascular pathology. In human subjects, hypomagnesemia is often associated with an imbalance of electrolytes such as Na+, K+ and Ca2+. Abnormal dietary deficiency of Mg2+ as well as abnormalities in Mg2+ metabolism play important roles in different types of heart diseases such as ischemic heart disease, congestive heart failure, sudden cardiac death, atheroscelerosis, a number of cardiac arrhythmias and ventricular complications in diabetes mellitus. Mg2+ deficiency results in progressive vasoconstriction of the coronary vessels leading to a marked reduction in oxygen and nutrient delivery to the cardiac myocytes. Numerous experimental and clinical data have suggested that Mg2+ deficiency can induce elevation of intracellular Ca2+ concentrations, formation of oxygen radicals, proinflammatory agents and growth factors and changes in membrane perrmeability and transport processes in cardiac cells. The opposing effects of Mg2+ and Ca2+ on myocardial contractility may be due to the competition between Mg2+ and Ca2+ for the same binding sites on key myocardial contractile proteins such as troponin C, myosin and actin. Stimulants, for example, catecholamines can evoke marked Mg2+ efflux which appears to be associated with a concomitant increase in the force of contraction of the heart. It has been suggested that Mg2+ efflux may be linked to the Ca2+ signalling pathway. Depletion of Mg2+ by alcohol in cardiac cells causes an increase in intracellular Ca2+, leading to coronary artery vasospasm, arrhythmias, ischemic damage and cardiac failure. Hypomagnesemia is commonly associated with hypokalemia and occurs in patients with hypertension or myocardial infarction as well as in chronic alcoholism. The inability of the senescent myocardium to respond to ischemic stress could be due to several reasons. Mg2+ supplemented K+ cardioplegia modulates Ca2+ accumulation and is directly involved in the mechanisms leading to enhanced post ischemic functional recovery in the aged myocardium following ischemia. While many of these mechanisms remain controversial and in some cases speculative, the beneficial effects related to consequences of Mg2+ supplementation are apparent. Further research are needed for the incorporation of these findings toward the development of novel myocardial protective role of Mg2+ to reduce morbidity and mortality of patients suffering from a variety of cardiac diseases.
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PMID:Protective role of magnesium in cardiovascular diseases: a review. 1234 4

Forty-three patients with diabetes (47 shoulders) who had a manipulation under anesthesia only (24 shoulders), a manipulation under anesthesia followed by an arthroscopy (12 shoulders), or an arthroscopic release (11 shoulders) for a frozen shoulder were followed-up for a mean period of 35 months. The mean Constant score improved from 20.3 to 63.7 points (P <.001). The mean improvement in forward flexion was 71.7 degrees, in abduction 78.5 degrees, in external rotation with the arm at the side 36.3 degrees, and in internal rotation from the buttock to the first lumbar vertebra (P <.001 for all). When gentle manipulation with the patient under anesthesia was possible, the outcome was satisfactory in 13 of 15 shoulders (86.7%) in patients with non-insulin-dependent diabetes and in 17 of 21 shoulders (81%) in patients with insulin-dependent diabetes (P >.5). Insulin-dependent patients with diabetes were more likely to require an arthroscopic release than patients with non-insulin-dependent diabetes (P <.05). Most of our patients obtained their maximum relief of pain and functional recovery within 3 months of surgery. We recommend manipulation under anesthesia for the resistant frozen shoulder in patients with diabetes. Arthroscopic release is required when mobilization under anesthesia is not possible.
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PMID:Operative management of the frozen shoulder in patients with diabetes. 1246 88

Glucose and palmitate metabolism and contractile function were measured with ex vivo perfused working hearts from control (db/+) and diabetic (db/db) female mice at 6, 10-12, and 16-18 weeks of age. Palmitate oxidation was increased by 2.2-fold in 6-week-old db/db hearts and remained elevated in 10- to 12- and 16- to 18-week-old hearts. Carbohydrate oxidation was normal at 6 weeks but was reduced to 27 and 23% of control at 10-12 and 16-18 weeks, respectively. At 6 weeks, db/db hearts exhibited a slight reduction in mechanical function, whereas marked signs of dysfunction were evident at 10-12 and 16-18 weeks. Mechanical function after ischemia-reperfusion was examined in hearts from male mice; at 6 weeks, db/db hearts showed normal recovery, whereas at 12 weeks it was markedly reduced. Fatty acid oxidation was the predominant substrate used after reperfusion. Thus, diabetic db/db hearts exhibit signs of a progressive cardiomyopathy; increased fatty acid oxidation preceded reductions in carbohydrate oxidation. Postischemic recovery of function was reduced in db/db hearts, in parallel with age-dependent changes in normoxic contractile performance. Finally, peroxisome proliferator-activated receptor-alpha treatment (3 weeks) did not affect sensitivity to ischemia-reperfusion, even though carbohydrate oxidation was increased and palmitate oxidation was decreased.
Diabetes 2003 Feb
PMID:Age-dependent changes in metabolism, contractile function, and ischemic sensitivity in hearts from db/db mice. 1254 Jun 18

Despite dramatic advances in the treatment of acute myocardial infarction (AMI) in recent years, patients with diabetes mellitus continue to experience disproportionately high morbidity and mortality. A substantial body of experimental and clinical data suggest that the ability of the heart to augment its energetic metabolism of glucose in the acute setting is critical to survival and functional recovery after AMI. Emerging evidence also suggests that chronic hyperglycemia may predispose to post-AMI ischemia and heart failure via adverse effects on coronary endothelial function and myocardial ultrastructure, energy metabolism, and gene transcription. A strong case can be made for intensive insulin-based control of glycemic level in the AMI patient with diabetes mellitus.
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PMID:Glucose and insulin management in the post-MI setting. 1264 21

Functional outcome at three months was studied in 72 patients with ischemic stroke. The Canadian Neurological Scale was used to assess the severity of stroke at admission and functional outcome at 3 months was assessed using modified Rankin scale. The size and site of the infarct was noted from the initial CT. Risk factors like hypertension, diabetes, and serum cholesterol were analyzed. Initial neurological scoring at admission, and size and site of the infarct were significantly associated with functional recovery at 3 months.
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PMID:Functional recovery in ischemic stroke. 1474 56

A high rate of myocardial metabolism is needed to generate energy to sustain cardiac contractile activity. Typically, energy generation occurs through the metabolism of free fatty acids (FFAs), glucose, and lactate. However, in individuals who are insulin resistant or who have diabetes mellitus, excessive FFA metabolism occurs in the heart. Pharmacologic manipulation of myocardial metabolism may be beneficial in these patients. There is evidence that the thiazolidinediones (TZDs), aside from exerting insulin-sensitizing effects on fat and skeletal muscles, also act on the myocardium as a result of reducing circulating fatty acid concentrations. Animal studies have shown that the TZDs influence the expression and function of glucose transporters in the heart, leading to improved glucose metabolism. Recent experiments have also shown that administration of TZDs may protect against myocardial injury associated with ischemia and may improve recovery of function during the postischemic period. This article provides a review of the potential beneficial effects of the TZDs on myocardial metabolism.
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PMID:Insulin resistance and the effects of thiazolidinediones on cardiac metabolism. 1467 70

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

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

Neurogenesis after brain injury not only leads to the replacement of damaged cells but might also contribute to functional recovery, suggesting the possibility of endogenous neural repair. We investigated the extent of hippocampal neural regeneration in a rat model of hypoglycemia. Two weeks after 30 min of insulin-induced isoelectric electroencephalogram, extensive neuronal loss was observed in the hippocampus, including area CA1 and dentate gyrus (DG). A transient increase in progenitor cell proliferation in the DG subgranular zone (SGZ) was detected, leading to an increase of immature neuroblasts 1-2 weeks after hypoglycemic insult. Most of the surviving newborn cells assumed a neuronal phenotype within 1 month in DG, a few cells near the site of granule-cell death becoming astroglia or microglia. No neuronal regeneration was observed in the CA1 after hypoglycemia, although dividing cells appeared to be astroglia or microglia in CA1 and dentate hilus. At 4 weeks after hypoglycemia, proliferative activity in the SGZ diminished below baseline in experimental versus control rats, with a subsequent reduction of neuroblasts. Morphological findings (doublecortin staining) suggest permanent progenitor cell loss in some areas of SGZ. Reduced neurogenesis in DG and lack of neuronal regeneration in CA1 may impede cognitive recovery after severe hypoglycemia injury.
Diabetes 2005 Feb
PMID:Hypoglycemia induces transient neurogenesis and subsequent progenitor cell loss in the rat hippocampus. 1567 8


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