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

Changes in the activities of 6-phosphofructo-1-kinase (PFK, EC 2.7.1.11) in the placenta and jejunal mucosa of pregnant rats during the onset of experimental diabetes induced by streptozotocin were investigated. The concentrations of fructose 2,6-bisphosphate were significantly decreased in the placenta and small intestine of the streptozotocin-induced diabetic rats. The total activities and the activity ratios (activity at 0.5 mM fructose 6-phosphate at pH 7.0/activity at pH 8.0 (v0.5/V] of placental and jejunal PFK of diabetic pregnant and virgin rats were markedly diminished as compared to normal control rats. Also the susceptibility of jejunal and placental PFK to inhibition by ATP was increased in the diabetic virgin and pregnant rats. Administration of insulin in vivo completely reversed the effects of diabetes on the regulatory properties and on the total activities of placental and jejunal PFK. It is suggested that the diminished activity of PFK in the placenta and small intestine of streptozotocin-induced diabetic rats could be the result of the decreased concentrations of fructose 2,6-bisphosphate as well as the effect of insulin on the activity of PFK.
Diabetes Res Clin Pract 1991 Aug
PMID:Regulation of 6-phosphofructo-1-kinase in the placenta and small intestine of pregnant streptozotocin-induced diabetic rats. 183 74

Insulin receptor tyrosine kinase activity solubilized from liver of control and streptozotocin diabetic rats was studied using histone H2b and poly-Glu-Tyr (4:1) as phosphoacceptors. Both substrates inhibited autophosphorylation and exogenous kinase activity when added before, but not after, receptor activation with ATP. When H2b was added before ATP, insulin stimulated exogenous kinase activity of diabetic-derived receptors was significantly higher (approximately 50%) than control values at low H2b concentrations, but significantly lower (approximately 50%) than control values at high H2b concentrations, suggesting a decrease in the apparent Km and maximal velocity of the diabetic receptor tyrosine kinase toward H2b. When receptors were allowed to maximally autophosphorylate before the addition of H2b, the maximal H2b kinase activity of diabetic-derived receptors was only approximately 25% lower than that of controls. These effects were not attributable to altered ATP kinetics. Insulin receptor kinase activity toward the substrate poly-Glu-Tyr (4:1) was unaltered by insulinopenic diabetes. Insulin receptor alpha-beta dimers were not detectable in either control or diabetic-derived preparations. We conclude that the impairment of hepatic insulin receptor kinase activity associated with insulinopenic diabetes reflects a decreased ability to maximally activate, which is enhanced when the receptor is activated in the presence of some substrates, e.g. H2b. Impaired signalling by the diabetic-derived receptor appears to be dependent on the type of substrate and its concentration.
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PMID:Diabetes-associated impairment of hepatic insulin receptor tyrosine kinase activity: a study of mechanisms. 184 1

Urinary bladder function was examined in the spontaneously diabetic BB rat six months after the onset of diabetes. Diabetes caused significant decreases in rat weight and increases in bladder body weights and in vivo bladder capacities compared to age-matched controls, but no changes in the weights of bladder bases. The absolute contractile responses of urinary bladder body and base strips to nerve stimulation, carbachol, 5-hydroxytryptamine, ATP, phenylephrine, and KCl were unaltered by diabetes. However, when the data were corrected for tissue mass, there were slight but not significant decreases in contractile responses of strips from diabetic rats. There were increases in total muscarinic receptor numbers and calcium channel binding sites in bladder bodies from BB rats as a result of the increases in tissue mass. The data indicate that the six month-diabetic BB rat differs from the streptozotocin-diabetic rat in the sensitivity of the urinary bladder to the complications of diabetes, probably as a result of the insulin treatment required to keep BB rats alive.
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PMID:Urinary bladder function 6 months after the onset of diabetes in the spontaneously diabetic BB rat. 184 33

This study was designed to determine if the known decrease in slow axonal transport of proteins in the sciatic nerve of experimentally diabetic rats is related to altered phosphorylation of neurofilament proteins (NFPs). Rats were rendered diabetic with 50 mg/kg of streptozotocin, i.p. At 3 and 6 weeks later, NFPs were prepared from spinal cord. The in vivo phosphorylation state of NFPs was examined by using phosphate-dependent (RT97) and -independent (RMd09) antibodies against high-molecular-mass NFPs on Western blots. Neurofilament-associated kinase activity was also measured in vitro by incubation of NFPs with [32P]ATP. Phosphorylation of all three NFPs (high, medium, and low molecular mass) occurred, as confirmed by gel electrophoresis and autoradiography. At 30 min of incubation, protein-bound radioactivity in NFPs from diabetic animals was reduced to 86.7 +/- 3.4 and 54.3 +/- 19.6% of that in nondiabetic animals at 3 and 6 weeks of diabetes, respectively (p less than 0.001 and p less than 0.05, respectively). NFPs were also incubated with acid phosphatase and rephosphorylated. Results showed that the increased in vivo phosphorylation contributed to the decreased in vitro phosphorylation. Extraction of protein kinases and addition back to the NFPs revealed, in addition, a reduced activity in the diabetic animals of the protein kinases measured in vitro.
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PMID:Neurofilament protein phosphorylation in spinal cord of experimentally diabetic rats. 184 79

Sarcolemmal membranes were isolated from skeletal muscle by a sucrose density gradient method from rats with diabetes induced by a streptozotocin injection (65 mg/kg iv). The activities of Na(+)-dependent Ca2+ uptake and Ca2(+)-stimulated adenosine-triphosphatase (ATPase) in the sarcolemmal fraction from diabetic rats was higher than those from the control animals. These changes were apparent at various times of incubation (1-10 min) as well as at different concentrations of free Ca2+ (10(-7) to 10(-5) M) and developed during the third and/or fourth weeks after streptozotocin injection. ATP-dependent Ca2+ uptake in the sarcolemmal vesicles was also increased at 28 and 56 days after inducing diabetes. Treatment of diabetic animals with insulin for 14 days reversed the changes in Ca2+ transport activities toward the control levels. Sarcolemmal Mg2(+)-ATPase and Na(+)-K(+)-ATPase activities remained unchanged in diabetic preparations. Furthermore, no difference in the sarcolemmal phospholipid composition and sodium dodecyl sulfate-gel electrophoretic pattern was evident between the control and experimental groups. These results indicate a higher activity of the sarcolemmal Ca2+ transport, which may be associated with hyperfunction of the skeletal muscle in diabetic rats.
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PMID:Increased sarcolemmal Ca2+ transport activity in skeletal muscle of diabetic rats. 185 Feb 3

Micturition characteristics and in vitro urinary bladder function were investigated in insulin-treated spontaneously diabetic BB rats and age-matched non-diabetic controls one year after the onset of diabetes. BB rats weighed less than controls and were hyperglycemic. Diabetic rats consumed larger volumes of water and excreted larger volumes of urine than controls. The frequency of micturitions and the mean volumes of urine excreted per micturition were significantly increased in BB rats compared to age-matched controls. Associated with the micturition changes in the BB rats were significant increases in bladder body mass. Contractile responses of strips from bladder bodies and bases were measured in response to nerve stimulation, carbachol, phenylephrine, ATP, and KCl. No significant differences between controls and diabetics were found in the absolute contractile responses of bladder body strips to nerve stimulation, carbachol, ATP, or KCl. However, if the data were transformed to correct for the increases in tissue mass in the diabetics, there were significant decreases in the responses of bladder body strips from BB rats to carbachol, ATP, and KCl, but not to nerve stimulation. Even after transformation, there were no differences in the responses of bladder base strips to carbachol, phenylephrine, or KCl. The data indicate that significant changes in micturition characteristics are evident one year after the onset of diabetes in the spontaneously diabetic BB rat. These changes are slow in development, since they are absent six months after the onset of diabetes. The changes in micturition and bladder strip contractility are qualitatively similar to, but quantitatively modest in comparison with those caused by streptozotocin-induced diabetes mellitus. The quantitative differences are probably attributable to an ameliorative effect of the insulin received by the BB rat.
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PMID:Changes in bladder function in the one year spontaneously diabetic BB rat. 185 57

Sulphonylureas such as glibenclamide, which are used in the treatment of Type-2 diabetes, are inhibitors of ATP-sensitive potassium channels. These channels link cellular metabolism to membrane electrical activity and it is likely that they are closely associated with glibenclamide binding sites. Quantitative autoradiography was used to localize high-affinity [3H]glibenclamide binding sites in coronal sections of rat brain. The relative density of binding sites was found to correlate well with the relative capacity of sites determined in homogenate assays. There was no evidence of any variation of affinity between brain regions. The highest levels of binding were found in the substantia nigra with high levels in the globus pallidus, cerebral cortex, hippocampus and caudate-putamen, intermediate levels in the cerebellum, and low levels in the hypothalamus and pons. The density of [3H]glibenclamide binding sites was low in glucose-responsive brain regions, known to contain ATP-sensitive potassium channels that are inhibited by sulphonylureas. However, higher densities were associated with brain regions (often limbic structures) active during temporal lobe epilepsy. In at least two of these structures, the CA3 region of the hippocampus and the substantia nigra, it is probable that these sites are coupled to ATP-sensitive potassium channels. These results are discussed with reference to the reported actions of ATP-sensitive potassium channels on CNS function.
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PMID:The regional distribution of sulphonylurea binding sites in rat brain. 190 17

The effect of Ca2+ and calmodulin on phosphorylation of islet secretory granule proteins was studied. Secretory granules were incubated in a phosphorylation reaction mixture containing [32P]ATP and test reagents. The 32P-labeled proteins were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the 32P content was visualized by autoradiography, and the relative intensities of specific bands were quantitated. When the reaction mixture contained EGTA and no added Ca2+, 32P was incorporated into two proteins with molecular weights of 45,000 and 13,000. When 10(-4) M Ca2+ was added without EGTA, two additional proteins (58,000 and 48,000 Mr) were phosphorylated, and the 13,000-Mr protein was absent. The addition of 2.4 microM calmodulin markedly enhanced the phosphorylation of the 58,000- and 48,000-Mr proteins and resulted in the phosphorylation of a major protein whose molecular weight (64,000 Mr) is identical to that of one of the calmodulin binding proteins located on the granule surface. Calmodulin had no effect on phosphorylation in the absence of Ca2+ but was effective in the presence of calcium between 10 nM and 50 microM. Trifluoperazine and calmidazolium, calmodulin antagonists, produced a dose-dependent inhibition of the calmodulin effect. 12-O-tetradecanoylphorbol 13-acetate, a phorbol ester that activates protein kinase C, produced no increase in phosphorylation, and 1-(5-isoquinoline sulfonyl)-2-methyl piperazine dihydrochloride, an inhibitor of protein kinase C, had no effect. These results indicate that Ca(2+)-calmodulin-dependent protein kinases and endogenous substrates are present in islet secretory granules.
Diabetes 1991 Aug
PMID:Ca(2+)-calmodulin-dependent phosphorylation of islet secretory granule proteins. 190 48

It is well established that cardiac dysfunction independent of atherosclerosis develops in both humans and animals with diabetes mellitus. The etiology is complex, involving many different processes, one of which may be increased fatty acid utilization and/or a concomitant decrease in glucose utilization by the diabetic heart. We compared control and 6-wk streptozotocin (STZ)-induced diabetic isolated working rat hearts and were able to demonstrate cardiac dysfunction in the diabetic as assessed by depressed heart rate (HR), heart rate peak systolic pressure product (HR.PSP), left ventricular developed pressure (LVDP), and rate of pressure rise (+dP/dt). Paralleling depressed cardiac function in the diabetic were hyperglycemia, hyperlipidemia, and decreased body weight gain compared with age-matched controls. The addition of free fatty acids, in the form of 1.2 mM palmitate, to the isolated working heart perfusate had no effect on either control or diabetic heart function, with the exception of a depressive effect on +dP/dt of diabetic hearts. But diabetic hearts perfused with palmitate-containing perfusate plus the glucose oxidation stimulator dichloroacetate (DCA) showed a marked improvement in function. HR and HR.PSP in spontaneously beating hearts, as well as LVDP and +dP/dt in paced hearts were all restored to control heart values in diabetic hearts perfused in the presence of DCA. Creatine phosphate and ATP levels were similar under all perfusion conditions, thus eliminating energy stores as the limiting factor in heart function. Results indicate that DCA will acutely reverse diabetic cardiac function depression. Therefore glucose oxidation depression in the diabetic heart may be a significant factor contributing to cardiac dysfunction.
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PMID:Effects of free fatty acids and dichloroacetate on isolated working diabetic rat heart. 192 88

Changes in high-energy phosphate content and cardiac contractile function of isolated rat hearts as well as changes in Ca2+ sensitivity and mitochondrial respiration of myocardial skinned fibers were assessed in hereditary cardiomyopathies and in cardiomyopathies induced by chronic treatment with adriamycin or norepinephrine, by autoimmunization, by diabetes, or by creatine deficiency. The sum of ATP and phosphocreatine contents as well as cardiac output at standard load conditions was substantially lower in almost all groups. The common features of cardiac pump failure were mild bradycardia, elevated left ventricular (LV) diastolic pressure, and stiffness that limited cardiac contractile adaptation to volume or resistance loads. The LV diastolic stiffness at maximal functional load was inversely correlated with high-energy phosphate content. Increased myofibrillar sensitivity to Ca2+ and defective function of mitochondrial creatine kinase were found in skinned myocardial fibers. These results suggested that both increased myofibrillar Ca2+ sensitivity and energy deficiency within myofibrils may contribute to increased myocardial stiffness. Increased stiffness limits LV filling but facilitates pressure development, which partly compensates for decreased contractility of cardiomyopathic hearts.
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PMID:Energy-linked functional alterations in experimental cardiomyopathies. 192 52


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