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

Streptozotocin-induced diabetes reduced cellular lipoprotein lipase (LPL) activity in cardiac myocytes from rat hearts and decreased the heparin-induced release of LPL into the medium. This effect of diabetes was rapidly reversed by in vivo treatment with insulin (5 U iv for 1 h); administration of insulin in vivo to control rats also increased heparin-releasable LPL activity. In contrast, in vitro addition of insulin to control and diabetic myocytes did not alter either cellular or heparin-releasable LPL activities. Insulin stimulated glucose oxidation and protein synthesis in control and diabetic myocytes. Decavanadate (0.05-1 mM) or vanadyl ion (0.5 mM) enhanced the release of LPL into the medium. Heparin- and decavanadate-induced release of LPL was not additive, and heparin pretreatment reduced the subsequent release of LPL by decavanadate. Decavanadate displaced LPL bound to heparin-Sepharose and increased LPL release into the perfusate of hearts. Therefore, decavanadate can mimic heparin in its effect on LPL. The absence of a direct in vitro effect of insulin on LPL in cardiac myocytes suggests that insulin may require some other in vivo factor or that diabetes-induced changes in LPL activity are secondary to some other metabolic factor.
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PMID:Lipoprotein lipase release from cardiac myocytes is increased by decavanadate but not insulin. 159 Mar 76

A major complication of diabetes mellitus is retinopathy, which is characterized by increased neovascularization and neuronal degeneration in the retina. The biochemical processes underlying these changes are largely unknown. To better understand the role(s) of insulin or its lack and the resultant hyperglycemia in the etiology of these events, peripheral and neuronal (having 125 kDa and 115 kDa alpha subunits, respectively) insulin receptor subtype levels in the retinas of Streptozocin-induced diabetic rats were quantified. Immunoblot analysis of wheat germ agglutinin-agarose purified retinal membrane proteins revealed that retinas from diabetic rats expressed higher insulin receptor levels than retinas from control rats. This increase reflected a doubling of neuronal and a approximately 20% decrease in peripheral insulin receptor subtypes, respectively. Insulin-treated diabetic rats had neuronal receptor levels equal to control values, at the same time having a further reduced number of peripheral insulin receptors relative to controls. Affinity labeling analysis of WGA-purified retinal membrane proteins indicated a 1.5-fold increase in neuronal and a 9% decrease in peripheral receptor subtypes, corroborating the immunoblot analysis. Neuronal insulin receptors in WGA-purified cortical synaptosomal membranes also were increased in diabetic rats, with insulin treatment reducing this effect. The up-regulated receptors retained their ability to undergo insulin-dependent autophosphorylation and, as such, did not appear functionally impaired. These data suggest that the expression of neuronal insulin receptors in retina and brain and peripheral insulin receptors in the retina of diabetic rats is sensitive to levels of insulin/glucose in peripheral circulation.
Diabetes 1992 Jul
PMID:Differential expression of retinal insulin receptors in STZ-induced diabetic rats. 161 96

The effects of Zn2+ in mimicking insulin in vivo and in vitro are further characterized. Like insulin, Zn2+ stimulated the conversion of [U-14C]-, [1-14C]-, and [6-14C]glucose to lipids in rat adipocytes. Maximum stimulation of lipogenesis was 55-80% of maximum insulin response after preincubation (30 min at 37 degrees C) of adipocytes with ZnCl2 (0.4 mM). Under these conditions, the half-maximum effect was achieved at 0.17 +/- 0.02 mM of ZnCl2. Similarly, an insulinlike effect of Zn2+ was observed on the oxidation of glucose by both pathways, glycolytic and hexose monophosphate shunt. In contrast, unlike insulin, Zn2+ did not inhibit lipolysis but rather exhibited a slight lipolytic activity. Also, the effect of Zn2+ on hexose influx did not exceed 14 +/- 3% that of insulin. The stimulatory effects of Zn2+ were not related to generation of H2O2. Catalase (100 micrograms/ml) did not inhibit Zn(2+)-stimulated glucose oxidation and its incorporation into lipids. Zn2+ had an additive effect on either insulin- or vanadate-stimulated conversion of [1-14C]glucose to fat, and together, the effect was approximately 140% of the maximum rate of lipogenesis. Chelation of intracellular Zn2+ by the cell-permeable chelator N,N,N',N'-tetrakis (2-pyridylmethyl)ethylenediamine did not significantly affect the ability of insulin to stimulate lipogenesis. Adipocytes derived from STZ rats were largely refractory to the modulating action of insulin. In contrast, the effect of Zn2+ on lipogenesis in these cells was more pronounced.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1992 Aug
PMID:Insulinlike effects of zinc ion in vitro and in vivo. Preferential effects on desensitized adipocytes and induction of normoglycemia in streptozocin-induced rats. 162 74

Zinc-calcium-phosphorous oxide (ZCAP) ceramics were developed to deliver insulin in vivo in rats. Thirty-nine Sprague-Dawley male albino rats (Holtzman Co., Madison, WI), weighing 260 +/- 15 g each, were randomly distributed into six groups: normal controls (3), sham controls (3), diabetic controls (6) and three diabetic experimental groups each consisting of nine rats. Diabetes was induced in rats by an intravenous injection of Streptozotocin (75 mg/kg body weight). Rats in the three diabetic experimental groups were implanted subcutaneously with two ZCAP capsules, each containing 10, 15, or 20 mg of insulin. Blood glucose measurements were taken at least twice a week over a six week period. Plasma insulin levels were measured at two, four, and six weeks by a radioimmunoassay using 125I labeled insulin. Normoglycemia was maintained for three weeks in rats implanted with ZCAP capsules containing a total of 20 mg of insulin. Plasma insulin levels correlated with the normal blood glucose levels in these rats. Thus, ZCAP capsules could be used to deliver insulin and maintain normoglycemia in diabetic rats.
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PMID:Insulin delivery by zinc calcium phosphate ceramics. 164 23

The contribution of hormone-stimulated glycogenolysis to hepatic glucose production was studied in hepatocytes from streptozotocin diabetic rats. To this end, the activation of glycogen phosphorylase by glucagon, vasopressin, and the alpha 1-adrenergic agonist phenylephrine was compared in hepatocytes from normal and diabetic rats and related to glycogen content, glucose production, and microsomal glucose-6-phosphatase activity. Streptozotocin-induced diabetes reduced the glycogen content and the amount of total (a + b) phosphorylase in hepatocytes proportionally to the severity of the disease. In cells from severely diabetic rats (group 1), the responsiveness of activation of phosphorylase to the hormones was reduced by about half, consistent with a 45% reduction in total phosphorylase. In addition, the sensitivity of phosphorylase activation to all hormones investigated was decreased by about 1 order of magnitude or more in cells of this group. In hepatocytes from rats with milder diabetes (group 2), maximal phosphorylase activation reached an intermediate value between that of the control group and of group 1. In response to all hormones investigated, group 2 diabetic rat hepatocytes produced less glucose than control rat liver cells, while in group 1 there was no increase in glucose production at all, presumably because glycogen concentration was too low. However, in group 2 diabetic rat hepatocytes, glucagon-stimulated glucose production, unlike phosphorylase activation, did not show decrease sensitivity, presumably because glucose-6-phosphatase activity is increased by diabetes. Our results thus indicate that hormone-stimulated liver glycogenolysis is unlikely to contribute to enhanced glucose production in insulin-deficient diabetes, despite increased glucose-6-phosphatase activity.
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PMID:Hormone-stimulated glucose production from glycogen in hepatocytes from streptozotocin diabetic rats. 165 43

Streptozotocin (STZ)-induced diabetes in the rat causes a significant reduction in ouabain-sensitive Na,K-ATPase pumping activity measured by 86Rb+ influx, in sciatic endoneurium (by 54%) and dorsal root ganglia (by 22%). For endoneurium, the change is similar to that of ouabain-sensitive enzymatic Na,K-ATPase activity (42%), but in dorsal root ganglia, the decrease in enzymatic Na,K-ATPase activity was much greater. 86Rb+ efflux from dorsal root ganglia showed no difference between diabetic and control animals, confirming that the abnormal 86Rb+ influx reflects Na,K-ATPase function and not abnormal membrane permeability. The significance of these findings to pathogenetic mechanisms in diabetic neuropathy is discussed.
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PMID:Rubidium (86Rb+) influx into dorsal root ganglia and sciatic nerve endoneurium of control and streptozotocin-diabetic rats: comparison with enzymatic Na,K-ATPase activity. 165 45

The effects of long-term high-fiber diet on lipid and glucose levels and the histological changes in the coronary arteries and thoracic aorta in STZ-induced diabetic SD rats were investigated. During the first 4 weeks of the study period, all diabetic rats were given regular chow plus water after which, all were grouped according to the following diet regimen: group II, no added cholesterol and glucomannan; group III, no added cholesterol but with glucomannan supplement, group IV, with added cholesterol but no glucomannan supplement; and group V, with both cholesterol and glucomannan supplements. 15% weight of glucomannan and 1.5% weight of cholesterol in regular rat chow were used as supplements when indicated. Non-diabetic rats which received only regular chow served as the control group (group I). In the 18th week all rats were sacrificed and weight gain, glucose, total cholesterol, HDL-cholesterol, triglyceride and lipid peroxidase concentrations were determined. Selected portions of the heart and thoracic aorta were histologically examined. Weight gain was higher in rats supplemented with glucomannan than in those without glucomannan supplements, but the difference is not significant. A lowering tendency in glucose levels was likewise observed. Furthermore, total cholesterol and HDL-cholesterol levels were lower and higher, respectively in diabetic rats receiving glucomannan. Although the triglyceride levels were similar in all rats, lipid peroxidase levels were significantly lower in rats with high-fiber diet.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res Clin Pract 1991 Sep
PMID:Effects of long-term high-fiber diet on macrovascular changes and lipid and glucose levels in STZ-induced diabetic SD rats. 165 79

Insulin receptor tyrosine kinase activity solubilized from hind limb muscle of control and streptozocin-induced diabetic (STZ-D) rats (2-3 wk) was studied with the substrates histone H2B and poly glutamic acid-tyrosine (glu-tyr) (4:1). Basal and insulin-stimulated kinase activities were inhibited when high concentrations of either substrate were added before initiation of phosphorylation with ATP. Under these conditions, insulin-stimulated activities of diabetic- and control-derived receptor kinase toward H2B were similar at 0.008 mg/ml H2B. However, higher concentrations of H2B (0.04-1 mg/ml) progressively reduced the ratios of diabetic-derived to control-derived receptor kinase activities to approximately 0.5. When inhibition of receptor kinase activities was prevented by allowing maximal autophosphorylation of insulin receptors before addition of H2B, kinase activity of diabetic- and control-derived receptors was similar at all H2B concentrations. Diabetic-derived insulin-receptor tyrosine kinase activity toward poly glu-tyr (4:1) was not significantly different from that of control rats. Under conditions of substrate inhibition (0.4 mg/ml H2B), insulin receptor H2B kinase activity from muscles of rats with severe diabetes (85 mg/kg STZ, 7 days) was significantly decreased, whereas the same activity from rats with moderate diabetes (50 mg/kg STZ, 7 days) was not significantly different from control rats. Insulin receptor alpha,beta dimers were not detectable in muscle preparations from control or diabetic rats. The data suggest that the impairment of muscle-derived insulin-receptor tyrosine kinase activity associated with insulinopenic diabetes reflects, in part, enhanced inhibition by some substrates. If solubilized insulin receptors and the exogenous substrates studied model in vivo events, impaired signaling of the muscle insulin receptor in insulinopenic diabetes may depend on the type and concentration of intracellular tyrosine kinase substrates and the severity of the metabolic derangements.
Diabetes 1991 Dec
PMID:Skeletal muscle insulin-receptor kinase. Effects of substrate inhibition and diabetes. 166 94

1. Measurements were made, relative to tissue DNA, of the activities of enzymes of glycerolipid synthesis in homogenates of interscapular brown adipose tissue. These were: mitochondrial and microsomal forms of glycerolphosphate acyltransferase (GPAT), Mg(2+)-dependent phosphatidate phosphohydrolase (PPH) and fatty acyl-CoA synthetase (FAS). 2. In normal animals, 3 days of cold-exposure (4 degrees C) increased all activities. The increase in mitochondrial GPAT activity was particularly pronounced (5-fold). Administration of the beta-adrenergic agonist BRL 26830A mimicked the effect of cold on microsomal GPAT activity. Mitochondrial GPAT, PPH and FAS activities were unresponsive to BRL 26830A. The alpha-adrenergic agonist phenylephrine significantly decreased activities of GPAT and PPH. 3. Streptozotocin-diabetes decreased mitochondrial GPAT activity, but did not abolish the effect of cold to increase this activity or the activity of microsomal GPAT. Diabetes abolished the effect of cold on PPH and FAS activities. 4. The findings are relevant to signals that drive early events in mitochondriogenesis and cell proliferation in brown adipose tissue on exposure to cold.
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PMID:Activities of enzymes of glycerolipid synthesis in brown adipose tissue after treatment of rats with the adrenergic agonists BRL 26830A and phenylephrine, after exposure to cold and in streptozotocin-diabetes. 167 97

The influence of diabetes on the gonadotropin response to the negative feedback effect of testosterone (T) and hypothalamic neurotransmitter turnover rates in adult male rats was evaluated. Adult male Sprague-Dawley rats were made diabetic by an intraperitoneal injection of streptozotocin (STZ; 5 mg/100 g body weight) in citrate buffer. Vehicle-injected rats served as controls. On day 9, all rats were bilaterally castrated and treated subcutaneously on alternate days with either peanut oil or T propionate (TP) in peanut oil (100 micrograms/rat). Plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and T concentrations were measured by specific radioimmunoassays from blood samples collected on day 1 (before castration) and 2, 4, 6, and 7 days after castration. On day 7 after castration (day 15 after vehicle or STZ treatment), 1 h before autopsy, the rats were injected intraperitoneally with saline or a tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine (25 mg/100 g BW), for the measurement of norepinephrine (NE) and dopamine turnover in median eminence and medial basal hypothalamus (MBH). Circulating FSH, LH, PRL, and T levels were significantly lower (FSH and T: p less than 0.001; LH and PRL: p less than 0.05) in gonad-intact rats treated with STZ than in vehicle-injected animals. The castration-induced increase in plasma LH levels was attenuated in diabetic rats. The suppressive effect of T on LH secretion was significantly greater (p less than 0.001) in STZ-treated rats relative to TP-treated nondiabetic controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of diabetes on the gonadotropin response to the negative feedback effect of testosterone and hypothalamic neurotransmitter turnover in adult male rats. 168 39


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