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

Twenty rats were made diabetic by treatment with alloxan monohydrate (10% solution, 100 mg/kg body weight). Ten diabetic and ten non-diabetic rats were intraperitoneally infected with the same infective doses of Trypanosoma brucei brucei (Lafia strain). The uninfected controls were ten diabetic and ten non-diabetic rats. The prepatent period was shorter in the diabetics (3.5 +/- 0.5 days) than the non-diabetics (4.2 +/- 0.4 days). Although the infected diabetic and non-diabetic rats had comparable levels of peak parasitaemia, the diabetics had significantly (P < 0.05) higher parasitaemia before this peak. The survival time was shorter (P < 0.05) for the infected diabetics (12.1 +/- 3.2 days) than for the infected non-diabetics (14.8 +/- 1.7 days). The infection did not affect the level of diabetic hyperglycaemia, but caused a more severe anaemia in the diabetics than the non-diabetics, with the percentage decreases in packed cell volume in the diabetics being higher (P < 0.05) from days 3 to 12 post-infection. In conclusion, the pathogenic effects of trypanosome infection may be more severe in rats having alloxan-induced diabetes.
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PMID:Increased severity of acute Trypanosoma brucei brucei infection in rats with alloxan-induced diabetes. 985 Oct 14

The transport of glucose across the blood-brain barrier (BBB) is mediated by the high molecular mass (55-kDa) isoform of the GLUT1 glucose transporter protein. In this study we have utilized the tritiated, impermeant photolabel 2-N-[4-(1 -azi-2,2,2-trifluoroethyl)[2-3H]propyl]-1,3-bis(D-mannose-4-ylo xy)-2-propylamine to develop a technique to specifically measure the concentration of GLUT1 glucose transporters on the luminal surface of the endothelial cells of the BBB. We have combined this methodology with measurements of BBB glucose transport and immunoblot analysis of isolated brain microvessels for labeled luminal GLUT1 and total GLUT1 to reevaluate the effects of chronic hypoglycemia and diabetic hyperglycemia on transendothelial glucose transport in the rat. Hypoglycemia was induced with continuous-release insulin pellets (6 U/day) for a 12- to 14-day duration; diabetes was induced by streptozotocin (65 mg/kg i.p.) for a 14- to 21-day duration. Hypoglycemia resulted in 25-45% increases in regional BBB permeability-surface area (PA) values for D-[14C]glucose uptake, when measured at identical glucose concentration using the in situ brain perfusion technique. Similarly, there was a 23+/-4% increase in total GLUT1/mg of microvessel protein and a 52+/-13% increase in luminal GLUT1 in hypoglycemic animals, suggesting that both increased GLUT1 synthesis and a redistribution to favor luminal transporters account for the enhanced uptake. A corresponding (twofold) increase in cortical GLUT1 mRNA was observed by in situ hybridization. In contrast, no significant changes were observed in regional brain glucose uptake PA, total microvessel 55-kDa GLUT1, or luminal GLUT1 concentrations in hyperglycemic rats. There was, however, a 30-40% increase in total cortical GLUT1 mRNA expression, with a 96% increase in the microvessels. Neither condition altered the levels of GLUT3 mRNA or protein expression. These results show that hypoglycemia, but not hyperglycemia, alters glucose transport activity at the BBB and that these changes in transport activity result from both an overall increase in total BBB GLUT1 and an increased transporter concentration at the luminal surface.
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PMID:Blood-brain barrier glucose transporter: effects of hypo- and hyperglycemia revisited. 988 75

So far little is known about the importance of different types of non-diabetic hyperglycemia for the development of macrovascular disease. The aim of this work was to examine the intima-media thickness (IMT) of the common carotid artery (CCA), a well-accepted marker of atherosclerosis, as well as various risk factors for atherosclerosis in non-diabetic subjects with isolated fasting (IFH; n=67), isolated postchallenge (IPH; n=82) and combined hyperglycemia (CH; n=88) in comparison to normoglycemic (NG; n=265) controls. Subjects were participants of the RIAD study (Risk Factors in IGT for Atherosclerosis and Diabetes). IMT in the IPH (IMTmean: 0.89+/-0.02 mm; IMTmax: 1.01+/-0.02 mm; mean+/-SEM) and CH group (IMTmean: 0.91+/-0.02 mm; IMTmax: 1.03+/-0.02 mm) was significantly increased vs. the NG (IMTmean: 0.82+/-0.01 mm; IMTmax: 0.94+/-0.01 mm) and IFH group (IMTmean: 0.81+/-0.02 mm; IMTmax: 0.90+/-0.03 mm). IMT of the IFH group was similar to the normoglycemic controls. Subjects in the first and second tertile for postchallenge plasma glucose have similar carotid IMT irrespective of the level of fasting plasma glucose. The individuals of the third tertile for 2 h plasma glucose, whether in the first, second or third tertile of fasting plasma glucose, showed the same carotid IMT, which was significantly higher than all other groups, except for the one with lowest tertile for fasting and postchallenge plasma glucose. Except for total cholesterol and von Willebrand factor the levels of all other risk parameters were significantly higher in the hyperglycemic groups in comparison to the normoglycemic controls. Among the hyperglycemic subjects the CH group was at the highest risk for atherosclerosis with significantly increased levels of plasma triglycerides, fibrinogen, PAI-1, albuminuria, HDL-triglycerides, free fatty acids, insulin and proinsulin, and significantly reduced HDL-cholesterol in comparison to the normoglycemic controls. In summary, postchallenge hyperglycemia within the non-diabetic range is associated with atherosclerosis, as measured by the increased intima-media thickness of the common carotid artery. Furthermore, cardiovascular risk factors are significantly raised in all types of non-diabetic hyperglycemia.
Exp Clin Endocrinol Diabetes 2000
PMID:Prevalence and atherosclerosis risk in different types of non-diabetic hyperglycemia. Is mild hyperglycemia an underestimated evil? 1082 15

The brain requires oxygen and glucose for energy metabolism. Electroencephalogram (EEG) was recorded to determine the effect of glucose concentration on the cerebral function in hypoxic episode. Rats were divided into 3 groups: a streptozotocin-induced diabetic hyperglycaemic group, a normoglycaemic group, and an insulin-induced hypoglycaemic group. Hypoxia was induced by ventilating with 100% N2 for 3 min. EEG amplitude both 5 and 10 min after anoxia loading was higher in the diabetic hyperglycaemic than in the normoglycaemic group, though not significantly. Time for decreasing the EEG amplitude during anoxia loading was significantly longer in the hyperglycaemic than in the normoglycaemic group. Time for recovering the EEG amplitude after anoxia loading was significantly shorter in the hyperglycaemic group and was longer, though not significantly, in the hypoglycaemic group than in the normoglycaemic one. These results suggest the brain is more tolerant to hypoxia during diabetic hyperglycaemia than during normoglycaemia.
Diabetes Nutr Metab 2000 Apr
PMID:Streptozotocin-induced diabetic hyperglycaemia produces more EEG activity than normoglycaemia and hypoglycaemia during and after anoxia loading in rats. 1089 22

The current criteria for the diagnosis of diabetes used in France are now based on those published by the American Diabetes Association in 1997: fasting plasma glucose >/= 7.0 mmol/l (126 mg/dl) (previously >/= 7.8 mmol/l (140 mg/dl)), 2-hour glucose >/= 11.1 mmol/l (200 mg/dl) following a 75g oral glucose tolerance test. However, while the American Diabetes Association recommended that the post charge test not be used, both the World Health Organisation and the French Language Association for the study of Diabetes and Metabolic diseases (ALFEDIAM) retained this test. The DECODE (Diabetes Epidemiology: Collaborative analysis of Diagnostic criteria in Europe) study analysed the effect of these changes on the prevalence of diabetes, and whether the changes were justified by the mortality in the various glycaemic groups, using epidemiological data on close to 30,000 subjects from twenty European epidemiological studies. The prevalence of diabetes, using fasting rather than the 2-hour glucose concentrations (as had previously been recommended for epidemiological studies) resulted in changes in the prevalence of diabetes, an increase or a decrease, depending on the population studied. The fasting criteria tended to diagnose younger and more obese subjects than the 2-hour criteria. The subjects who would now be diabetic with the new fasting diagnostic criteria suffered a high mortality, similar to that of other diabetic subjects, thus the new criteria can be justified. However, the diabetic subjects who only have a post-charge diabetic hyperglycaemia (>/= 11.1 mmol/l (200 mg/dl)), are now even less likely to be screened as diabetic, despite the fact that they have a risk of premature death of the same order as other diabetic subjects.
Diabetes Metab 2000 Sep
PMID:The DECODE study. Diabetes epidemiology: collaborative analysis of diagnostic criteria in Europe. 1101 Dec 20

Vacuolization of the renal tubular epithelial cells (the Armanni-Ebstein lesion) associated with diabetic hyperglycemia is usually regarded as an accumulation of glycogen. In a case of death of diabetic coma, the vacuoles were stained strongly for lipids. This observation may have both clinical and therapeutic consequences, and may increase our knowledge of the metabolism in diabetes.
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PMID:Lipids in the proximal tubules of the kidney in diabetic coma. 1111 9

Peptidic glucagon antagonists have been shown to lower blood glucose levels in diabetic models (1-3), but attempts to identify small molecular weight glucagon receptor-binding antagonists have met with little success. Skyrin, a fungal bisanthroquinone, exhibits functional glucagon antagonism by uncoupling the glucagon receptor from adenylate cyclase activation in rat liver membranes (1). We have examined the effects of skyrin on cells transfected with the human glucagon receptor and on isolated rat and human hepatocytes. The skyrin used was isolated from Talaromyces wortmanni American Type Culture Collection 10517. In rat hepatocytes, skyrin (30 micromol/l) inhibited glucagon-stimulated cAMP production (53%) and glucose output (IC50 56 micromol/l). There was no detectable effect on epinephrine or glucagon-like peptide 1 (GLP-1) stimulation of these parameters, which demonstrates skyrin's selective activity. Skyrin was also evaluated in primary cultures of human hepatocytes. Unlike cell lines, which are largely unresponsive to glucagon, primary human hepatocytes exhibited glucagon-dependent cAMP production for 14 days in culture (EC50 10 nmol/l). Skyrin (10 micromol/l) markedly reduced glucagon-stimulated cAMP production (55%) and glycogenolysis (27%) in human hepatocytes. The inhibition of glucagon stimulation was a specific property displayed by skyrin and oxyskyrin but not shared by other bisanthroquinones. Skyrin is the first small molecular weight nonpeptidic agent demonstrated to interfere with the coupling of glucagon to adenylate cyclase independent of binding to the glucagon receptor. The data presented in this study indicate that functional uncoupling of the human glucagon receptor from cAMP production results in metabolic effects that could reduce hepatocyte glucose production and hence alleviate diabetic hyperglycemia.
Diabetes 2000 Dec
PMID:Effects of skyrin, a receptor-selective glucagon antagonist, in rat and human hepatocytes. 1111 10

We examined whether delayed gastric emptying could be produced by diabetes in dogs. Diabetes was produced by a single injection of streptozotocin (30 mg/kg i.v.), and diabetic hyperglycemia was observed from 2 to 15 months after injection. The plasma acetaminophen concentration, which is an indirect indicator of the gastric emptying rate, was delayed in 2 of 5 diabetic dogs from 15 months after the induction of diabetes. The effects of SK-951, a benzofuran derivative, on delayed gastric emptying were also examined in diabetic gastroparetic dogs in comparison with those of cisapride. SK-951 (1 mg/kg i.v.) significantly enhanced delayed gastric emptying in diabetic dogs, but cisapride (1 mg/kg i.v.) had no effect. In addition, SK-951 increased the plasma glucose levels in a manner correlated with its effect on gastric emptying. The present study suggested that SK-951 may be useful in the treatment of diabetic gastroparesis.
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PMID:Gastric emptying in diabetic gastroparetic dogs: ffects of SK-951,a novel prokinetic agent. 1115 Sep 19

Little is known about how hyperglycemia in diabetes directly affects renal and cardiovascular function. Therefore, we modified the streptozotocin-model of Type I diabetes in rats to enable chronic cardiovascular study at the earliest stages of diabetes, before there was time for development of vascular structural changes. We showed that the onset of diabetic hyperglycemia increased total peripheral resistance, decreased skeletal muscle blood flow, increased thromboxane production, and caused a transient increase in plasma renin activity (PRA). Mean arterial pressure (MAP) also increased, but the amplitude was modest. Moreover, we measured significant increases in glomerular filtration rate (GFR) and renal plasma flow, and also showed that endothelially mediated vasodilation in skeletal muscle was not impaired. We then tested the hypothesis that nitric oxide (NO) was playing an important role in counteracting a pressor response to the onset of diabetes. Our results showed that induction of diabetes in rats with chronic NO synthase inhibition caused a marked and progressive increase in MAP. In addition, PRA increased progressively under those conditions and the increase in GFR was prevented. This suggests that NO may work to keep arterial pressure in control at the onset of hyperglycemia very early in the development of diabetes, possibly by facilitating renal vasodilation and by suppressing activity of the renin-angiotensin system. However, the mechanisms for these interactions and the role of renal vascular resistance and other factors in mediating the hypertensive response remain unknown.
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PMID:Arterial pressure control at the onset of type I diabetes: the role of nitric oxide and the renin-angiotensin system. 1141 47

Abnormal availability of neurotrophins, such as nerve growth factor (NGF), has been implicated in diabetic somatosensory polyneuropathy. However, the involvement of neurotrophins in diabetic neuropathy of autonomic nerves, particularly the vagus nerve which plays a critical role in visceral afferent and in autonomic motor functions, is unknown. To assess the effects of hyperglycemia on the neurotrophin content and transport in this system, cervical vagus nerves of streptozotocin (STZ)-induced diabetic rats were studied at 8, 16, and 24 weeks after the induction of diabetes. Elevations in vagus nerve hexose (glucose and fructose) and polyol levels (sorbitol), and their normalization with insulin treatment, verified that the STZ treatment resulted in hyperglycemia-induced metabolic abnormalities in the nerve. Neurotrophin (NGF and neurotrophin-3; NT-3) content and axonal transport were assessed in the cervical vagus nerves from nondiabetic control rats, STZ-induced diabetic rats, and diabetic rats treated with insulin. The NGF, but not the NT-3, content of intact vagus nerves from diabetic rats was increased at 8 and 16 weeks (but not at 24 weeks). Using a double-ligation model to assess the transport of endogenous neurotrophins, the retrograde transport of both NGF and NT-3 was found to be significantly reduced in the cervical vagus nerve at later stages of diabetes (16 and 24 weeks). Anterograde transport of NGF or NT-3 was not apparent in the vagus nerve of diabetic or control rats. These data suggest that an increase in vagus nerve NGF is an early, but transient, response to the diabetic hyperglycemia and that a subsequent reduction in neuronal access to NGF and NT-3 secondary to decreased retrograde axonal transport may play a role in diabetes-induced damage to the vagus nerve.
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PMID:Streptozotocin-induced diabetes causes metabolic changes and alterations in neurotrophin content and retrograde transport in the cervical vagus nerve. 1142 92


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