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STZ-treated Rats (STZ-treat + rat)
Selected AbstractsDiabetes and mitochondrial bioenergetics: Alterations with ageJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 4 2003Fernanda M. Ferreira Abstract Several studies have been carried out to evaluate the alterations in mitochondrial functions of diabetic rats. However, some of the results reported are controversial, since experimental conditions, such as aging, and/or strain of animals used were different. The purpose of this study was to evaluate the metabolic changes in liver mitochondria, both in the presence of severe hyperglycaemia (STZ-treated rats) and mild hyperglycaemia (Goto-Kakizaki (GK) rats). Moreover, metabolic alterations were evaluated both at initial and at advanced states of the disease. We observed that both models of type 1 and type 2 diabetes presented alterations on respiratory chain activity. Because of continual severe hyperglycaemia, 9 weeks after the induction of diabetes, the respiratory function declined in STZ-treated rats, as observed by membrane potential and respiratory ratios (RCR, P/O, and FCCP-stimulated respiration) assessment. In contrast, GK rats of 6 months age presented increased respiratory ratios. To localize which respiratory complexes are affected by diabetes, enzymatic respiratory chain activities were evaluated. We observed that succinate dehydrogenase and cytochrome c oxidase activities were significantly augmented both in STZ-treated rats and GK rats of 6 months age. Moreover, H+ -ATPase activity was also significantly increased in STZ-treated rats with 3 weeks of diabetes and in GK rats of 6 months age as compared to controls. Therefore, these results clearly suggest that both animal models of diabetes present some metabolic adjustments in order to circumvent the deleterious effects promoted by the high glucose levels typical of the disease. © 2003 Wiley Periodicals, Inc. J Biochem Mol Toxicol 17:214,222, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10081 [source] Quantifying hepatic glycogen synthesis by direct and indirect pathways in rats under normal ad libitum feeding conditionsMAGNETIC RESONANCE IN MEDICINE, Issue 1 2009Ana F. Soares Abstract Hepatic glycogen synthesis from intact hexose (direct pathway) relative to that from gluconeogenic precursors (indirect pathway) was quantified in ad libitum-fed rats. Following 2H2O administration and overnight feeding, the livers were removed and glycogen 2H-enrichment was measured by 2H NMR. Six controls and six rats rendered hyperglycemic by streptozotocin (STZ; fasting blood glucose = 385 ± 31 mg/dl) were studied. The indirect pathway contribution, estimated as glycogen hydrogen 5 relative to hydrogen 2 enrichment, was 54% ± 4% for control rats,similar to values from healthy, meal-fed humans. In STZ-treated rats, the indirect pathway contribution was significantly higher (68% ± 4%, P < 0.05 vs. controls), similar to that of Type 1 diabetic (T1D) patients. In conclusion, sources of hepatic glycogen synthesis in rats during ad libitum nocturnal feeding were quantified by analysis of glycogen enrichment from 2H2O. STZ caused alterations resembling the pathophysiology of hepatic glycogen synthesis in T1D patients. Magn Reson Med 61:1,5, 2009. © 2008 Wiley-Liss, Inc. [source] Insulin Is Essential for the Recovery from Allodynia Induced by Complete Freund's AdjuvantPAIN MEDICINE, Issue 9 2010Gregory P. Casey PhD Abstract Objective., To determine the effect of streptozotocin (STZ)-induced diabetes on the development and recovery of thermal and mechanical hyperalgesia associated with inflammation induced by subcutaneous injection of complete Freund's adjuvant (CFA). Background., The response to nociceptive injury in diabetes differs from that seen in normal individuals in that diabetic patients have increased susceptibility to infections and recover slowly or incompletely from infections and tissue injury due to an abnormal inflammatory response. We have chosen to examine the effect of STZ-induced hypoinsulinemia on the hyperalgesia associated with the enhanced inflammatory state that is induced by the subcutaneous injection of CFA to delineate the potential role of insulin in the development of chronic pain. Methods., STZ- and vehicle-treated Sprague-Dawley rats were tested using thermal and mechanical stimulation after subcutaneous injection of CFA. The behavioral response was compared with that similarly determined in non-diabetic controls and insulin-depleted rats that received insulin replacement. Results., Recovery of the thermal hyperalgesic response to baseline levels occurred over a period of 9,14 days, but the allodynic response to mechanical stimulation persisted for the duration of the study in STZ-treated rats. Insulin replacement prevented the delay in recovery of mechanical allodynia, but had no obvious effect on nociception in uninflamed tissue. Conclusions., Normal insulin function is essential for recovery from mechanical allodynia associated with inflammation induced by CFA. Altered insulin metabolism may selectively influence fiber-type specific mechanisms related to mechanical allodynia associated with inflammation and wound healing. [source] Inhibition of the formation or action of angiotensin II reverses attenuated K+ currents in type 1 and type 2 diabetesTHE JOURNAL OF PHYSIOLOGY, Issue 1 2001Yakhin Shimoni 1Transient and sustained calcium-independent outward K+ currents (It and ISS) as well as action potentials were recorded in cardiac ventricular myocytes isolated from two models of diabetes mellitus. 2Rats injected (i.v.) with streptozotocin (STZ, 100 mg kg,1) 6,10 days before cell isolation developed insulin-dependent (type 1) diabetes. It and ISS were attenuated and the action potential prolonged. Incubation of myocytes (6-9 h) with the angiotensin II (ATII) receptor blockers saralasin or valsartan (1 ,m) significantly augmented these currents. Inclusion of valsartan (1 g l,1) in the drinking water for 5,10 days prior to and following STZ injection partially prevented current attenuation. 3Incubation of myocytes from STZ-treated rats (6-9 h) with 1 ,m quinapril, an angiotensin-converting enzyme (ACE) inhibitor, significantly augmented It and ISS and shortened the ventricular action potential. It augmentation was not due to changes in steady-state inactivation or in recovery from inactivation. No acute effects of quinapril were observed. 4The effects of quinapril and valsartan were abolished by 2 ,m cycloheximide. 5Myocytes were isolated from the db/db mouse, a leptin receptor mutant that develops symptoms of non-insulin-dependent (type 2) diabetes. K+ currents in these cells were also attenuated, and the action potentials prolonged. Incubation of these cells (> 6 h) with valsartan (1 ,m) significantly enhanced the transient and sustained outward currents. 6These results confirm recent suggestions that cardiac myocytes contain a renin-angiotensin system, which is activated in diabetes. It is proposed that chronic release of ATII leads to changes in ionic currents and action potentials, which can be reversed by blocking the formation or action of ATII. This may underlie the proven benefits of ATII receptor blockade or ACE inhibition in diabetes, by providing protection against cardiac arrhythmias. [source] 1,,25-Dihydroxyvitamin D3 inhibits rat liver ultrastructural changes and the development of ,-glutamyltranspeptidase-positive foci in diethylnitrosamine-initiated and streptozotocin-induced diabetes-promoted hepatocarcinogenesisCELL BIOCHEMISTRY AND FUNCTION, Issue 3 2002Barun Kanti Saha Abstract In the present study, the chemopreventive effect of the active metabolite of vitamin D, 1,,25-dihydroxyvitamin D3 (VD3), against chemically-induced and diabetes-promoted rat liver carcinogenesis was investigated. Hepatocarcinogenesis was initiated with a single intraperitoneal (i.p.) injection of diethylnitrosamine (DEN) (125 mg kg,1 body weight) at week 4 followed by promotion with streptozotocin (STZ) (65 mg kg,1 body weight with a single i.p. injection) at week 7. With this basic experimental regimen, the effect of VD3 (0.3 ,g (0.1 ml),1 propylene glycol per os twice a week) was investigated with effect from 4 weeks prior to the exposure of DEN. The results showed that VD3 supplementation throughout the experimental period reduced the incidence, total number and multiplicity and altered the size of visible persistent nodules (PNs) in DEN- or DEN,+,STZ-treated rats as compared with their respective controls. In these two groups, it also caused a significant decrease in the number (p,<,0.002 and 0.001 respectively) and focal area (p,<,0.05) of ,-glutamyltranspeptidase (GGT)-positive hepatic foci. Moreover, continuous supplementation of VD3 exhibits a protective effect in maintaining the normal cellular architecture of the hepatocytes in DEN- or DEN,+,STZ-treated rats. Our results thus strongly suggest that VD3 is very effective in the inhibition of DEN-initiated and STZ-induced diabetes-promoted rat liver carcinogenesis. Copyright © 2002 John Wiley & Sons, Ltd. [source] | |||||||||||||