scholarly journals Isolation of insulin-sensitive phosphatidylinositol-glycan from rat adipocytes. Its impaired breakdown in the streptozotocin-diabetic rat

1990 ◽  
Vol 271 (2) ◽  
pp. 427-435 ◽  
Author(s):  
S L Macaulay ◽  
R G Larkins
Keyword(s):  
Phospholipase C ◽  
Pyruvate Dehydrogenase ◽  
Cell Types ◽  
Solvent System ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Rat Adipocytes ◽  
Impaired Insulin ◽  
Streptozotocin Diabetic Rats ◽  
Concentration Response Curve

In this study an insulin-sensitive glycophospholipid from rat adipocytes was isolated and partially characterized. A material that activated pyruvate dehydrogenase was extracted from rat adipocyte membrane supernatants. Its release was stimulated by insulin and phosphatidylinositol-specific-phospholipase C and its activity was destroyed by nitrous acid deamination. These findings suggested that insulin might stimulate breakdown of a glycophospholipid containing inositol and glucosamine, as previously reported for some other cell types [Low & Saltiel (1988) Science 239, 268-275]. A lipid that incorporated [3H]glucosamine, [3H]galactose, [3H]inositol, and [3H]myristate and whose turnover was stimulated by insulin was subsequently isolated from intact adipocytes by sequential t.l.c. using an acidic solvent system followed by a basic solvent system. The effects of insulin on turnover of the lipid in these cells were transient, with maximal effects at 1 min, and there was a typical concentration-response curve to insulin (0.07 nM-7 nM), with effects being detected over the physiological range of insulin concentrations. In contrast with studies in other cells, there was appreciable turnover of the sugar labels. The majority of the [3H]glucosamine and [3H]galactose labels were cycled through to triacylglycerol in the adipocyte. However, of that recovered in the glycophospholipid band, a major proportion (less than 40%) was recovered as the native label. Digestion of the purified molecule with phosphatidylinositol-specific phospholipase C generated a material that activated both pyruvate dehydrogenase and low-Km cyclic AMP phosphodiesterase. Impairment in insulin-stimulated breakdown of the molecule in adipocytes of streptozotocin-diabetic rats was found, consistent with the impaired insulin activation of pyruvate dehydrogenase and glucose utilization seen in this model. These findings suggest that insulin stimulates breakdown of this glycophospholipid by stimulating an insulin-sensitive phospholipase in adipocytes. This compound may serve a function as a precursor for intracellular insulin mediators.

scholarly journals Oxidative Stress in Rats After 60 Days of Hypergalactosemia or Hyperglycemia

2003 ◽  
Vol 22 (6) ◽  
pp. 423-427 ◽  
Author(s):  
Mary Otsyula ◽  
Matthew S. King ◽  
Tonya G. Ketcham ◽  
Ruth A. Sanders ◽  
John B. Watkins
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Superoxide Dismutase ◽  
Glutathione Peroxidase ◽  
Insulin Treatment ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Glutathione Disulfide ◽  
Hepatic Lipid Peroxidation ◽  
Streptozotocin Diabetic Rats

Two of the models used in current diabetes research include the hypergalactosemic rat and the hyperglucosemic, streptozotocin-induced diabetic rat. Few studies, however, have examined the concurrence of these two models regarding the effects of elevated hexoses on biomarkers of oxidative stress. This study compared the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase and the concentrations of glutathione, glutathione disulfide, and thiobarbituric acid reactants (as a measure of lipid peroxidation) in liver, kidney, and heart of Sprague-Dawley rats after 60 days of either a 50% galactose diet or insulin deficiency caused by streptozotocin injection. Most rats from both models developed bilateral cataracts. Blood glucose and glycosy-lated hemoglobin A1c concentrations were elevated in streptozotocin diabetic rats. Streptozotocin diabetic rats exhibited elevated activities of renal superoxide dismutase, cardiac catalase, and renal and cardiac glutathione peroxidase, as well as elevated hepatic lipid peroxidation. Insulin treatment of streptozotocin-induced diabetic rats normalized altered markers. In galactosemic rats, hepatic lipid peroxidation was increased whereas glutathione reductase activity was diminished. Glutathione levels in liver were decreased in diabetic rats but elevated in the galactosemic rats, whereas hepatic glutathione disulfide concentrations were decreased much more in diabetes than in galactosemia. Insulin treatment reversed/prevented all changes caused by streptozotocin-induced diabetes. Lack of concomitance in these data indicate that the 60-day galactose-fed rat is not experiencing the same oxidative stress as the streptozotocin diabetic rat, and that investigators must be cautious drawing conclusions regarding the concurrence of the effects of the two animal models on oxidative stress biomarkers.

scholarly journals 3-oxo acid coenzyme A-transferase in normal and diabetic rat muscle

1976 ◽  
Vol 158 (2) ◽  
pp. 509-512 ◽  
Author(s):  
A Fenselau ◽  
K Wallis
Keyword(s):  
Skeletal Muscle ◽  
Coenzyme A ◽  
Substrate Inhibition ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Functional Parameters ◽  
Rat Muscle ◽  
Coa Transferase ◽  
Normal Rat ◽  
Streptozotocin Diabetic Rats

The amounts of succinyl-CoA--3-oxo acid CoA-transferase (EC 2.8.3.5) decrease progressively in skeletal muscle in streptozotocin-diabetic rats, reaching after 10 days about 50% of the value in normal rat muscle. Electrofocusing studies indicate the occurrence of partial proteolysis of the enzyme in diabetic muscle. However, several functional parameters relating to acetoacetate utilization, including substrate inhibition, are quite similar for muscle transferase preparations from normal and diseased rats. The development of pathological ketoacidosis is discussed in the light of these observations.

Increased expression of cyclooxygenase-1 and -2 in the diabetic rat renal medulla

2003 ◽  
Vol 285 (6) ◽  
pp. F1068-F1077 ◽  
Author(s):  
Rania Nasrallah ◽  
Anne Landry ◽  
Sonia Singh ◽  
Monika Sklepowicz ◽  
Richard L. Hébert
Keyword(s):  
Collecting Duct ◽  
Renal Medulla ◽  
Immunohistochemical Analysis ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Fourfold Increase ◽  
Protein Levels ◽  
Cyclooxygenase 1 ◽  
Streptozotocin Diabetic Rats ◽  
Medullary Collecting Duct

Alterations in renal prostaglandins (PGs) may contribute to some of the renal manifestations in diabetes leading to nephropathy. PG production is dependent on the activity of cyclooxygenases (COX-1 AND -2) and PG synthases. Our present study investigated levels of these enzymes in streptozotocin-diabetic rats at 2, 4, 6, and 8 wk of diabetes. Immunohistochemical analysis revealed an increase in COX signal in the inner and outer medulla of diabetic rats. This was confirmed by Western blotting, showing up to a fourfold increase in both COX isoforms at 4–6 wk of diabetes. Also, Western blot analysis revealed a sixfold increase in PGE2 synthase expression in the outer medullary region of 6-wk diabetic rats but no difference in the inner medulla. In cultured rat inner medullary collecting duct (IMCD), levels of COX were increased two- to threefold in cells exposed for 4 days to 37.5 mM glucose compared with control of 17.5 mM. While no change in PGE2 synthase levels was noted, PGE2 synthesis was increased. Furthermore, levels of EP1 and EP4 mRNA were increased, as well as a twofold increase in EP4 protein levels. Future studies will determine which COX isoform is contributing to the majority of PGE2 produced in the diabetic IMCD and the significance of these findings to disturbances in IMCD function and to the progression of diabetic nephropathy.

scholarly journals Differential impact of adipokines derived from primary adipocytes of wild-type versus streptozotocin-induced diabetic rats on glucose and fatty acid metabolism in cardiomyocytes

2008 ◽  
Vol 199 (3) ◽  
pp. 389-397 ◽  
Author(s):  
Rengasamy Palanivel ◽  
Vivian Vu ◽  
Min Park ◽  
Xiangping Fang ◽  
Gary Sweeney
Keyword(s):  
Heart Failure ◽  
Fatty Acid ◽  
Glucose Uptake ◽  
Conditioned Medium ◽  
Fatty Acid Uptake ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Acid Uptake ◽  
Wild Type ◽  
Rat Adipocytes

The causal relationship between obesity and cardiovascular disease is extensively acknowledged; however, the exact mechanisms linking obesity and heart failure remain unclear. Here, we investigated the influence of adipokines derived from primary adipocytes on glucose and fatty acid uptake and metabolism in isolated primary cardiomyocytes. Either co-culture of these cell types or incubation with adipocyte-conditioned medium significantly increased glucose uptake in cardiomyocytes. When streptozotocin-induced diabetic rats were used as a source of adipocytes, there was a lower ability to elicit glucose uptake in cardiomyocytes which corresponded with lower Akt and AMPK phosphorylation. The profile of glucose metabolism also differed with oxidation being favored upon co-culture with wild-type adipocytes whereas lactate production was strongly induced by adipocytes from diabetic rats. Examination of fatty acid uptake revealed that stimulation only occurred in response to adipokines secreted by wild-type rat adipocytes. Importantly, oxidation of fatty acids by cardiomyocytes was decreased by adipokines derived from diabetic rat adipocytes. Analysis of adipokine profiles in diabetic rat adipocyte-conditioned medium demonstrated the most significant decreases in adiponectin and leptin with increased IL6 expression. Taken together, these data suggest that the profile of adipokines secreted by adipocytes from diabetic rats have a deleterious influence on cardiomyocyte metabolism which may be of relevance in the pathophysiology of heart failure.

Lack of effect of thyroid hormone on diabetic rat heart function and biochemistry

1984 ◽  
Vol 62 (6) ◽  
pp. 617-621 ◽  
Author(s):  
Arun G. Tahiliani ◽  
John H. McNeill
Keyword(s):  
Heart Function ◽  
Myocardial Dysfunction ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Diabetic Rat ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Chain Acyl ◽  
Uptake Activity ◽  
Streptozotocin Diabetic Rats ◽  
Developed Pressure

Cardiac functional abnormalities are frequently seen in diabetics and diabetes is also known to produce a state of mild hypothyroidism. To study the degree of involvement of diabetes-induced hypothyroidism on altered myocardial function, thyroid replacement therapy was carried out in streptozotocin-diabetic rats. Triiodothyronine (T3) treatment was initiated 3 days after the rats were made diabetic and was carried out for 6 weeks thereafter. Isolated perfused hearts from diabetic rats exhibited a depression in left ventricular developed pressure and positive and negative dP/dt at higher filling pressures as compared with controls. The depression could not be prevented by thyroid treatment. Calcium uptake activity in the cardiac sarcoplasmic reticulum (SR) was also depressed as a result of diabetes and this depression also was not prevented by thyroid treatment. Long chain acyl carnitine levels were found to be elevated in diabetic cardiac SR and could not be lowered by T3 treatment. The results indicate that the myocardial dysfunction observed in diabetic rats is due to factors other than the induced hypothyroidism.

scholarly journals Catecholamine activation of pyruvate dehydrogenase in white adipose tissue of the rat in vivo

1987 ◽  
Vol 241 (2) ◽  
pp. 415-419 ◽  
Author(s):  
E Kilgour ◽  
R G Vernon
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Pyruvate Dehydrogenase ◽  
Serum Insulin ◽  
Diabetic Rats ◽  
Maximum Effect ◽  
White Adipocytes ◽  
Streptozotocin Diabetic Rats

Intraperitoneal injections of noradrenaline or adrenaline into rats increased the proportion of pyruvate dehydrogenase in the active state in white adipose tissue; this effect of catecholamines was also apparent in streptozotocin-diabetic rats, showing that it was not due to an increase in serum insulin concentration. The catecholamine-induced increase in pyruvate dehydrogenase of white adipose tissue in vivo was completely blocked by prior injection of either the beta-antagonist propranolol or the alpha 1-antagonist prazosin. Cervical dislocation of conscious rats increased pyruvate dehydrogenase activity of white adipose tissue, which was prevented by prior injection of propranolol. Adrenaline (30 nM) activated pyruvate dehydrogenase in white adipocytes in vitro; the maximum effect of adrenaline required activation of both alpha 1- and beta-receptors. The results show that catecholamines activate pyruvate dehydrogenase of white adipose tissue both in vivo and in vitro and that this effect is mediated by a combination of alpha 1- and beta-adrenergic receptors.

Reduced transcoronary exchange and prostaglandin synthesis in diabetic rat heart

1984 ◽  
Vol 247 (4) ◽  
pp. H563-H569
Author(s):  
P. Rosen ◽  
R. Rosen ◽  
C. Hohl ◽  
H. Reinauer ◽  
W. Klaus
Keyword(s):  
Arachidonic Acid ◽  
Diabetic Rats ◽  
Prostaglandin Synthesis ◽  
Diabetic Rat ◽  
First Order ◽  
Basal Release ◽  
Streptozotocin Diabetic Rats ◽  
Pseudo First Order ◽  
Perfused Hearts ◽  
Kinetics Of

In perfused hearts of streptozotocin-diabetic rats the kinetics of a fluoresce indicator transit was measured after pulse injection of FITC-dextran 3. The fluorescence changes on the left ventricle could be described by two pseudo first-order processes with half times in the range of seconds (t/2) corresponding to the intravascular washout and a slow process (T/2) corresponding to the exchange between the extra- and the intravascular space. In diabetes both half times became prolonged, and the amount of FITC-dextran 3 exchanged between the two compartments was reduced, indicating an impaired transcoronary transport in diabetic hearts. There was a time-dependent reduction in the basal release of prostacyclin in hearts of control and diabetic rats. However, studied hearts of diabetic rats released less 6-keto-prostaglandin F1 alpha (PGF1 alpha) than controls. This impaired release of 6-oxo-PGF1 alpha could be prevented partly by adrenalectomy. Because diabetic hearts release more 6-oxo-PGF1 alpha than controls after application of arachidonic acid, these data suggest that the supply of arachidonic acid for the synthesis of prostaglandins is impaired in diabetes, but not the cyclooxygenase pathway itself. The reduced transcoronary transport and the impaired synthesis of prostacyclin might be early steps in the development of microangiopathic myocardial alterations in diabetes.

scholarly journals Renal protective effect of chronic inhibition of COX-2 with SC-58236 in streptozotocin-diabetic rats

2011 ◽  
Vol 300 (6) ◽  
pp. H2316-H2322 ◽  
Author(s):  
J. Quilley ◽  
M. Santos ◽  
P. Pedraza
Keyword(s):  
Urinary Excretion ◽  
Structural Changes ◽  
Weight Ratio ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Protective Effects ◽  
Renal Protection ◽  
Tnf Α ◽  
Streptozotocin Diabetic Rats ◽  
Cox 2

The induction of renal cyclooxygenase-2 (COX-2) in diabetes has been implicated in the renal functional and structural changes in models where hypertension or uninephrectomy was superimposed. We examined the protective effects of 3 mo treatment of streptozotocin-diabetic rats with a highly selective COX-2 inhibitor (SC-58236) in terms of albuminuria, renal hypertrophy, and the excretion of TNF-α and TGF-β, which have also been implicated in the detrimental renal effects of diabetes. SC-58236 treatment (3 mg·kg−1·day−1) of diabetic rats resulted in reduced urinary excretion of PGE2, 6-ketoPGF1α, and thromboxane B2, all of which were increased in the diabetic rat compared with age-matched nondiabetic rats. However, serum thromboxane B2 levels were unchanged, confirming the selectivity of SC-58236 for COX-2. The renal protective effects of treatment of diabetic rats with the COX-2 inhibitor were reflected by a marked reduction in albuminuria, a reduction in kidney weight-to-body weight ratio, and TGF-β excretion and a marked decrease in the urinary excretion of TNF-α. The protective effects of SC-58236 were independent of changes in plasma glucose levels or serum advanced glycation end-product levels, which were not different from those of untreated diabetic rats. In an additional study, the inhibition of COX-2 with SC-58236 for 4 wk in diabetic rats resulted in creatinine clearance rates not different from those of control rats. These results confirm that the inhibition of COX-2 in the streptozotocin-diabetic rat confers renal protection and suggest that the induction of COX-2 precedes the increases in cytokines, TNF-α, and TGF-β.

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