scholarly journals Glutamine and ketone-body metabolism in the gut of streptozotocin-diabetic rats

1988 ◽  
Vol 249 (2) ◽  
pp. 565-572 ◽  
Author(s):  
M S M Ardawi

1. In short- and long-term diabetic rats there is a marked increase in size of both the small intestine and colon, which was accompanied by marked decreases (P less than 0.001) and increases (P less than 0.001) in the arterial concentrations of glutamine and ketone bodies respectively. 2. Portal-drained viscera blood flow increased by approx. 14-37% when expressed as ml/100 g body wt., but was approximately unchanged when expressed as ml/g of small intestine of diabetic rats. 3. Arteriovenous-difference measurements for ketone bodies across the gut were markedly increased in diabetic rats, and the gut extracted ketone bodies at approx. 7 and 60 nmol/min per g of small intestine in control and 42-day-diabetic rats respectively. 4. Glutamine was extracted by the gut of control rats at a rate of 49 nmol/min per g of small intestine, which was diminished by 45, 76 and 86% in 7-, 21- and 42-day-diabetic rats respectively. 5. Colonocytes isolated from 7- or 42-day-diabetic rats showed increased and decreased rates of ketone-body and glutamine metabolism respectively, whereas enterocytes of the same animals showed no apparent differences in the rates of acetoacetate utilization as compared with control animals. 6. Prolonged diabetes had no effects on the maximal activities of either glutaminase or ketone-body-utilizing enzymes of colonic tissue preparations. 7. It is concluded that, although the epithelial cells of the small intestine and the colon during streptozotocin-induced diabetes exhibit decreased rates of metabolism of glutamine, such decreases were partially compensated for by enhanced ketone-body utilization by the gut mucosa of diabetic rats.

1987 ◽  
Vol 242 (1) ◽  
pp. 61-68 ◽  
Author(s):  
M Watford ◽  
E J Erbelding ◽  
E M Smith

The small intestine is the major site of glutamine utilization in the mammalian body. During prolonged (40-day) streptozotocin-diabetes in the rat there is a marked increase in both the size and the phosphate-activated glutaminase activity of the small intestine. Despite this increased capacity, intestinal glutamine utilization ceases in diabetic rats. Mean arterial glutamine concentration fell by more than 50% in diabetic rats, suggesting that substrate availability is responsible for the decrease in intestinal glutamine use. When arterial glutamine concentrations in diabetic rats were elevated by infusion of glutamine solutions, glutamine uptake across the portal-drained viscera was observed. The effect of other respiratory fuels on intestinal glutamine metabolism was examined. Infusions of ketone bodies did not affect glutamine use by the portal-drained viscera of non-diabetic rats. Prolonged diabetes had no effect on the activity of 3-oxoacid CoA-transferase in the small intestine or on the rate of ketone-body utilization in isolated enterocytes. Glutamine (2 mM) utilization was decreased in enterocytes isolated from diabetic rats as compared with those from control animals. However, glutaminase activity in homogenates of enterocytes was unchanged by diabetes. In enterocytes isolated from diabetic rats the addition of ketone bodies or octanoate decreased glutamine use. It is proposed that during prolonged diabetes ketone bodies, and possibly fatty acids, replace glutamine as the major respiratory fuel of the small intestine.


2019 ◽  
Author(s):  
Engelbert Buxbaum

The long-term (34 weeks) effect of streptozotocin induced diabetes was assessed in Wistar rats.Na+/K+-ATPase activity was measured by ouabain inhibitable 86Rb+-uptake into erythrocytes. No difference in the rate of Rb+-uptake, the Km for Rb+ or the Ki for ouabain was detected between normal and diabetic rats. Thus, the change in Na+/K+-ATPase activity repeatedly described in short-term studies may not translate into a long term physiologically relevant change in ion flux through the sodium pump.Rats excrete ketone bodies mainly as β-hydroxybutyrate. This compound does not show up with nitroprusside sodium based test sticks, it can however be detected by coupled spectrophotometric assay with hydroxybutyrate dehydrogenase.Almost half of the diabetic animals reverted to a non-diabetic state during the experiment, followed by at least partial reversal of secondary diabetic damage.Abbreviations usedPKCProtein kinase CDAGDiacylglycerolEDTAEthylenediamine tetraacetic acidPIP3Phosphatidylinositol trisphosphatePBSPhosphate buffered salinei.p.intraperitonealHBAβ-hydroxybutyric acidSTZstreptozotocinEnzymes: Na+/K+-exchanging ATP-phosphohydrolase (Na+/K+-ATPase), E.C. 7.2.2.13; (R)-3-hydroxybutanoate:NAD+ oxidoreductase [1.1.1.30] (β-hydroxybutyrate dehydro-genase)


2016 ◽  
Vol 11 (1) ◽  
pp. 200 ◽  
Author(s):  
Muhammad Kifayatullah ◽  
Pinaki Sengupta

<p class="Abstract">The purpose of this study was to evaluate the effects of <em>Pericampylus glaucus</em> extract on plasma glucose concentration and lipid profile in normal and streptozotocin-induced diabetic rats. The ethanolic extract were administered orally at three different doses (400, 600 and 800 mg/kg) and glibenclamide (20 mg/kg p.o.) for 21 days after 72 hours of streptozotocin injection. During the short- and long-term studies, the extract was found to possess significant (p&lt;0.01, p&lt;0.001) anti-diabetic activity in normal and diabetic rats compared with untreated normal and untreated diabetic group. It also caused reduction in the level of total cholesterol, triglyceride, and LDL etc. and improvement in the HDL level compared with untreated diabetic rats. Reduction in the fasting blood sugar, cholesterol, triglyceride, urea, LDL, creatinine levels and improvement in the HDL by<em> P. glaucus</em> indicates that plant has anti-diabetic activity along with anti hyperlipidemic efficacy and provides a scientific rationale for the use.</p><p> </p>


2012 ◽  
Vol 30 (6) ◽  
pp. 1528-1536 ◽  
Author(s):  
NABILA BENARIBA ◽  
RABEH DJAZIRI ◽  
BOUCHRA HANANE ZERRIOUH ◽  
WAFAA BELLAKHDAR ◽  
EMELINE HUPKENS ◽  
...  

2003 ◽  
Vol 44 (3) ◽  
pp. 347-353 ◽  
Author(s):  
F. Palm ◽  
P.-O. Carlsson ◽  
P. Hansell ◽  
O. Hellberg ◽  
A. Nygren ◽  
...  

Purpose: To investigate the effect of the contrast medium (CM) iopromide on renal microcirculation and oxygen tension in non-diabetic control and streptozotocin-diabetic Wistar Furth rats. Materials and Methods: Oxygen tension was measured with Clark-type microelectrodes and blood flow with laser-Doppler flow probes. In order to differentiate between an acutely increased blood glucose concentration and a long-term diabetic state, some of the non-diabetic control rats were intravenously infused with glucose. Results: CM decreased the medullary oxygen tension in control (non-diabetic normoglycemic) rats (∼35%) but not in diabetic rats. Medullary blood flow in control rats increased after CM administration and remained elevated, while it was unchanged in the diabetic rats. In response to CM, glucose-infused control rats responded similarly to control animals in medullary oxygen tension, but similarly to diabetic rats in medullary blood flow. Contrary to in control rats, medullary oxygen tension was unchanged in diabetic animals after CM administration. Conclusion: Streptozotocin-diabetic rats have an altered response to intravenous injection of the CM iopromide compared to non-diabetic rats. The unaltered medullary oxygen tension, seen in the diabetic group after injection of CM, suggests that non-hemodynamic mechanisms are responsible for the increased frequency of renal failure commonly seen among diabetic patients.


1992 ◽  
Vol 127 (1) ◽  
pp. 81-85 ◽  
Author(s):  
Hitoshi Ishida ◽  
Yutaka Seino ◽  
Noritaka Takeshita ◽  
Takeshi Kurose ◽  
Kazuo Tsuji ◽  
...  

Diabetic osteopenia has been known as one of the chronic complications of diabetes mellitus, and a decrease in bone turnover has been thought to be one of the pathophysiological characteristics of this complication. In order to investigate the effect of long-term insulin therapy on low bone turnover in diabetes, pancreas transplantation was performed on streptozotocin-induced diabetic rats. Plasma levels of bone γ-carboxyglutamic acid-containing protein(osteocalcin) in untreated diabetic rats were 0.9±0.1 (mean±sem) nmol/l, significantly lower than the value of 4.2±0.6 nmol/l in control rats (p<0.01). Pancreas transplantation reversed this decrease to 6.3±1.1 nmol/l, which was not significantly different from the value in control rats. The circulating levels of calcitriol were significantly decreased in the untreated diabetic group (p<0.01), and the decrease was fully reversed by pancreas transplantation. In addition, the decreases in bone length, strength and weight were also improved by the transplantation. This evidence clearly shows that the improvement of metabolic derangements in diabetes by insulin is essential for the prevention of deterioration in diabetic osteopenia. It is possible, therefore, that insulin exerts an indirect beneficial influence through the metabolic amelioration on the decreases in bone turnover and circulating osteocalcin in diabetes mellitus, or has a direct stimulatory effect on the osteoblasts via the insulin receptor since its presence has been shown recently in osteoblastic cells.


1985 ◽  
Vol 230 (2) ◽  
pp. 329-337 ◽  
Author(s):  
H Osmundsen ◽  
K Bjørnstad

Evidence showing that some unsaturated fatty acids, and in particular docosahexaenoic acid, can be powerful inhibitors of mitochondrial β-oxidation is presented. This inhibitory property is, however, also observed with the cis- and trans-isomers of the C18:1(16) acid. Hence it is probably the position of the double bond(s), and not the degree of unsaturation, which confers the inhibitory property. It is suggested that the inhibitory effect is caused by accumulation of 2,4-di- or 2,4,7-tri-enoyl-CoA esters in the mitochondrial matrix. This has previously been shown to occur with these fatty acids, in particular when the supply of NADPH was limiting 2,4-dienoyl-CoA reductase (EC 1.3.1.-) activity [Hiltunen, Osmundsen & Bremer (1983) Biochim. Biophys. Acta 752, 223-232]. Liver mitochondria from streptozotocin-diabetic rats showed an increased ability to β-oxidize 2,4-dienoyl-CoA-requiring acylcarnitines. Docosahexaenoylcarnitine was also found to be less inhibitory at lower concentrations with incubation under coupled conditions. With uncoupling conditions there was little difference between mitochondria from normal and diabetic rats in these respects. This correlates with a 5-fold stimulation of 2,4-dienoyl-CoA reductase activity found in mitochondria from streptozotocin-diabetic rats.


Diabetologia ◽  
1993 ◽  
Vol 36 (3) ◽  
pp. 218-224 ◽  
Author(s):  
M. C. Cam ◽  
R. A. Pederson ◽  
R. W. Brownsey ◽  
J. H. McNeill

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