scholarly journals Elevated glutamine metabolism in splenocytes from spontaneously diabetic BB rats

1991 ◽  
Vol 274 (1) ◽  
pp. 49-54 ◽  
Author(s):  
G Wu ◽  
C J Field ◽  
E B Marliss
Keyword(s):  
Diabetic Rats ◽  
Glutamine Metabolism ◽  
Co2 Production ◽  
Diabetic Rat ◽  
Bb Rat ◽  
Isolated Cells ◽  
Atp Production ◽  
Glutamate Production ◽  
Insulin Dependent ◽  
Diabetic Syndrome

To investigate the metabolic fates of glutamine in splenocytes from the BB rat with spontaneous immunologically mediated insulin-dependent diabetes, freshly isolated cells were incubated in Krebs-Ringer Hepes buffer with 1.0 mM-[U-14C]glutamine and 0, 4 mM- or 15 mM-glucose. (1) The major products of glutamine metabolism in splenocytes from normal and diabetic rats were ammonia, glutamate, aspartate and CO2. (2) The addition of glucose increased (P less than 0.01) glutamate production, but decreased (P less than 0.01) aspartate and CO2 production from glutamine, as compared with the values obtained in the absence of glucose. However, there were no differences in these metabolites of glutamine at 4 mM- and 15 mM-glucose. (3) At all glucose concentrations used, the productions of ammonia, glutamate, aspartate and CO2 from glutamine were all markedly increased (P less than 0.01) in splenocytes from diabetic rats. (4) Potential ATP production from glutamine in the splenocytes was similar to that from glucose, and was increased in cells from the diabetic rat. (5) ATP concentrations were increased (P less than 0.01) in diabetic-rat splenocytes in the presence of glutamine with or without glucose. (6) Our results demonstrate that glutamine is an important energy substrate for splenocytes and suggest that the increased glutamine metabolism may be associated with the activation of certain subsets of splenocytes in the immunologically mediated diabetic syndrome.

Enhanced metabolism of glucose and glutamine in mesenteric lymph node lymphocytes from spontaneously diabetic BB rats

1994 ◽  
Vol 72 (7) ◽  
pp. 827-832 ◽  
Author(s):  
Catherine J. Field ◽  
Guoyao Wu ◽  
Errol B. Marliss
Keyword(s):  
Lymph Node ◽  
Glucose Metabolism ◽  
Mesenteric Lymph Node ◽  
Glutamine Metabolism ◽  
Diabetic Rat ◽  
Bb Rat ◽  
Atp Production ◽  
Mesenteric Lymph ◽  
Lymph Node Cells ◽  
In Cells

Increased energy substrate metabolism accompanies the functional activation of extrathymic immunocytes in the autoimmune BB diabetic rat, but the specific cells responsible have not been identified. To determine the possible contribution of lymphocytes to the elevated metabolism of glucose and glutamine, mesenteric lymph node cells were selected because they contain few macrophages or natural killer (NK) cells. Results from diabetic (BBd, n = 7) and non-diabetes-prone (BBn, n = 7) rats were compared with those from streptozotocin-induced diabetic (STZ-BBn, n = 6) rats. In BBd cells, all measured metabolites of glutamine (CO2, glutamate, aspartate, and NH3) in the presence of 5 mM glucose were elevated (1.5- to 2.5-fold) compared with BBn. In contrast, the only product of glucose metabolism (in the presence of 2 mM glutamine) that was increased was pyruvate (1.6-fold). All measured products of glucose metabolism were significantly lower in cells from STZ-BBn than from BBn rats. Products from glutamine did not differ. Calculated potential ATP production was greater (p < 0.05) in BBd than in BBn and STZ-BBn cells (86 ± 5 vs. 65 ± 2 and 53 ± 5 nmol∙2 h−1∙10−6 cells, respectively). However, in BBn and STZ-BBn rats, about three quarters of the cells were T (CD5+) cells and one quarter were B (MARK-1+) cells, whereas in BBd three quarters of the cells were MARK-1+. Therefore, to distinguish the role of T- versus B-cells, enriched T-lymphocyte (CD5+) preparations were studied: glutamate (5.3-fold) and NH3 (4.2-fold) production from glutamine and lactate (1.7-fold) production from glucose were greater (p < 0.05) in cells from BBd rats. This establishes that in BBd cells (i) lymphocytes (especially CD4+) contribute to the increased metabolism, (ii) T-lymphocytes are especially active in glutamine metabolism, but because of their reduced numbers, this cannot fully account for the increase in the unfractionated population, and therefore (iii) B-lymphocytes probably also contribute, and (iv) the altered metabolism of these cells is not a result of the diabetic state. These findings are consistent with activation of immunocytes of multiple lineages in this autoimmune syndrome.Key words: glutamine, glucose, lymphocytes, BB rat.

Myocardial function and energy substrate metabolism in the insulin-resistant JCR:LA corpulent rat

1991 ◽  
Vol 71 (4) ◽  
pp. 1302-1308 ◽  
Author(s):  
G. D. Lopaschuk ◽  
J. C. Russell
Keyword(s):  
Contractile Function ◽  
Substrate Utilization ◽  
Diabetic Rats ◽  
Energy Substrate ◽  
Atp Production ◽  
Insulin Resistant ◽  
Oxidation Rates ◽  
Lean Control ◽  
Insulin Dependent ◽  
And Control

Alterations in myocardial energy substrate utilization contribute to the development of cardiomyopathic changes in insulin-dependent and non-insulin-dependent diabetic rats. Energy substrate utilization and contractile function, however, have not been characterized in insulin-resistant diabetes. In this study, we studied these parameters in the insulin-resistant obese JCR:LA-cp rat homozygous for the corpulent gene (cp/cp). Homozygous (+/+) or heterozygous (+/cp) lean non-insulin-resistant rats were used as controls. Isolated working hearts from cp/cp and lean control rats were perfused with Krebs-Henseleit buffer containing either 11 mM [U-14C]glucose and 0.4 mM palmitate or 11 mM glucose and 0.4 mM [1–14C]palmitate. Unlike control hearts, hearts from cp/cp rats were found to require high doses of insulin and Ca2+ concentrations of less than or equal to 1.75 mM to maintain mechanical function. In the presence of 2,000 microU/ml insulin, contractile function from cp/cp rat hearts was not depressed in the presence of either 1.25 or 1.75 mM Ca2+. Steady-state glucose oxidation rates in hearts perfused with 1.25 mM Ca2+ and 2,000 microU/ml insulin were 811 +/- 86 (SE) and 612 +/- 51 nmol.min-1.g dry wt-1 in cp/cp and control rats, respectively. Palmitate oxidation was 307 +/- 47 and 307 +/- 47 nmol.min-1.g dry wt-1 in cp/cp and lean control hearts, respectively. Under these perfusion conditions, 40% of myocardial ATP production was derived from glucose, whereas 60% was derived from palmitate in both cp/cp and control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Genetic analysis of the BB/W diabetic rat

1983 ◽  
Vol 25 (1) ◽  
pp. 7-15 ◽  
Author(s):  
L. Butler ◽  
D. L. Guberski ◽  
A. A. Like
Keyword(s):  
Gene Cluster ◽  
Recessive Gene ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Large Colony ◽  
Insulin Dependent ◽  
Inheritance Of Diabetes ◽  
Or Gene ◽  
Normal Offspring ◽  
Foundation Stock

A large colony of BB/W diabetic rats has been developed as a research model for insulin dependent, type 1 diabetes mellitus. The foundation stock had 8% diabetics which appeared in a sporadic manner. The Worcester (W) colony was inbred by brother × sister matings for 11 generations and the proportion of diabetics increased to over 50%. The age of detection varies from 46 to 250 days. For selection purposes, classification was made at 120 days, which means that 15 to 20% potential diabetics were classified as normal. Evidence from different analyses indicates that the inheritance of diabetes is by a recessive gene or gene cluster with 50% penetrance at 120 days. The selection of breeding stock from diabetic parents raised the proportion of diabetics produced by two normal parents from 12 to 43%. Diallel tests show that diabetic and normal offspring of two diabetic parents have the same diabetic gentoype. Outcrosses to other strains of rat indicate that the trait is transferred as a recessive with only 3% diabetics recovered in the F2 where noninbred BB stock was used as the diabetic source, and 36% where partially inbred BB/W was used as the diabetic parent. Since the proportion of diabetics produced by all types of crosses has changed, and may continue to change with changes in the genetic background, we have used the operational term penetrance to describe the frequency of diabetes in individuals homozygous for the diabetes gene cluster. At present the penetrance at 120 days is 59% in the BB/W colony.

Triacylglycerol turnover in isolated working hearts of acutely diabetic rats

1994 ◽  
Vol 72 (10) ◽  
pp. 1110-1119 ◽  
Author(s):  
Maruf Saddik ◽  
Gary D. Lopaschuk
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Glucose Oxidation ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Acid Oxidation ◽  
Atp Production ◽  
Oxidation Rates ◽  
Rat Hearts

Although myocardial triacylglycerol may be a potentially important source of fatty acids for β-oxidation in diabetes, few studies have measured triacylglycerol turnover directly in hearts from diabetic animals. In this study, myocardial triacylglycerol turnover was directly measured in isolated working hearts from streptozotocin-induced acutely diabetic rats. Hearts were initially perfused in the presence of 1.2 mM [14C]palmitate and 11 mM glucose for 1 h (pulse) to label the endogenous lipid pools, followed by a 10-min washout perfusion. Hearts were then perfused for another hour (chase) with buffer containing 11 mM glucose ± 1.2 mM [3H]palmitate. During the chase, both 14CO2 and 3H2O production (measures of endogenous and exogenous fatty acid oxidation, respectively) were determined. A second series of hearts were perfused using the same protocol, except that unlabeled palmitate was used during the pulse and 11 mM [14C(U),5-3H]glucose ± unlabeled palmitate was present during the chase. Both glycolysis (3H2O production) and glucose oxidation (14CO2 production) rates were measured in this series. Myocardial triacylglycerol levels were significantly higher in the diabetic rat hearts (77.5 ± 4.6 vs. 33.7 ± 4.1 μmol fatty acid/g dry mass in control hearts). In diabetic rat hearts chased with 1.2 mM palmitate, triacylglycerol lipolysis was increased, although endogenous [14C]palmitate oxidation rates were similar to control hearts and contributed 10.1% of overall ATP production. The majority of fatty acids derived from triacylglycerol lipolysis were released into the perfusate. In the absence of palmitate, both triacylglycerol lipolysis and endogenous [14C]palmitate oxidation rates were significantly increased in diabetic rat hearts, compared with control. Under these conditions, triacylglycerol fatty acid oxidation contributed 70% of steady-state ATP production in diabetic rat hearts, compared with 34% in control hearts. These results demonstrate that in diabetic rat hearts myocardial triacylglycerol lipolysis is significantly increased and can readily be used as a source of fatty acids for mitochondrial β-oxidation.Key words: heart, triacylglycerols, fatty acid oxidation, glucose oxidation, glycolysis.

Mitochondrial dysfunction accompanies diastolic dysfunction in diabetic rat heart

1996 ◽  
Vol 271 (1) ◽  
pp. H192-H202 ◽  
Author(s):  
C. E. Flarsheim ◽  
I. L. Grupp ◽  
M. A. Matlib
Keyword(s):  
Atp Synthesis ◽  
Insulin Dependent Diabetes Mellitus ◽  
Work Load ◽  
Diabetic Rats ◽  
Dependent Diabetes Mellitus ◽  
Diabetic Rat ◽  
Synthesis Rate ◽  
Insulin Dependent ◽  
And Control ◽  
Stimulation Of

The objective of this study was to determine whether a defect in mitochondrial respiratory function accompanies the development of diabetic cardiomyopathy. The hypothesis tested in this study is that a decrease in Ca2+ uptake into mitochondria may prevent the stimulation of Ca(2+)-sensitive matrix dehydrogenases and the rate of ATP synthesis. Streptozotocin (55 mg/kg)-induced diabetic rats were used as a model of insulin-dependent diabetes mellitus. Hearts from 4-wk diabetic rats had basal heart rates and rates of contraction and relaxation similar to control. Isoproterenol caused a similar increase in the rate of contraction in diabetic and control hearts, whereas the peak rate of relaxation was reduced in diabetic hearts. Mitochondrial Ca2+ uptake was reduced in mitochondria from diabetic hearts after 2 wk of diabetes. Na(+)-induced Ca2+ release was unchanged. State 3 respiration rate was depressed in mitochondria from diabetic rats only when the respiration was supported by the substrate of a Ca(2+)-regulated matrix enzyme. The pyruvate dehydrogenase activity was reduced in diabetic mitochondria compared with that of control. It was concluded that mitochondria from diabetic hearts had a decreased capacity to upregulate ATP synthesis via stimulation of Ca(2+)-sensitive matrix dehydrogenases. The impairment in the augmentation of ATP synthesis rate accompanies a decreased rate of relaxation during increased work load.

Nitric oxide mediates increased prostaglandin E production by oocyte - cumulus complexes in the non-insulin-dependent diabetic rat

1998 ◽  
Vol 10 (2) ◽  
pp. 185 ◽  
Author(s):  
Alicia Jawerbaum ◽  
Elida T. Gonzalez ◽  
Virginia Novaro ◽  
Alicia Faletti ◽  
Martha A. F. Gimeno
Keyword(s):  
Nitric Oxide ◽  
Diabetic Rats ◽  
No Synthase ◽  
Diabetic Rat ◽  
Prostaglandin E ◽  
Basal Secretion ◽  
No Donors ◽  
Insulin Dependent ◽  
Insulin Dependent Diabetic ◽  
Synthase Inhibitor

Previous work described an increase in prostaglandin E (PGE) production by oocyte–cumulus complexes (OVA) obtained from non-insulin-dependent diabetic rats. More recently, it has been found that in control OVA nitric oxide (NO) mediates hCG-induced PGE secretion. To determine whether increases in PGE secretion by diabetic OVA are mediated by NO, the present study has evaluated the secretion of PGE by diabetic OVA, cultured in the absence or presence of hCG, NO donors (sodium nitroprusside (NP) and 3-morpholino-sydnonimine-hydrochloride (SIN–1)), and a NO synthase inhibitor (NG monomethyl-L-arginine; L-NMMA). hCG, NP and SIN–1 increased PGE secretion by diabetic OVA. L-NMMA did not modify basal secretion of PGE by control OVA but lowered PGE production in diabetic OVA to control values. L-NMMA prevented the hCG-induced PGE accumulation in control and diabetic OVA, and the quantities of PGE produced were similar to those of control OVA but lower than in diabetic OVA incubated in the absence of hCG. The effect of L-NMMA seems to be specific since NG monomethyl-D-arginine had no effect. NO synthase activity was higher in diabetic ovaries than in controls. The present results suggest that NO mediates the increased PGE production by diabetic OVA, probably a result of overproduction of NO.

Glutamine and glucose metabolism in thymocytes from normal and spontaneously diabetic BB rats

1991 ◽  
Vol 69 (12) ◽  
pp. 801-808 ◽  
Author(s):  
Guoyao Wu ◽  
Catherine J. Field ◽  
Errol B. Marliss
Keyword(s):  
Energy Metabolism ◽  
Krebs Cycle ◽  
Major Product ◽  
Lymphoid Organs ◽  
Glutamine Metabolism ◽  
Potential Production ◽  
Atp Production ◽  
Bb Rats ◽  
Oxidation Of Glucose ◽  
Diabetic Syndrome

Metabolism of glutamine and glucose was studied in thymocytes from normal rats and BB rats with the spontaneous autoimmune diabetic syndrome to assess their potential roles as fuels. The major measured products from glucose were lactate and, to a lesser extent, CO2, and pyruvate. Glutamine had no effect on the rates of their production from glucose. Glutamine was metabolized to ammonia, aspartate, glutamate, and CO2, with aspartate being the major product of carbons from glutamine in the absence of glucose. Glucose markedly decreased the formation of ammonia, aspartate, and CO2 from glutamine, but increased that of glutamate, with an overall decrease in glutamine utilization by 55%. More glutamate than aspartate was produced from glutamine in the presence of glucose. The potential production of ATP from glucose was similar to that when glutamine was present alone. However, glucose markedly decreased production of ATP from glutamine, but not vice versa. This resulted in ATP production from glucose being 2.5 times that from glutamine when both substrates were present. The oxidation of glucose to CO2 via the Krebs cycle accounts for 75–80% of glucose-derived ATP production. Cellular ATP levels markedly decreased in the absence of exogenous substrates, but were constant throughout a 2-h incubation in the presence of glutamine, glucose, or both. There were no differences in thymocyte glucose or glutamine metabolism between normal and diabetic BB rats, in contrast to previous findings in peripheral lymphoid organs. Our results suggest that glucose is a more important fuel than glutamine for "resting" thymocytes, again in contrast to the cells of peripheral lymphoid organs in which glutamine is as important as glucose as a fuel. The enhanced energy metabolism found in the cells from peripheral lymphoid organs of diabetic BB rats, if due to T-lymphocytes, must occur after their migration out of the thymus.Key words: glutaminolysis, glycolysis, thymocytes, ATP, BB rats.

Timed interruption of insulin therapy in diabetic BB/E rat pregnancy: effect on maternal metabolism and fetal outcome

1989 ◽  
Vol 120 (6) ◽  
pp. 800-810 ◽  
Author(s):  
U. J. Eriksson ◽  
A. J. Bone ◽  
D. M. Turnbull ◽  
J. D. Baird
Keyword(s):  
Adverse Effect ◽  
Death Rate ◽  
Skeletal Development ◽  
Fetal Outcome ◽  
Diabetic Rats ◽  
Bb Rat ◽  
Withdrawing Treatment ◽  
Pancreatic Insulin ◽  
Maternal Metabolism ◽  
Insulin Dependent

Abstract. Experimental and clinical studies have suggested that periods of poor metabolic control in early diabetic pregnancy have an adverse effect on the developing embryo, but the precise nature and mechanism of this damaging influence have not been defined. In this study the effect of withdrawing treatment with insulin for 2 days at various times during early gestation on maternal metabolism and fetal outcome has been investigated in the spontaneously diabetic BB/E rat. Nondiabetic BB/E rats and diabetic BB/E rats treated continuously with insulin throughout pregnancy served as controls. Continuously treated diabetic rats had a higher rate of fetal resorption and bigger placentae and their offspring had fewer ossification centres, lower extractable pancreatic insulin content, larger hearts, and smaller kidneys and lungs than the offpring of non-diabetic rats. Interruption of treatment with insulin further aggravated the adverse effect of diabetes on the outcome of pregnancy by resulting in a further increase in the rate of fetal resorption, a rise in the neonatal death rate, a reduction in fetal body weight, and retardation of skeletal development. These effects were more apparent when interruption of treatment with insulin occurred during the period of organogenesis, i.e. during gestational days 8 and 9, and 10 and 11. Two severe malformations were seen, both in litters originating from mothers whose treatment with insulin was interrupted during and immediately before fetal organogenesis. We conclude that a period of disturbed maternal metabolism during fetal organogenesis is capable of affecting the survival, growth, and organ development of the fetus and that the spontaneously diabetic insulin-dependent BB rat appears to be a good model for studies of the effect of diabetes and its treatment on the outcome of pregnancy.

scholarly journals The regulation of glutamine and ketone-body metabolism in the small intestine of the long-term (40-day) streptozotocin-diabetic rat

1987 ◽  
Vol 242 (1) ◽  
pp. 61-68 ◽  
Author(s):  
M Watford ◽  
E J Erbelding ◽  
E M Smith
Keyword(s):  
Small Intestine ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Streptozotocin Diabetes ◽  
Diabetic Rats ◽  
Glutamine Metabolism ◽  
Diabetic Rat ◽  
Coa Transferase ◽  
Glutaminase Activity

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.

Anti-diabetic activity of diphenhydramine in diabetic rats

2020 ◽  
Vol 11 (4) ◽  
pp. 5067-5070
Author(s):  
Pang Jyh Chayng ◽  
Nurul Ain ◽  
Kaswandi Md Ambia ◽  
Rahim Md Noah
Keyword(s):  
Blood Glucose ◽  
Blood Glucose Level ◽  
Glucose Level ◽  
Fasting Blood Glucose ◽  
Insulin Level ◽  
Diabetic Rats ◽  
Group Iv ◽  
Diabetic Rat ◽  
Control Group ◽  
Group I

The purpose of this project is to study the anti-diabetic effect of on a diabetic rat model. A total of Twenty male Sprague rats were used and it randomly distributed into four groups which are Group I: , Group II: negative control, Group III: and Group IV: and . In diabetic model were induced with via injection at the dosage of 65mg/kg. and FBG (Fasting Blood Glucose) level of diabetic rats were assessed every three days. Blood was collected via cardiac puncture at day 21 after the induction of treatment. Insulin level of the rats was assessed with the Mercodia Rat Insulin ELISA kit. FBG level of group I (12.16 ±3.96, p&lt;0.05) and group IV (11.34 ±3.67, p&lt;0.05) were significantly decreased. Meanwhile, the for all rats did not show any significant increase. However, the insulin level was escalated in group IV (0.74+0.25, p&lt;0.05) significantly. The present study shows that the and the combination of and lowered blood glucose level and enhanced insulin secretion.

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