Insulin metabolism by liver, muscle, and kidneys from spontaneously diabetic rats

1986 ◽  
Vol 250 (5) ◽  
pp. E530-E537
Author(s):  
R. Rabkin ◽  
G. M. Reaven ◽  
C. E. Mondon
Keyword(s):  
Diabetic Rats ◽  
Insulin Clearance ◽  
Immunoreactive Insulin ◽  
Insulin Metabolism ◽  
Complex Process ◽  
Consistent Manner ◽  
Liver And Kidney ◽  
Spontaneously Diabetic Rats ◽  
And Control

The in vivo metabolism of insulin is a complex process in which liver, kidney, and muscle are major participants. In this study we evaluated the effect of spontaneous hyperglycemic nonketoacidotic diabetes (DH) and ketoacidotic diabetes (DKA) on insulin clearance and degradation by these organs. Livers, hindlimbs, and kidneys from nondiabetic controls and DH and DKA Bio-Breed rats were isolated and perfused with artificial media. Liver clearance of immunoreactive insulin (ml/min) was significantly higher in DH rats, 6.0 +/- 0.2, but significantly lower in DKA rats, 3.4 +/- 0.5, compared with controls, 4.6 +/- 0.2. Acidosis alone induced by ammonium chloride loading, did not impair liver insulin clearance (4.8 +/- 0.4 ml/min). Muscle responded differently to the diabetic state in that insulin clearance was not altered by DH and DKA. Renal (organ) clearance of insulin was significantly depressed in the DKA state when compared with controls (0.52 +/- 0.04 and 0.75 +/- 0.07 ml X min-1 X g-1, respectively). This could largely be explained by a lower glomerular filtration rate. Fractional urinary insulin clearance was increased twofold above control values in DH kidneys and fourfold in DKA kidneys, indicating that tubular luminal absorption of insulin was impaired in both states. By contrast contraluminal uptake (peritubular clearance) did not differ significantly from controls. 125I-insulin degrading activity of the 100,000 g supernate fraction from muscle homogenates was similar in the diabetic and control groups. However in liver and kidney, degrading activity did not correspond to whole organ insulin clearance in a consistent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Calciotrophic hormones during experimental hypocalcaemia and hypercalcaemia in spontaneously diabetic rats

1999 ◽  
Vol 162 (2) ◽  
pp. 251-258 ◽  
Author(s):  
J Verhaeghe ◽  
R van Bree ◽  
E van Herck ◽  
I Jans ◽  
Z Zaman ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Diabetic Rats ◽  
The Novel ◽  
Insulin Deficiency ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Spontaneously Diabetic Rats ◽  
And Control

1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) concentrations have been found to be decreased in diabetic humans and rats. To investigate further the regulation of plasma Ca in diabetes, first we measured Ca(2+), P, Mg, parathyroid hormone(1-34) (PTH), and total and free 1,25(OH)(2)D(3) in male spontaneously diabetic rats 7 and 28 days after the onset of glycosuria. Secondly, we studied changes in the levels of PTH and 1,25(OH)(2)D(3) in response to hypocalcaemia induced by an i.v. infusion of EGTA (2.5%, wt/vol.) for 24 h, and changes in the levels of 1,25(OH)(2)D(3) in response to an i.v. infusion of rat PTH (10 microgram over 24 h) without or with concomitant EGTA infusion (producing hypercalcaemia or normo/hypocalcaemia respectively), in diabetic and control rats. Ca(2+), P, Mg and PTH concentrations remained within the control ranges after 7 and 28 days of glycosuria; 1,25(OH)(2)D(3) concentrations were decreased after 7, but not after 28, days of glycosuria. PTH concentrations showed a similar rise during EGTA-induced hypocalcaemia in control and diabetic rats compared with saline-infused rats, whereas 1,25(OH)(2)D(3) concentrations were unchanged in both groups. Total and free 1,25(OH)(2)D(3) levels were comparably (about 3-fold) increased during PTH, but not during combined PTH and EGTA infusion in control and diabetic rats. Total 1, 25(OH)(2)D(3) concentrations were lower in the diabetic groups infused with saline or PTH than in their respective controls, and there was a similar trend in the PTH+EGTA-infused group; free 1, 25(OH)(2)D(3) levels, however, were normal or increased in the diabetic groups, confirming our previous data. The novel finding of this study is that, despite severe insulin deficiency and altered 1, 25(OH)(2)D(3) levels, the in vivo response of PTH levels to hypocalcaemia and the in vivo response of 1,25(OH)(2)D(3) levels to PTH in diabetic rats are comparable with those found in nondiabetic rats.

scholarly journals The Insulin Receptor Mediates Insulin’s Early Plasma Clearance by Liver, Muscle, and Kidney

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 37
Author(s):  
Rick I. Meijer ◽  
Eugene J. Barrett
Keyword(s):  
Insulin Receptor ◽  
Plasma Clearance ◽  
Plasma Insulin ◽  
Insulin Clearance ◽  
Initial Plasma ◽  
Liver And Kidney ◽  
Pre Treatment ◽  
Initial Clearance

The role of the insulin receptor in mediating tissue-specific insulin clearance in vivo has not been reported. Using physiologic insulin doses, we measured the initial clearance rate (first 5 min) of intravenously injected ([125I]TyrA14)-insulin by muscle, liver, and kidney in healthy rats in the presence and absence of the insulin receptor blocker S961. We also tested whether 4 weeks of high-fat diet (HFD) affected the initial rate of insulin clearance. Pre-treatment with S961 for 60 min prior to administering labeled insulin raised plasma ([125I]TyrA14)insulin concentration approximately 5-fold (p < 0.001), demonstrating receptor dependency for plasma insulin clearance. Uptake by muscle (p < 0.01), liver (p < 0.05), and kidney (p < 0.001) were each inhibited by receptor blockade, undoubtedly contributing to the reduced plasma clearance. The initial plasma insulin clearance was not significantly affected by HFD, nor was muscle-specific clearance. However, HFD modestly decreased liver clearance (p = 0.056) while increasing renal clearance by >50% (p < 0.01), suggesting a significant role for renal insulin clearance in limiting the hyperinsulinemia that accompanies HFD. We conclude that the insulin receptor is a major mediator of initial insulin clearance from plasma and for its clearance by liver, kidney, and muscle. HFD feeding increases renal insulin clearance to limit systemic hyperinsulinemia.

Correction: In vivo Evaluation of Anti-Hyperglycemic, Anti-hyperlipidemic and Anti-Oxidant Status of Liver and Kidney of Thymol in STZ-Induced Diabetic Rats

Drug Research ◽  
2018 ◽  
Author(s):  
Bijan Oskouei ◽  
Soheil Abbaspour-Ravasjani ◽  
Seyed Jamal Musavinejad ◽  
Seyed Ahmad Salehzadeh ◽  
Alireza Abdolhosseinzadeh ◽  
...  
Keyword(s):  
Diabetic Rats ◽  
In Vivo Evaluation ◽  
Liver And Kidney ◽  
Anti Oxidant ◽  
Oxidant Status

scholarly journals Evaluation of optimal conditions for arginase activity in streptozotocin induced diabetic rats

2012 ◽  
Vol 50 (No. 2) ◽  
pp. 69-76 ◽  
Author(s):  
M. Erisir ◽  
E. Ercel ◽  
S. Yilmaz ◽  
S. Ozan
Keyword(s):  
Maximal Activity ◽  
Diabetic Rats ◽  
Arginase Activity ◽  
Female Rats ◽  
Kinetic Properties ◽  
Ph Profile ◽  
Optimum Ph ◽  
Liver And Kidney ◽  
And Control ◽  
Assay Conditions

The assay conditions needed to achieve maximal activity of liver and kidney arginase in diabetic and non-diabetic rats were investigated and compared. The physicochemical and kinetic properties of liver arginase in diabetic and control rats were very similar, those of kidney arginase were significantly different. It was found that preincubation temperature (68&deg;C), preincubation period (20 min), optimum pH (10.1) of liver arginase and K<sub>m</sub> (3.2) for its substrate, L-arginine, did not change in diabetic and non-diabetic rats. As a consequence of diabetes, the optimum Mn<sup>2+</sup> concentration for liver arginase only changed from 1 to 2 mM. Although the preincubation temperature and period for activation of kidney arginase in control rats was unnecessary, they were found to be 56&ordm;C and 12 min in diabetic rats. The pH profile of arginase in kidney of diabetic rats was different from that of control rats. The K<sub>m</sub> value (6.7) of arginase for L-arginine in kidney is unchanged in diabetes whereas a marked decrease in V<sub>max</sub> was found. Optimum Mn<sup>2+</sup> concentration (2 mM) for kidney arginase was unchanged in diabetes. The activity of arginase in liver of diabetic animals was higher 1.5 to 1.7 times than that of controls. Diabetes caused an about 53% decrease of arginase activity in kidney of female rats, 26% in that of males. These findings may suggest an idea that encoded arginases by separate gene loci may be affected differently by the pathological and hormonal status.

Influence of Loranthus micranthus on hepatic and renal antioxidant status and impaired glycolytic flux in streptozotocin-induced diabetic rats

2018 ◽  
Vol 29 (5) ◽  
pp. 447-461 ◽  
Author(s):  
Azubuike P. Ebokaiwe ◽  
Omamuyovwi M. Ijomone ◽  
Oscar Edeh ◽  
Ifebunachi Oteh ◽  
David E. Ebuka
Keyword(s):  
Glucose Metabolism ◽  
Antioxidant Status ◽  
Leaf Extract ◽  
Diabetic Rats ◽  
Glycolytic Flux ◽  
Traditional Use ◽  
Metabolism Enzymes ◽  
Liver And Kidney ◽  
Treatment Of Diabetes

Abstract Background The use of Loranthus micranthus in folklore medicine for treatment of diabetes and its associated complications is a common practice around the world. The present study investigated this traditional affirmation by in vivo investigation into the effect of L. micranthus leaf extract on hepatic and renal, oxidative status and glucose metabolism in streptozotocin (STZ)-induced diabetic rats. Methods Diabetes mellitus was induced in adult male Wistar rats by intraperitoneal injection of STZ (60 mg/kg). The diabetic rats were thereafter treated orally once per day with 5 mg/kg gilbenclamide or L. micranthus leaf extract (100 or 200 mg/kg) and monitored for 14 days. Clinical observations, plasma biochemistry, hormonal profile, oxidative stress parameters, glucose metabolism enzymes and histopathologic examination of the liver and kidney were evaluated to monitor treatment-related effects of L. micranthus leaf extract in STZ-induced diabetic rats. Results Loranthus micranthus leaf extract administration significantly ameliorated hyperglycemia-mediated damage by decreasing the blood glucose level (45.9% and 84.7% on days 7 and 14 posttreatment, respectively), enhancing the antioxidant status, inhibiting lipid peroxidation and improving the architecture of the liver and kidney in STZ-induced diabetic rats. Furthermore, intervention of L. micranthus leaf extract restored the liver and kidney function biomarkers and increased the plasma levels of triiodothyronine and thyroxine to normal control in STZ-induced diabetic rats. Conclusions The findings from this investigation provide credible scientific support for the traditional use of L. micranthus leaf extract in the treatment of diabetes and its associated complications.

Uptake of tyrosine and leucine in vivo by brain of diabetic and control rats

1984 ◽  
Vol 247 (5) ◽  
pp. C450-C453 ◽  
Author(s):  
J. T. Brosnan ◽  
R. G. Forsey ◽  
M. E. Brosnan
Keyword(s):  
Amino Acids ◽  
Branched Chain Amino Acids ◽  
Diabetic Rats ◽  
Injection Technique ◽  
Brain Uptake ◽  
Absolute Increase ◽  
Normal Plasma ◽  
Branched Chain ◽  
And Control

The uptake of tyrosine and leucine by brain of control and diabetic rats was examined using the Oldendorf intracarotid injection technique. The brain uptake indexes (BUI) for tyrosine and leucine were identical in diabetic and control rats when the injectate consisted of labeled amino acids in Krebs saline. When the injectate consisted of radioactive amino acids added to plasma from either normal or diabetic rats, there was a decreased BUI for tyrosine from diabetic plasma compared with that from normal plasma. This was evident in both control and diabetic rats. Fractional uptake of leucine was unchanged in all situations. Because leucine level is elevated in plasma of diabetic rats there is an absolute increase in leucine uptake in diabetes. Branched-chain amino acids, added to normal plasma in the concentrations at which they occur in diabetic plasma, inhibited the uptake of tyrosine to the same extent as diabetic plasma did. We conclude that the decreased brain uptake and decreased brain level of tyrosine in diabetes is due to the high circulating levels of branched-chain amino acids and cannot be attributed to intrinsic changes in the blood-brain transporter for large neutral amino acids or to changes in other constituents of plasma.

Exogenous substrate utilization by isolated myocytes from chronically diabetic rats

1983 ◽  
Vol 245 (1) ◽  
pp. C46-C51 ◽  
Author(s):  
V. Chen ◽  
G. J. Bagby ◽  
J. J. Spitzer
Keyword(s):  
Inhibitory Effect ◽  
Diabetic Rats ◽  
Lactate Oxidation ◽  
Palmitate Oxidation ◽  
Exogenous Substrate ◽  
Streptozotocin Induced Diabetes ◽  
And Control ◽  
Effect Of Glucose ◽  
Substrate Concentrations

The effect of chronic streptozotocin-induced diabetes on the utilization of exogenous substrates by freshly isolated, Ca2+-tolerant nonbeating myocytes was investigated. The rates of glucose (5 or 25 mM) and lactate (1 mM) oxidation were significantly reduced in myocytes of diabetic rats, whereas palmitate (0.4 or 1 mM) oxidation was similar to the controls. Glucose oxidation in diabetic (but not in control) and palmitate oxidation in control (but not in diabetic) myocytes were increased by raising the respective substrate concentrations in the medium to levels found in vivo in diabetic rats. Inhibition of glucose and lactate oxidation in the presence of competing substrates were generally similar between control and diabetic myocytes. However, the inhibitory effect of glucose on lactate oxidation was greater in control cells. The rate of palmitate oxidation was diminished by glucose in the controls, but this was not observed in the diabetic myocytes. Oxygen consumption by the myocytes of diabetic rats was below that of control cells when lactate or palmitate was present in the medium. ATP and phosphocreatine contents were similar in the myocytes of diabetic and control rats. All the observed changes in myocytes prepared from diabetic rats were reversed by in vivo insulin treatment.

scholarly journals In vivo and in vitro antidiabetic properties of alkaloids extract from Salvia chudaei

2021 ◽  
pp. 45-53
Author(s):  
Mohammed Tlili ◽  
Roukia Hammoudi ◽  
Mahfoud Hadj-Mahammed
Keyword(s):  
Blood Glucose ◽  
Lipid Profile ◽  
Kidney Function ◽  
Inhibitory Effect ◽  
Diabetic Rats ◽  
Albino Rats ◽  
Liver And Kidney ◽  
Mean Blood Glucose

The aim of this study was to evaluate, for the first time, the antidiabetic effect of the alkaloids extract of Salvia chudaei Batt. & Trab. (Lamiaceae) on alloxan-induced diabetic rats. The alkaloids extract was prepared, and the in vitro inhibitory effect of key digesting enzymes related to postprandial hyperglycemia were determined. After acute toxicity test, the Swiss albino rats were induced with alloxan to get experimental diabetes animals. The fasting mean blood glucose, lipid profile, different liver and kidney function biomarkers and antioxidant biomarkers levels, after treatment for 30 days, diabetic untreated and diabetic rats treated with alkaloids extract were estimated. The alkaloids displayed remarkable in inhibiting ?-glucosidase (IC50 = 248.25?2.61 ?g/ml) than ?-amylase (IC50 = 262.96?9.64 ?g/ml) activities. In vivo, the results proved that alkaloids extract at dose of 500 mg/kg bw decreased significantly the blood glucose, lipid profile levels and improved the liver and kidney function biomarkers and increased the activities of antioxidant enzymes (superoxide dismutase and gluthatione reductase). This study demonstrates, that alkaloids are effective in inhibiting hyperglycemia and oxidative stress caused by diabetes.

The antiadrenergic effect of cyclopentyladenosine on myocardial contractility is reduced in vivo in diabetic rats

1994 ◽  
Vol 72 (10) ◽  
pp. 1245-1251 ◽  
Author(s):  
Fred D. Romano ◽  
Stephen J. Kopp ◽  
June T. Daar ◽  
Cynthia A. Smith
Keyword(s):  
Insulin Treatment ◽  
Left Ventricular Pressure ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Adrenergic Agonist ◽  
Experimental Diabetes Mellitus ◽  
Ventricular Performance ◽  
And Control ◽  
Dose Dependent

The aim of this study was to test the hypothesis that the antiadrenergic action of adenosine is reduced in diabetes. This was determined by evaluating the effect of experimental diabetes mellitus on the in vivo myocardial antiadrenergic action of cyclopentyladenosine, an adenosine A1- receptor agonist. Changes in heart rate and ventricular performance in response to infusion of dobutamine, a β1-adrenergic agonist, were determined in the absence and presence of cyclopentyladenosine, in anesthetized, 10- to 12-week male diabetic (60 mg/kg streptozotocin), insulin-treated diabetic and control rats. Intravenous dobutamine (16 μg/kg) increased +dP/dtmax and −dP/dtmax in control rats from 7 706 ± 553 and 5 449 ± 403 mmHg/s (1 mmHg = 133.3 Pa) to 19 170 ± 465 and 8 855 ± 317 mmHg/s, respectively. In diabetic rats dobutamine increased +dP/dtmax and −dP/dtmax from 5 733 ± 541 and 4 016 ± 426 to 15 015 ± 1 521 and 7 039 ± 809 mmHg/s, respectively. Cyclopentyladenosine significantly attenuated dobutamine-stimulated increases in +dP/dtmax and −dP/dtmax in both control and diabetic rats in a dose-dependent (0.1–3.0 μg/kg) manner. Cyclopentyladenosine potency to attenuate dobutamine-enhanced +dP/dtmax was reduced significantly (p < 0.05) in diabetic rats compared with controls (ID50, 1.07 vs. 0.59 μg/kg, respectively) with no change in efficacy. The magnitude of cyclopentyladenosine inhibition of dobutamine-enhanced −dP/dtmax was greater in control than diabetic rats (81 vs. 54%, respectively), but ID50 values were not different. Insulin treatment of diabetic rats prevented the observed changes. These data suggest that the antiadrenergic action of adenosine is compromised in diabetes and that this may contribute to the development of diabetic cardiomyopathy.Key words: adenosine, dobutamine, ventricle, left ventricular pressure, streptozotocin.

Platelet Abnormalities in Experimental Diabetes

1979 ◽  
Author(s):  
M. Johnson ◽  
H.E. Harrison ◽  
R. Hawker ◽  
L. Hawker
Keyword(s):  
Platelet Function ◽  
Experimental Diabetes ◽  
Platelet Reactivity ◽  
Vascular Complications ◽  
Diabetic Rats ◽  
Thromboxane Synthetase ◽  
Patients With Diabetes ◽  
Streptozotocin Diabetic Rats ◽  
And Control

Many abnormalities of platelet function occur in patients with diabetes mellitus, partioularly those with angiopathy. We have previously demonstrated that prostacyclin (PGI2) is decreased in streptozotocin-diabetic rats, and have now investigated platelet reactivity in these animals. Responsiveness to ADP and arachidonlc acid was increased, and platelet cyclo-oxygenase and thromboxane synthetase activities were significantly elevated (p<0.05) in diabetic animals (5.5±0.7 and 5.9±0.9 arbitrary units/109 platelets) when compared with control animals (J.0±0.4 and 3.9±0.3 arbitrary units/109 platelets). Malondialdehyde synthesis was 1,5 and 0.9 n moles per 108 platelets in diabetic and control rats respectively. Diabetic platelets were also less sensitive to the anti-aggregating effects of PGI2 (IC50: diabetic, 2.3 ng/ml; control, 1.3 ng/ml. Survival of illindium-labelled autologous platelets was significantly reduced, indicating that platelet function is abnormal in vivo, in diabetic animals. Platelet hyper-reactivity, possibly associated with depressed PGI2, could be related to the vascular complications of diabetes.

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