scholarly journals Na/K-ATPase Activity and Ketone Body Metabolism in Long-term Diabetic Rats

2019 ◽  
Author(s):  
Engelbert Buxbaum
Keyword(s):  
Atpase Activity ◽  
Sodium Pump ◽  
Ketone Bodies ◽  
Diabetic Rats ◽  
Hydroxybutyric Acid ◽  
Short Term ◽  
Kinase C ◽  
Streptozotocin Induced Diabetes ◽  
Phosphate Buffered Saline

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)

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
Keyword(s):  
Small Intestine ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Diabetic Rats ◽  
Glutamine Metabolism ◽  
Gut Mucosa ◽  
Streptozotocin Induced Diabetes ◽  
Streptozotocin Diabetic Rats ◽  
Short And Long Term

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.

Calcium homeostasis in chronic streptozotocin-induced diabetes mellitus in the rat

1982 ◽  
Vol 242 (6) ◽  
pp. E451-E456 ◽  
Author(s):  
S. Hough ◽  
J. E. Russell ◽  
S. L. Teitelbaum ◽  
L. V. Avioli
Keyword(s):  
Insulin Therapy ◽  
Calcium Homeostasis ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Calcium Balance ◽  
Short Term ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Streptozotocin Induced Diabetes

Calcium homeostasis was studied in freely fed control, streptozotocin diabetic, long-term and short-term insulin-treated diabetic rats 7 wk after the induction of diabetes. In contrast to the short-term (5-12 day) diabetic rat model, intestinal absorption of calcium was markedly enhanced in chronically insulin-deficient animals. Moreover, conventional balance studies showed that these animals were in positive calcium balance despite severe hypercalciuria. Intestinal hyperabsorption of calcium in long-standing diabetic rats occurred despite low levels of circulating 1,25-dihydroxyvitamin D and hypercorticosteronism and was attended by hypercalcemia and suppression of both plasma parathyroid hormone (PTH) and urinary cyclic 3',5'-AMP (cAMP). Long-term insulin replacement completely normalized the intestinal hyperabsorption of calcium, corrected the plasma calcium, and significantly increased circulating PTH and urinary cAMP excretion. Insulin therapy also corrected the decreased plasma 1,25-dihydroxyvitamin D observed in untreated diabetic animals. Intestinal hyperabsorption of calcium appeared to be only partially corrected by short-term insulin therapy. The accumulated results reveal decided differences in calcium homeostasis and hormonal response between the rats with long-standing diabetes and those with diabetes of short duration.

Down-regulation of protein kinase C and kinase inhibitors dissociate short- and long-term enhancement produced by one-trial conditioning of Hermissenda

1993 ◽  
Vol 69 (2) ◽  
pp. 636-641 ◽  
Author(s):  
T. Crow ◽  
J. Forrester
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Kinase Inhibitors ◽  
Protein Kinase Inhibitors ◽  
Cellular Plasticity ◽  
Short Term ◽  
Down Regulation ◽  
Kinase C ◽  
Short And Long Term

1. The visual system of Hermissenda has been studied extensively as a site of cellular plasticity produced by classical conditioning. Previous research has shown that one-trial conditioning, consisting of light paired with serotonin (5-HT) results in short- and long-term enhancement of light-elicited generator potentials in identified type B-photoreceptors. Recent evidence suggests that 5-HT exerts its effects on the induction of short-term enhancement by activation of protein kinase C (PKC), a Ca(2+)-activated and phospholipid-dependent protein kinase. However, the contribution of protein kinases in general, and specifically PKC in long-term enhancement has not been established. 2. The protein kinase inhibitors H-7 and sphingosine blocked the induction of short-term enhancement when applied before one-trial conditioning. However, the conditions that are sufficient to block the induction of short-term enhancement do not block long-term enhancement. Sphingosine and H-7 do not block the induction and expression of long-term enhancement when applied before one-trial conditioning. 3. Pretreatment before conditioning with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), which leads to down-regulation of PKC, also did not block long-term enhancement. Down-regulation by itself did not produce enhancement, although the transient peak of light-elicited generator potentials was reduced by pretreatment with TPA. 4. The results suggest that the induction of short- and long-term enhancement involve parallel processes, and thus the expression of long-term cellular plasticity produced by one-trial conditioning does not depend on the induction or expression of short-term enhancement.

Effect of pancreas transplantation on decreased levels of circulating bone γ-carboxyglutamic acid-containing protein and osteopenia in rats with streptozotocin-induced diabetes

1992 ◽  
Vol 127 (1) ◽  
pp. 81-85 ◽  
Author(s):  
Hitoshi Ishida ◽  
Yutaka Seino ◽  
Noritaka Takeshita ◽  
Takeshi Kurose ◽  
Kazuo Tsuji ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Bone Turnover ◽  
Pancreas Transplantation ◽  
Diabetic Rats ◽  
Chronic Complications ◽  
Carboxyglutamic Acid ◽  
Low Bone Turnover ◽  
Streptozotocin Induced Diabetes ◽  
Diabetic Osteopenia

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.

Short-term effect of aldosterone on NEM-sensitive ATPase in rat collecting tubule

1989 ◽  
Vol 257 (2) ◽  
pp. F177-F181 ◽  
Author(s):  
C. Khadouri ◽  
S. Marsy ◽  
C. Barlet-Bas ◽  
A. Doucet
Keyword(s):  
Atpase Activity ◽  
Affinity Constant ◽  
Short Term ◽  
Collecting Tubule ◽  
Lag Period ◽  
In Vitro Effects ◽  
Collecting Tubules

Because previous studies indicated that in the collecting tubule, N-ethylmaleimide (NEM)-sensitive ATPase, the biochemical equivalent of the proton pump, is controlled by mineralocorticoids in the long term, the present study was designed to investigate whether such control also exists in the short term. Therefore we investigated the in vivo and in vitro effects of aldosterone on the enzyme activity in cortical and outer medullary collecting tubules (CCT and MCT, respectively) from adrenalectomized rats. Administration of aldosterone (10 micrograms/kg body wt) markedly stimulated NEM-sensitive ATPase activity in the CCT and MCT within 3 h. Similarly, incubating CCT or MCT for 3 h in the presence of 10(-8) M aldosterone enhanced NEM-sensitive ATPase activity up to values similar to those previously measured in the corresponding nephron segments of normal rats. In vitro stimulation of NEM-sensitive ATPase was dose dependent in regard to aldosterone (apparent affinity constant approximately 10(-9) M), appeared after a 30-min lag period, and reached its maximum after 2-2.5 h. Finally, actinomycin D and cycloheximide totally abolished the in vitro action of aldosterone, demonstrating the involvement of protein synthesis in this process.

Drug inhibition of memory formation in chickens II. Short-term memory

1971 ◽  
Vol 178 (1053) ◽  
pp. 455-464 ◽  
Keyword(s):  
Protein Synthesis ◽  
Sodium Pump ◽  
Short Term Memory ◽  
Memory Loss ◽  
Protein Synthesis Inhibitor ◽  
Protein Synthesis Inhibitors ◽  
Short Term ◽  
Synthesis Inhibitor ◽  
Term Memory

1. Memory in day-old-chickens during the first few hours after learning can be made to decline by the prior intracranial injection of two classes of drugs. 2. Sodium pump inhibitors in increasing doses cause increasingly rapid loss of memory. 3. Protein synthesis inhibitors in increasing doses attain a maximum potency in causing memory decline and the rate may not be further accelerated by higher doses. 4. Adding a sodium pump inhibitor to the inhibition of protein synthesis increases memory loss. 5. Adding a protein synthesis inhibitor to a sodium pump inhibitor causes no further loss. 6. Therefore within a few minutes of learning a short-term memory of limited time span but independent of protein synthesis becomes supplemented and eventually replaced by a long-term storage requiring protein synthesis. The amount of long-term store is set by the amount of short-term memory. 7. The short-term store could be directly dependent on post-activation enhancement of Na + extrusion from neurons. Some physiological mechanisms by which this could be achieved and how this might activate protein synthesis are discussed.

In vitro pituitary GH secretion after GHRH, forskolin, dibutyryl cyclic-adenosine 3′,5′-monophosphate and phorbol 12-myristate 13-acetate stimulation in long-term orchidectomized rats

1996 ◽  
Vol 16 (1) ◽  
pp. 81-88 ◽  
Author(s):  
M Tena-Sempere ◽  
L Pinilla ◽  
E Aguilar
Keyword(s):  
Male Rats ◽  
Short Term ◽  
Compensatory Mechanisms ◽  
Gh Secretion ◽  
Camp Pathway ◽  
Kinase C ◽  
High Doses

ABSTRACT In the present work in vitro GH pituitary responsiveness to GHRH in short-term (STO) and long-term orchidectomized (LTO) male rats was compared. In agreement with previous data obtained in vivo, pituitaries from STO rats showed reduced GH release after GHRH stimulation while LTO male pituitaries presented responses similar to those from control animals after maximal GHRH (10-6 m) stimulation. This suggests that compensatory mechanisms have taken place, probably at the pituitary level, in order to restore GH pituitary responsiveness to high doses of GHRH. However, LTO male rats showed a reduced sensitivity to GHRH relative to intact males, as indicated by a higher EC50 vs controls (40·82 ± 12·03 nm vs 0·35 ± 0·09 nm in intact males). We aimed to investigate further the events involved in the compensatory mechanisms that take place in LTO rats. For this purpose, we compared in vitro GH secretion by pituitaries from intact and LTO male rats after stimulation with specific activators of the signal transduction pathways related to GH release. Forskolin and dibutyryl cyclic-adenosine 3′,5′-monophosphate were more effective in eliciting GH secretion (expressed in terms of percent increment over basal GH release) in LTO males, whereas phorbol 12-myristate 13-acetate was completely ineffective in stimulating GH release in this group. Thus, our results clearly showed that long-term orchidectomy enhances the effectiveness of the cAMP pathway in inducing GH release while it completely blunts that of the protein kinase C pathway. In conclusion, orchidectomy decreased the effectiveness of GHRH in eliciting GH release in vitro. However, long-term orchidectomy activated compensatory mechanisms that restored complete GH pituitary responsiveness to maximal GHRH stimulation. These mechanisms seem not to operate in STO rats. An increased effectiveness of the cAMP pathway in eliciting GH release in LTO rats is probably involved in the aforementioned compensatory mechanisms.

Glucocorticoids and insulin: reciprocal signals for energy balance

1995 ◽  
Vol 268 (1) ◽  
pp. R142-R149 ◽  
Author(s):  
A. M. Strack ◽  
R. J. Sebastian ◽  
M. W. Schwartz ◽  
M. F. Dallman
Keyword(s):  
Body Weight ◽  
Energy Balance ◽  
Food Intake ◽  
Diabetic Rats ◽  
Energy Gain ◽  
Energy Stores ◽  
The Central Nervous System ◽  
Streptozotocin Induced Diabetes ◽  
Term Energy

Signals that regulate long-term energy balance have been difficult to identify. Increasingly strong evidence indicates that insulin, acting on the central nervous system in part through its effect on neuropeptide Y (NPY), inhibits food intake. We hypothesized that corticosteroids and insulin might serve as interacting, reciprocal signals for energy balance, acting on energy acquisition, in part through their effects on hypothalamic NPY, as well as on energy stores. Because glucocorticoids also stimulate insulin secretion, their role is normally obscured. Glucocorticoids and insulin were clamped in adrenalectomized rats with steroid replacement and streptozotocin-induced diabetes. Glucocorticoids stimulated and insulin inhibited NPY mRNA and food intake. Glucocorticoids inhibited and insulin increased energy gain as determined by the change in body weight. When adrenalectomized diabetic rats were treated, corticosterone stimulated and insulin inhibited food intake, and, respectively, inhibited and increased overall energy gain. More than 50% of the variance was explained by regression analysis of the two hormones on food intake and body weight. Thus glucocorticoids and insulin are major, antagonistic, long-term regulators of energy balance. The effects of corticosterone and insulin on food intake may be mediated, in part, through regulation of hypothalamic NPY synthesis and secretion.

scholarly journals Effect of long-term hyperglycemia on cornea and retina morphology in rats with streptozotocin-induced diabetes mellitus

2021 ◽  
pp. 42-47
Author(s):  
А.А. Панов ◽  
Е.М. Ржавина ◽  
М.П. Морозова ◽  
А.К. Ердяков ◽  
С.А. Гаврилова
Keyword(s):  
Diabetes Mellitus ◽  
Ketone Bodies ◽  
Morphological Changes ◽  
Posterior Part ◽  
Male Rats ◽  
Control Group ◽  
Blood Concentrations ◽  
Central Retina ◽  
Streptozotocin Induced Diabetes

Цель исследования - изучение динамики морфологических изменений роговицы и заднего отдела глаза крыс при длительной гипергликемии. Методика. Исследование выполнено на 36 самцах крыс Wistar. Сахарный диабет индуцировали внутрибрюшинной инъекцией стрептозотоцина (65 мг/кг), после чего ежедневно вводили подкожно малые дозы инсулина (2 ЕД/кг). На 50-е, 58-е и 66-е сут эксперимента производили энуклеацию глаз у глубоко наркотизированных животных. Гистологические срезы фрагментов глаз окрашивали гематоксилин-эозином, проводили морфометрию параметров роговицы и сетчатки. Результаты. Средняя концентрация глюкозы и кетоновых тел крови в группе сахарного диабета составила 29,8 ммоль/л и 0,889 ммоль/л, в контрольной группе - 6,2 ммоль/л и 0,847 ммоль/л соответственно. Анализ гистологических срезов глаз выявил признаки отека роговицы, хориоидеи и наружных слоев центральных отделов сетчатки до появления других качественных и количественных морфологических изменений. Заключение. Оценка толщины роговицы, хориоидеи и наружных слоев центральных отделов сетчатки может служить предиктором развития диабетической ретинопатии. The aim was to study morphological changes in the cornea and the posterior part of rat eye during prolonged hyperglycemia. Methods. The study was performed on 36 Wistar male rats. Diabetes mellitus was induced by an injection of streptozotocin (65 mg/kg, i.p.) followed by daily injections of low doses of insulin (2 U/kg, s.c.). Eyes were enucleated from deeply anesthetized rats on days 50, 58, and 66 of the experiment. Histologic sections were stained with hematoxylin-eosin, and morphometry of the cornea and the retina was performed. Results. Mean blood concentrations of glucose and ketone bodies were 29.8 mmol/L and 0.889 mmol/L, respectively, in the diabetic group and 6.2 mmol/L and 0.847 mmol/L, respectively, in the control group. The histological analysis revealed signs of edema in the cornea, choroid and outer layers of the central retina, which preceded other morphological changes. Conclusion. Evaluating thickness of the cornea, choroid and outer layers of the central retina may serve for prediction of diabetic retinopathy.

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