Alterations induced by alloxan-diabetes and starvation on functional activity of the rat portal vein perfused in vitro

1980 ◽  
Vol 58 (6) ◽  
pp. 731-737 ◽  
Author(s):  
M. Fiol de Cuneo ◽  
M. G. Cremer-Lacuara ◽  
R. D. Ruiz ◽  
J. L. Lacuara
Keyword(s):  
Alloxan Diabetes ◽  
Experimental Diabetes ◽  
Aerobic Glycolysis ◽  
Diabetic Rats ◽  
Glycerol Production ◽  
Fatty Acid Utilization ◽  
Rat Portal Vein ◽  
Portal Veins ◽  
Contractile Recovery

The levels of isometric developed tension (IDT) in portal veins from starved and diabetic rats in glucose medium were of the same magnitude but significantly reduced compared with veins from normal rats. Glucose removal led to contractile depression, more marked in starved veins (−74%; p < 0.001 vs. diabetics and normals). Addition of glucose, pyruvate, acetate, lactate, or butyrate counteracted this depression in all groups but in diabetics butyrate significantly stimulated IDT over controls whereas in starved veins lactate overcame IDT reduction only partially.Added insulin significantly enhanced contractile recovery with glucose in normal and diabetic preparations but was ineffective in starved veins.Glycogen content was significantly lower in diabetics; however, in no group did changes occur in incubated veins as compared with unincubated ones. Glycerol production was significantly higher in diabetic veins.It would appear that, although experimental diabetes induces a shift to fatty acid utilization, aerobic glycolysis and mitochondrial respiration are somehow preserved as reflected by the IDT recovery with pyruvate or lactate.

scholarly journals Alendronate Can Improve Bone Alterations in Experimental Diabetes by Preventing Antiosteogenic, Antichondrogenic, and Proadipocytic Effects of AGEs on Bone Marrow Progenitor Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Sara Rocío Chuguransky ◽  
Ana María Cortizo ◽  
Antonio Desmond McCarthy
Keyword(s):  
Bone Marrow ◽  
Experimental Diabetes ◽  
Bone Microarchitecture ◽  
Bone Matrix ◽  
Diabetic Rats ◽  
Long Bone ◽  
Osteogenic Potential ◽  
Bone Marrow Progenitor

Bisphosphonates such as alendronate are antiosteoporotic drugs that inhibit the activity of bone-resorbing osteoclasts and secondarily promote osteoblastic function. Diabetes increases bone-matrix-associated advanced glycation end products (AGEs) that impair bone marrow progenitor cell (BMPC) osteogenic potential and decrease bone quality. Here we investigated the in vitro effect of alendronate and/or AGEs on the osteoblastogenic, adipogenic, and chondrogenic potential of BMPC isolated from nondiabetic untreated rats. We also evaluated the in vivo effect of alendronate (administered orally to rats with insulin-deficient Diabetes) on long-bone microarchitecture and BMPC multilineage potential. In vitro, the osteogenesis (Runx2, alkaline phosphatase, type 1 collagen, and mineralization) and chondrogenesis (glycosaminoglycan production) of BMPC were both decreased by AGEs, while coincubation with alendronate prevented these effects. The adipogenesis of BMPC (PPARγ, intracellular triglycerides, and lipase) was increased by AGEs, and this was prevented by coincubation with alendronate. In vivo, experimental Diabetes (a) decreased femoral trabecular bone area, osteocyte density, and osteoclastic TRAP activity; (b) increased bone marrow adiposity; and (c) deregulated BMPC phenotypic potential (increasing adipogenesis and decreasing osteogenesis and chondrogenesis). Orally administered alendronate prevented all these Diabetes-induced effects on bone. Thus, alendronate could improve bone alterations in diabetic rats by preventing the antiosteogenic, antichondrogenic, and proadipocytic effects of AGEs on BMPC.

scholarly journals THE EFFECT OF INSULIN, ALLOXAN DIABETES, AND ANOXIA ON THE ULTRASTRUCTURE OF THE RAT HEART

1962 ◽  
Vol 15 (3) ◽  
pp. 509-523 ◽  
Author(s):  
David N. Orth ◽  
Howard E. Morgan
Keyword(s):  
Electron Microscopy ◽  
Glucose Transport ◽  
Alloxan Diabetes ◽  
Diabetic Rats ◽  
Cytoplasmic Vesicles ◽  
Lipid Inclusions ◽  
Line Level ◽  
Relationship Of ◽  
The Relationship

Hearts from normal and alloxan diabetic rats were perfused in vitro with a bicarbonate-buffered medium containing glucose. Transport of glucose through the cell membrane was stimulated with insulin or by induction of anaerobiosis. The organs were rapidly fixed and examined by electron microscopy. Transport stimulation was not associated with any increase in the number of sarcolemmal invaginations or subsarcolemmal cytoplasmic vesicles. It was concluded that glucose transport and the effects of insulin or anoxia do not involve pinocytosis. The relationship of pinocytosis to glucose transport is discussed. The appearance of numerous lipid inclusions at the Z line level of the sarcomeres in the diabetic and anoxic myocardia is described.

scholarly journals Neuroendocrine control of the pituitary gonadotropic function in experimental diabetes

2019 ◽  
Vol 43 (3) ◽  
pp. 43-47
Author(s):  
V. N. Babichev ◽  
E. I. Adamskaya ◽  
T. A. Kuznetsova ◽  
I. V. Shishkina
Keyword(s):  
Nuclear Receptors ◽  
Experimental Diabetes ◽  
Diabetic Rats ◽  
Female Rats ◽  
Maximal Response ◽  
Basal Secretion ◽  
Male And Female Rats ◽  
Lh Rh ◽  
Lh Secretion

The hypothalamo-pituitary-gonadal system was examined in male and female rats with experimental diabetes in­duced by streptozotocin (STZ). Injection of STZ caused a decrease of testosterone (T) concentration and of T nuclear receptors in the pituitary. The levels of luteinizing and follicle stimulating hor­mones (LH and FSH) in the blood of diabetic rats did not differ from those in intact animals. In vitro experiments showed that the development of diabetes did not change the basal secretion of LH by the pituitary in males. Maximal response to LH-RH was record­ed in control males after 3-hour incubation, whereas the rate of LH secretion in experimental rats did not differ from basal values. In­jection of STZ to cycling females disordered the estrous cycle and involved decreases of the basal and cyclic secretion of LH, FSH, and sex hormones. The concentrations of estradiol nuclear receptors in the preoptic anterohypothalamic region and pituitary decreased, whereas the number of T-binding sites decreased only in the pitui­tary. Sex hormone-stimulated gonadotropin wave in oophorect- omized females was decreased in diabetes, which was due to changed activity of the LH-RH producing system. The authors hy­pothesize that changes in the mechanism of regulation of the hy­pothalamo-pituitary-gonadal system in experimental diabetes are re­lated to pituitary disorders in males, whereas changed basal and cy­clic secretion of LH and FSH in females is caused by disordered activity of the LH-RH production and receptor binding at the level of the hypothalamo-pituitary complex.

The influence of chronic experimental diabetes on contractile responses of rat isolated blood vessels

1985 ◽  
Vol 63 (1) ◽  
pp. 52-57 ◽  
Author(s):  
K. M. MacLeod ◽  
J. H. McNeill
Keyword(s):  
Blood Vessels ◽  
Vascular Reactivity ◽  
Experimental Diabetes ◽  
Diabetic Rats ◽  
Cross Sectional Area ◽  
Consistent Pattern ◽  
Sectional Area ◽  
Cross Sectional ◽  
Onset Of Diabetes ◽  
Portal Veins

The influence of experimental diabetes induced by streptozotocin on responses of rat isolated aortae and portal veins to noradrenaline, 5-hydroxytryptamine, and KCl was examined 7, 100, 180, and 360 days after the onset of diabetes. No significant changes in reactivity were seen 7 days after the onset of diabetes. After 100 days aortae from diabetic rats were supersensitive (defined as a significant increase in the pD2 value) to noradrenaline. However, 180 days after the onset of diabetes, the sensitivity of diabetic aortae to noradrenaline was not significantly different from control, while the responsiveness (defined as the maximum developed tension ÷ cross-sectional area of aorta) to 5-hydroxytryptamine was reduced. A generalized increase in both the sensitivity and responsiveness of diabetic aortae to all three agonists was observed after 360 days of diabetes. In contrast, no changes in either the sensitivity or the responsiveness of portal veins to noradrenaline, 5-hydroxytryptamine, or KCl could be detected at any time after the onset of diabetes. These results indicate that changes in vascular reactivity can be detected with increasing duration of experimental diabetes. However, these changes do not follow a consistent pattern and are not seen in all parts of the vasculature.

Soluble and particulate phenylethanolamine N-methyltransferase in hypothalamus of diabetic rats

1992 ◽  
Vol 263 (2) ◽  
pp. E335-E339
Author(s):  
J. E. Chappell ◽  
J. K. Stewart
Keyword(s):  
Experimental Diabetes ◽  
Diabetic Rats ◽  
Particulate Fraction ◽  
Sprague Dawley ◽  
Rat Hypothalamus ◽  
Tissue Extracts ◽  
Sprague Dawley Rats ◽  
In Vitro Response

Experimental diabetes increases total phenylethanolamine N-methyltransferase (PNMT) activity in the medulla-pons but not in the hypothalamus. In this study diabetes was induced with streptozotocin (65 mg/kg) in male Sprague-Dawley rats. Twenty-eight days after treatment there were no differences in soluble PNMT activity in the hypothalamus of diabetics and controls, but PNMT activity in a membrane-associated (particulate) fraction of hypothalamus was evaluated approximately twofold in tissues of diabetic animals compared with controls. A specific PNMT inhibitor, incubated with tissue extracts of control rats, abolished greater than 90% of particulate PNMT activity in the hypothalamus but reduced soluble PNMT activity in the hypothalamus by only 47%. These findings indicate that membrane-associated PNMT activity in rat hypothalamus differs from soluble hypothalamic PNMT in the in vitro response to an inhibitor and the in vivo response to diabetes and suggest the importance of separating subcellular hypothalamic fractions prior to assay of PNMT.

scholarly journals Effect of alloxan-diabetes and treatment with anti-insulin serum on pathways of glucose metabolism in lactating rat mammary gland

1968 ◽  
Vol 109 (3) ◽  
pp. 407-417 ◽  
Author(s):  
Eileen Walters ◽  
Patricia McLean
Keyword(s):  
Mammary Gland ◽  
Glucose Oxidation ◽  
Alloxan Diabetes ◽  
Diabetic Rats ◽  
Control Group ◽  
Tissue Slices ◽  
Phosphogluconate Dehydrogenase ◽  
A Value ◽  
Glucose 6 Phosphate Dehydrogenase

1. The overall metabolic changes in lactating mammary gland in alloxan-diabetic and anti-insulin-serum-treated rats were assessed by measurement of the incorporation of 14C from specifically labelled glucose, pyruvate and acetate into carbon dioxide and lipid, together with measurements of enzymes concerned with the pentose phosphate pathway and with citrate metabolism. 2. Alloxan-diabetes depressed the rate of formation of 14CO2 from [1−14C]glucose and [2−14C]glucose to approx. 10% of the control rate; this was partially reversed by addition of insulin in vitro. The quotient Oxidation of [1−14C]glucose/Oxidation of [6−14C]glucose fell from a value of 17·6 in the control group to 3·9 in the diabetic group and was restored to 14·3 in the presence of insulin in vitro. In keeping with these results it was shown that glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities were significantly decreased in alloxan-diabetic rats. 3. Alloxan-diabetes depressed the decarboxylation and the oxidation of labelled pyruvate, but not the oxidation of labelled acetate. 4. The synthesis of lipid from specifically labelled glucose was greatly decreased, that from [2−14C]pyruvate was almost unchanged and that from [1−14C]acetate alone was increased in alloxandiabetic rats. However, the stimulation of lipid synthesis from acetate by glucose was small in the alloxan-diabetic rats compared with the controls. Insulin in vitro partially reversed all these effects. Both citrate-cleavage enzyme and acetate thiokinase activities were decreased in alloxan-diabetic rats. 5. Treatment of rats with anti-insulin serum depressed the formation of 14CO2 from [1−14C]glucose and [2−14C]glucose, but increased that from [6−14C]glucose. This was completely restored by the presence of insulin in vitro. The quotient Oxidation of [1−14C]glucose/Oxidation of [6−14C]glucose fell from a value of 17·6 in the control group to 3·8 in the anti-insulin-serum-treated group. There were no changes in the activity of glucose 6-phosphate dehydrogenase or 6-phosphogluconate dehydrogenase, but the hexokinase distribution changed and the content of the soluble fraction increased significantly. 6. The synthesis of lipid from specifically labelled glucose was depressed in anti-insulin-serum-treated rats; this effect was completely reversed by addition of insulin in vitro to the tissue slices.

Abnormal D cell secretion in alloxan-diabetes: influence by drug and aberrant metabolism

1984 ◽  
Vol 246 (6) ◽  
pp. E483-E492 ◽  
Author(s):  
V. Grill ◽  
S. Efendic
Keyword(s):  
Alloxan Diabetes ◽  
Cell Damage ◽  
Diabetic Rats ◽  
Cell Secretion ◽  
Isolated Perfused Pancreas ◽  
Metabolic Derangement ◽  
D Cell ◽  
Time Courses ◽  
D Cells

Abnormalities of somatostatin secretion in diabetes may be secondary to B cell damage with resulting insulinopenia or other effects of diabetogenic agents, including toxicity toward the somatostatin-producing D cells. These possibilities were evaluated in isolated perfused pancreas from normal and alloxan-diabetic rats. In normal rats 3-isobutyl-1-methylxanthine (IBMX, 1 mM), alpha-ketoisocaproic acid (KIC, 5 mM), D-glucose (27 mM), and D-glyceraldehyde (5 mM) stimulated somatostatin release. In diabetic rats 3 days after alloxan, IBMX and KIC elicited somatostatin release, whereas glucose or glyceraldehyde were without effect. In diabetic rats 14 days after alloxan, an otherwise (in normal and 3-day diabetic rats) nonstimulatory concentration of IBMX (0.05 mM) markedly stimulated somatostatin release, whereas as in 3-day diabetic rats glucose was ineffective. Insulin treatment for 2 days did not affect the somatostatin response to glucose in normal rats, did not restore a somatostatin response to glucose 3 days after alloxan, but partially restored (P less than 0.01) a response to glucose (28% of normal) 14 days after alloxan. Insulin in vitro (1 mU/ml, 20 min) failed to restore a glucose effect. Administration of alloxan (1.0 mM) for 5 min to pancreases from normal rats inhibited glucose-induced somatostatin response from 1,562 +/- 401 to 206 +/- 83 pg/15 min (P less than 0.01), whereas the response to IBMX (1 mM) was not significantly decreased. Following different time courses, both an effect of alloxan and of metabolic derangement inhibit somatostatin responses to glucose in alloxan diabetes.

scholarly journals The Influence of Indomethacin and Guanethidine on Experimental Streptozotocin Diabetic Neuropathy

1992 ◽  
Vol 19 (4) ◽  
pp. 433-441 ◽  
Author(s):  
Douglas W. Zochodne ◽  
Lam T. Ho
Keyword(s):  
Diabetic Neuropathy ◽  
Oxygen Tension ◽  
Experimental Diabetes ◽  
Diabetic Rats ◽  
Sensory Conduction ◽  
Oxygen Tensions ◽  
Combined Strategy ◽  
Microvascular Resistance

ABSTRACT:In diabetic animals, reduced endoneurial perfusion and oxygen content have been linked to neuropathic abnormalities and might be amenable to pharmacological manipulation. In streptozotocin-induced diabetic rats, we studied the influence of guanethidine adrenergic sympathectomy, indomethacin treatment and a combined strategy on: serial in vivo motor and sensory conduction, resistance to ischemic conduction failure, in vitro myelinated and unmyelinated conduction, endoneurial perfusion and endoneurial oxygen tension. Unlike previous work diabetic animals had normal endoneurial perfusion but lower endoneurial oxygen tensions after six months of hyperglycemia. Guanethidine worsened sensory conduction despite lower microvascular resistance and an improvement in endoneurial oxygen tension. In contrast, indomethacin improved motor and sensory conduction but not oxygen tension. These studies do not support a linkage between conduction deficits and early endoneurial microangiopathy in experimental diabetes. Indomethacin, or related agents may offer a new therapeutic approach toward diabetic neuropathy through a mechanism independent of the endoneurial microvasculature.

EFFECT OF INSULIN AND ADRENALINE ON CYCLIC AMP IN THE DIAPHRAGM OF NORMAL AND DIABETIC RATS

1977 ◽  
Vol 85 (4) ◽  
pp. 806-817 ◽  
Author(s):  
Staffan Edén ◽  
Kerstin Albertsson-Wikland ◽  
Sten Rosberg ◽  
Olle Isaksson
Keyword(s):  
Skeletal Muscle ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Enzyme Activities ◽  
Experimental Diabetes ◽  
Diabetic Rats ◽  
Camp Levels ◽  
Adrenaline Injection

ABSTRACT The effects of insulin and adrenaline on cyclic AMP (cAMP) levels in diaphragms of normal, streptozotocin-diabetic and insulin-treated diabetic rats were studied. Adrenaline caused a biphasic rise in cAMP with peak values of cAMP within the first few minutes. Diaphragms of diabetic rats showed an increased responsiveness to adrenaline. Injection of insulin to diabetic rats normalized the rise in cAMP after addition of adrenaline. There was no difference in basal levels of cAMP between diaphragms of normal, diabetic or insulin-treated diabetic rats. Insulin in vitro did not affect basal cAMP-levels or the release of cAMP from the tissue but significantly decreased adrenaline-induced peak levels of cAMP. This effect of insulin was abolished by theophylline. The results of the present study suggest that experimental diabetes is associated with changes of the adenylate cyclase and/or phosphodiesterase enzyme activities in skeletal muscle resulting in an increased responsiveness to adrenaline. Since insulin in vitro depressed the adrenaline-induced elevation of cAMP the increased responsiveness in diaphragms of diabetic rats might be attributed to the specific lack of insulin.

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