Glycemia-lowering effect of cobalt chloride in the diabetic rat: role of decreased gluconeogenesis

1998 ◽  
Vol 274 (6) ◽  
pp. E984-E991 ◽  
Author(s):  
Firas Saker ◽  
Juan Ybarra ◽  
Patrick Leahy ◽  
Richard W. Hanson ◽  
Satish C. Kalhan ◽  
...  
Keyword(s):  
Cobalt Chloride ◽  
Glucose Production ◽  
Serum Glucose ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Mrna Levels ◽  
Lowering Effect ◽  
Significant Decrement ◽  
Camp Levels

Results of previous studies indicated that treatment of diabetic rats (induced by streptozotocin) with cobalt chloride (CoCl2) resulted in a significant decrement in serum glucose concentration. The present study was designed to determine the potential role of enhanced glucose uptake vs. decreased glucose production in the above response. The rate of systemic appearance of glucose, measured under fasting conditions using [3-3H]glucose tracer, was reduced from 35.5 ± 2.5 to 17.5 ± 1.8 μmol ⋅ kg−1 ⋅ min−1in diabetic rats treated with 2 mM CoCl2 added to the drinking water for 10–14 days ( P < 0.01). Tissue accumulation of intravenously administered 2-deoxy-[14C]glucose was significantly reduced in kidney and eye of diabetic rats treated with CoCl2, whereas the uptake remained unchanged in several other tissues including cerebrum, red and white skeletal muscle, heart, and liver. The relative content of phospho enolpyruvate carboxykinase (PEPCK) mRNA was increased 3.1-fold in livers of diabetic compared with normal rats ( P < 0.001), and treatment of diabetic rats with CoCl2 decreased hepatic PEPCK mRNA levels to normal. The content of PEPCK mRNA in the liver was decreased by 33% in CoCl2-treated normal rats ( P < 0.05). Treatment with CoCl2 resulted in no change in cAMP levels in the livers of either diabetic or normal rats. These results suggest that the glycemia-lowering effect of CoCl2 is mediated by reductions in the rate of systemic appearance of glucose and hepatic gluconeogenesis.

scholarly journals Microarray analysis reveals novel gene expression changes associated with erectile dysfunction in diabetic rats

2005 ◽  
Vol 23 (2) ◽  
pp. 192-205 ◽  
Author(s):  
Chris J. Sullivan ◽  
Thomas H. Teal ◽  
Ian P. Luttrell ◽  
Khoa B. Tran ◽  
Mette A. Peters ◽  
...  
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Erectile Dysfunction ◽  
Splice Variants ◽  
Full Range ◽  
Diabetic Rats ◽  
Differentially Expressed ◽  
Diabetic Rat ◽  
Literature Mining ◽  
Mrna Levels

To investigate the full range of molecular changes associated with erectile dysfunction (ED) in Type 1 diabetes, we examined alterations in penile gene expression in streptozotocin-induced diabetic rats and littermate controls. With the use of Affymetrix GeneChip arrays and statistical filtering, 529 genes/transcripts were considered to be differentially expressed in the diabetic rat cavernosum compared with control. Gene Ontology (GO) classification indicated that there was a decrease in numerous extracellular matrix genes (e.g., collagen and elastin related) and an increase in oxidative stress-associated genes in the diabetic rat cavernosum. In addition, PubMatrix literature mining identified differentially expressed genes previously shown to mediate vascular dysfunction [e.g., ceruloplasmin ( Cp), lipoprotein lipase, and Cd36] as well as genes involved in the modulation of the smooth muscle phenotype (e.g., Kruppel-like factor 5 and chemokine C-X3-C motif ligand 1). Real-time PCR was used to confirm changes in expression for 23 relevant genes. Further validation of Cp expression in the diabetic rat cavernosum demonstrated increased mRNA levels of the secreted and anchored splice variants of Cp. CP protein levels showed a 1.9-fold increase in tissues from diabetic rats versus controls. Immunohistochemistry demonstrated localization of CP protein in cavernosal sinusoids of control and diabetic animals, including endothelial and smooth muscle layers. Overall, this study broadens the scope of candidate genes and pathways that may be relevant to the pathophysiology of diabetes-induced ED as well as highlights the potential complexity of this disorder.

scholarly journals Hypoglycaemic Property of Nutraceuticals

1970 ◽  
Vol 6 (2) ◽  
pp. 105-107
Author(s):  
Mohammad Emdadul Haque ◽  
Quazi Safayetullah ◽  
Monira Ahsan ◽  
Sheikh Nazrul Islam
Keyword(s):  
Glucose Level ◽  
Day Treatment ◽  
Positive Control ◽  
Serum Glucose ◽  
Negative Control ◽  
Diabetic Rats ◽  
Serum Glucose Level ◽  
Diabetic Rat ◽  
Black Cumin ◽  
Control Serum

Hypoglycemic property of four nutraceuticals named - black cumin, garlic, methi and karela has been investigated on an alloxan induced diabetic rat model. Glibenclamide was used as positive control and normal saline was used as negative control. Serum glucose levels of normal and diabetic induced rats were estimated by Glucose Oxidase method using a kit, and it were 4.33 ± 0.43 mmol/L and 8.27 ± 0.45mmol/L respectively. The alloxan induced diabetic rats were grouped into six, which were then treated with the four nutraceuticals and two controls. Treatment was given orally everyday for 28 days. Serum glucose level was analysed every 7 day intervals. It was observed that lowering of glucose level was significant (P = 0.01) for every 7 day treatment period. All of the nutraceuticals reduced the serum glucose level nearly to the normal value within 28 days. The rate of lowering of the glucose level was found to vary with the nutraceuticals. Garlic was found to be most active like the glibenclamide. The next active one was black cumin followed by methi and karela. The study conclude that nutraceuticals possess significant hypoglycemic property. Key words: Hypoglycaemia; Nutraceuticals; Black cumin; Garlic; Methi; Karela. Dhaka Univ. J. Pharm. Sci. 6(2): 105-107, 2007 (December)

Effect of experimental diabetes on rat cardiac cAMP, phosphorylase, and inotropy

1983 ◽  
Vol 244 (6) ◽  
pp. H844-H851 ◽  
Author(s):  
R. V. Vadlamudi ◽  
J. H. McNeill
Keyword(s):  
Experimental Diabetes ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Phosphorylase Activity ◽  
Camp Content ◽  
Rat Hearts ◽  
Underlying Causes ◽  
Camp Levels ◽  
Working Rat Heart ◽  
Time Point

The isolated perfused working rat heart was used to study experimental diabetes-induced alterations in the effect of isoproterenol on adenosine 3',5'-cyclic monophosphate (cAMP) content, inotropy, and phosphorylase activity. Experimental diabetes was induced by intravenous injection of either alloxan (40 mg/kg) or streptozotocin (50 mg/kg). There were no changes in either basal cAMP levels or in isoproterenol-induced cAMP levels in hearts from diabetic rats at either 3 days or 100-120 days after induction of diabetes. Maximum changes produced by isoproterenol in positive and negative dP/dt developments of diabetic rat hearts were also not different from control at either time point. However, phosphorylase was activated to a significantly greater extent by isoproterenol in hearts obtained from acute as well as chronic diabetic rats. Chronic diabetic rat hearts exhibited significantly higher total phosphorylase activity. Diabetic rat hearts had slightly but not significantly higher basal phosphorylase a activity. Furthermore, prostaglandin E1 activated phosphorylase in diabetic rat hearts but not in control rat hearts. Acute metabolic derangements and alterations in Ca2+ homeostasis caused by diabetes could be the underlying causes for this phosphorylase response. Thyroid hormone levels were depressed in diabetic rats. However, hypothyroidism is probably not responsible for the alterations in phosphorylase activity.

Sexual dysfunction in the diabetic BB/WOR rat: a role of central neuropathy

1997 ◽  
Vol 272 (1) ◽  
pp. R259-R267 ◽  
Author(s):  
K. T. McVary ◽  
C. H. Rathnau ◽  
K. E. McKenna
Keyword(s):  
Sexual Function ◽  
Diabetic Rats ◽  
Nerve Fibers ◽  
Diabetic Rat ◽  
Penile Erections ◽  
Reflex Testing ◽  
Diabetic Impotence ◽  
Central Neuropathy ◽  
Sexual Reflexes

The pathophysiological mechanisms of diabetic impotence remain obscure. We have presented an analysis of sexual function in a diabetic rat (BB/WOR) model characterized by diffuse neuropathic changes without a confounding vasculopathy that allows us to define the neural components of erectile failure. Copulatory behavioral testing demonstrated that diabetic males were severely impaired: the controls mounted three times more than the diabetics and had about one-half the latency to first mount. The diabetics had about one-fourth the number of intromissions and took nearly twice as long to achieve first ejaculation. The number of ejaculations was drastically reduced as well. We examined sexual reflexes in the anesthetized acutely spinalized rat. These experiments tested the integrity of spinal circuits controlling sexual function. Reflex testing demonstrated that spinal sexual reflexes were also severely impaired: the onset latency of reflexes was more than doubled, and the duration of reflexes was less than one-half. More than one-half of the diabetic rats showed no penile erections. Neural studies showed even more derangement in reflex measures in rats, without erection. Nerve conduction velocity experiments suggested a peripheral neuropathic change in hypogastric nerve and motor pudendal nerve fibers. These dysfunctional findings were seen without any androgen deficiency. These results indicate that diabetic impotence in this model reflects central and peripheral neuropathic disease processes.

Studies on regulatory mechanisms of heme biosynthesis in hepatocytes from normal and experimental-diabetic rats. Role of insulin

1990 ◽  
Vol 68 (6) ◽  
pp. 914-921 ◽  
Author(s):  
Eduardo T. Cánepa ◽  
Elena B. C. Llambías ◽  
Moisés Grinstein
Keyword(s):  
Aminolevulinic Acid ◽  
Rat Hepatocytes ◽  
Isolated Hepatocytes ◽  
Inhibitory Effect ◽  
Diabetic Rats ◽  
Significant Inhibition ◽  
Diabetic Rat ◽  
Experimental Conditions ◽  
Cytochrome P 450

In the present work we demonstrate that insulin decreases the phenobarbital-induced activities of δ-aminolevulinic acid synthase and ferrochelatase in isolated hepatocytes from normal and experimental-diabetic rats. Insulin concentrations required to produce significant inhibition in diabetic hepatocytes were higher than in normal cells. Under similar experimental conditions, insulin decreased the basal activities of δ-aminolevulinic acid synthase and ferrochelatase in hepatocytes from normal rats; no inhibitory effect was observed on the basal activity of δ-aminolevulinic acid synthase in hepatocytes from diabetic rats. Cytochrome P-450 content of both normal and diabetic cells was not affected by insulin in absence or presence of phenobarbital. The inhibitory action of insulin was exerted even when effective concentrations of glucagon, dexamethasone, or 8-(p-chlorophenylthio)-cAMP were present.Key words: δ-aminolevulinic acid synthase, ferrochelatase, cAMP, insulin, diabetic rat hepatocytes.

Differential accumulation of insulin-like growth factor-I in kidneys of pre- and postpubertal streptozotocin-diabetic rats

1994 ◽  
Vol 12 (2) ◽  
pp. 215-224 ◽  
Author(s):  
M Phillip ◽  
H Werner ◽  
T Palese ◽  
A A Kowarski ◽  
B Stannard ◽  
...  
Keyword(s):  
Young Patients ◽  
Experimental Models ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Mrna Levels ◽  
Kidney Size ◽  
Local Synthesis ◽  
Receptor Mrna ◽  
Igf I ◽  
Renal Changes

ABSTRACT Nephropathy, one of the major complications of diabetes mellitus, is characterized by an early increase in kidney size. In experimental models of diabetes, this event is preceded by a rapid and transient rise in kidney IGF-I levels, at least in adult animals. Since diabetes-associated renal changes are uncommon in young patients, we investigated the early changes in the components of the IGF system following induction of diabetes in prepubertal and postpubertal rats. The rationale for this study was the evaluation of potential differences which could lead to kidney complications only at adult stages. Unlike the situation in the postpubertal kidney, in which there was a transient accumulation of extractable IGF-I 24–48 h after streptozotocin (STZ) administration, there was a decrease of ∼12-fold in the level of IGF-I in the prepubertal kidney over the same period of time. Paradoxically, kidney IGF-I mRNA levels were reduced by ∼50% in the postpubertal rat 24 h after STZ treatment, whereas in the prepubertal kidney IGF-I mRNA levels were unaltered. Furthermore, the levels of IGF-I receptor mRNA and 125I-labelled IGF-I binding to kidney membranes of postpubertal diabetic rats were similar to the levels in control kidneys. On the other hand, both the levels of IGF-I receptor mRNA and 125I-labelled IGF-I binding were increased (∼2·5-fold (after 24 h) and ∼ 3-fold (after 48 h) respectively) in prepubertal animals. In addition, increased expression of IGF-binding protein (IGFBP)-1 mRNA was seen early in diabetes in both pre- and postpubertal rats. The results of this study suggest that the transient accumulation of IGF-I in the kidney of the postpubertal diabetic rat may not be due to an increase in the local synthesis of IGF-I, but rather to an increase in IGF-I uptake from the circulation due to non-membrane-associated IGFBP-1. The lack of accumulation of IGF-I in the prepubertal kidney probably reflects the ∼ 10-fold lower levels of circulating IGF-I in young as compared with adult diabetic rats.

Reduced conduction reserve in the diabetic rat heart: role of iPLA2 activation in the response to ischemia

2011 ◽  
Vol 300 (1) ◽  
pp. H326-H334 ◽  
Author(s):  
Parisa Rahnema ◽  
Yakhin Shimoni ◽  
Anders Nygren
Keyword(s):  
Conduction Velocity ◽  
Electrical Coupling ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Acute Ischemia ◽  
Cellular Excitability ◽  
Bromoenol Lactone ◽  
Healthy Control ◽  
Time To Onset

Hearts from streptozotocin (STZ)-induced diabetic rats have previously been shown to have impaired intercellular electrical coupling, due to reorganization (lateralization) of connexin43 proteins. Due to the resulting reduction in conduction reserve, conduction velocity in diabetic hearts is more sensitive to conditions that reduce cellular excitability or intercellular electrical coupling. Diabetes is a known risk factor for cardiac ischemia, a condition associated with both reduced cellular excitability and reduced intercellular coupling. Activation of Ca2+-independent phospholipase A2 (iPLA2) is known to be part of the response to acute ischemia and may contribute to the intercellular uncoupling by causing increased levels of arachidonic acid and lysophosphatidyl choline. Normally perfused diabetic hearts are known to exhibit increased iPLA2 activity and may thus be particularly sensitive to further activation of these enzymes. In this study, we used voltage-sensitive dye mapping to assess changes in conduction velocity in response to acute global ischemia in Langendorff-perfused STZ-induced diabetic hearts. Conduction slowing in response to ischemia was significantly larger in STZ-induced diabetic hearts compared with healthy controls. Similarly, slowing of conduction velocity in response to acidosis was also more pronounced in STZ-induced diabetic hearts. Inhibition of iPLA2 activity using bromoenol lactone (BEL; 10 μM) had no effect on the response to ischemia in healthy control hearts. However, in STZ-induced diabetic hearts, BEL significantly reduced the amount of conduction slowing observed beginning 5 min after the onset of ischemia. BEL treatment also significantly increased the time to onset of sustained arrhythmias in STZ-induced diabetic hearts but had no effect on the time to arrhythmia in healthy control hearts. Thus, our results suggest that iPLA2 activation in response to acute ischemia in STZ-induced diabetic hearts is more pronounced than in control hearts and that this response is a significant contributor to arrhythmogenic conduction slowing.

Effects of vanadium treatment on the alterations of cardiac glycogen phosphorylase and phosphorylase kinase in streptozotocin-induced chronic diabetic rats

1994 ◽  
Vol 72 (12) ◽  
pp. 1537-1543 ◽  
Author(s):  
Heyi Liu ◽  
John H. McNeill
Keyword(s):  
Rat Heart ◽  
Diabetic Rats ◽  
Diabetic Heart ◽  
Diabetic Rat ◽  
Phosphorylase Kinase ◽  
Beneficial Effects ◽  
Camp Pathway ◽  
Vanadyl Sulphate ◽  
Camp Levels ◽  
Camp Elevation

Supersensitivity to isoproterenol (ISO) induced activation of cardiac phosphorylase in diabetic rat heart has been previously demonstrated and was also reproduced in this study. To explore further the nature of this supersensitivity, we examined the activity of phosphorylase kinase and the level of cyclic AMP (cAMP) in this tissue. We observed a significantly enhanced activation of phosphorylase kinase but no increase in cAMP levels in response to ISO stimulation in diabetic rat heart, suggesting that the supersensitivity of phosphorylase activation in diabetic heart may result from an enhanced activation of phosphorylase kinase that does not involve the cAMP pathway. On the other hand, perfusion of diabetic rat heart with verapamil (5 × 10−8 M) prior to ISO stimulation abolished the enhanced cardiac phosphorylase activation, suggesting a role for calcium in the supersensitivity of phosphorylase activation. Furthermore, treatment of the diabetic rats with an insulin-like compound, vanadyl sulphate, completely abolished the enhanced cardiac phosphorylase activation and restored the increase in ISO-induced cAMP elevation in diabetic heart. The present study has provided further information on the changes of phosphorylase activation in the diabetic rat heart and demonstrated beneficial effects of vanadyl sulphate on the pathway leading to phosphorylase activation in diabetic rat heart.Key words: phosphorylase, phosphorylase kinase, catecholamines, vanadium.

Acute insulin withdrawal contributes to ischemic heart failure in spontaneously diabetic BB Wistar rats

1990 ◽  
Vol 68 (3) ◽  
pp. 462-466 ◽  
Author(s):  
Gary D. Lopaschuk ◽  
Marguerite A. Spafford
Keyword(s):  
Fatty Acids ◽  
Metabolic Control ◽  
Wistar Rats ◽  
Insulin Treatment ◽  
Serum Glucose ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Metabolic Demand ◽  
Significant Deterioration ◽  
Direct Demonstration

The contribution of poor metabolic control to myocardial ischemic failure was determined in isolated working hearts from insulin-dependent BB Wistar rats. Removal of insulin treatment 24 h prior to study (uncontrolled diabetic rats) resulted in significant increases in serum glucose, serum fatty acids, and myocardial triglyceride, compared with animals in which insulin treatment was not withheld (insulin-treated diabetic rats). Isolated working hearts obtained from these two groups were subjected to a 40% reduction in coronary flow in the presence of a maintained metabolic demand (hearts were paced at 200 beats/min and perfused at an 80 mmHg (1 mmHg = 133.3 Pa) left aortic afterload, 11.5 mmHg left atrial preload). Within 15 min of ischemia, a significant deterioration of mechanical function occurred in the uncontrolled diabetic rats, whereas function was maintained in the insulin-treated diabetic rats. Oxygen consumption by the two groups of hearts was similar prior to the onset of ischemia and decreased during ischemia in parallel with the work performed by the hearts. This suggests that the accelerated failure rate in uncontrolled diabetic rat hearts is unlikely a result of an increased oxygen requirement. These data are a direct demonstration that acute changes in metabolic control of the diabetic can contribute to the severity of myocardial ischemic injury.Key words: diabetes, heart, ischemia, fatty acids.

scholarly journals Diabetes Attenuates the Contribution of Endogenous Nitric Oxide but Not Nitroxyl to Endothelium Dependent Relaxation of Rat Carotid Arteries

2021 ◽  
Vol 11 ◽  
Author(s):  
Jasmin Chendi Li ◽  
Anida Velagic ◽  
Cheng Xue Qin ◽  
Mandy Li ◽  
Chen Huei Leo ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Nitrogen Oxide ◽  
Carotid Arteries ◽  
Body Weight Gain ◽  
Vascular Complications ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Endothelium Dependent Relaxation

Introduction:Endothelial dysfunction is a major risk factor for several of the vascular complications of diabetes, including ischemic stroke. Nitroxyl (HNO), the one electron reduced and protonated form of nitric oxide (NO•), is resistant to scavenging by superoxide, but the role of HNO in diabetes mellitus associated endothelial dysfunction in the carotid artery remains unknown.Aim: To assess how diabetes affects the role of endogenous NO• and HNO in endothelium-dependent relaxation in rat isolated carotid arteries.Methods: Male Sprague Dawley rats were fed a high-fat-diet (HFD) for 2 weeks prior to administration of low dose streptozotocin (STZ; 35 mg/kg i. p./day) for 2 days. The HFD was continued for a further 12 weeks. Sham rats were fed standard chow and administered with citrate vehicle. After 14 weeks total, rats were anesthetized and carotid arteries collected to assess responses to the endothelium-dependent vasodilator, acetylcholine (ACh) by myography. The combination of calcium-activated potassium channel blockers, TRAM-34 (1 μmol/L) and apamin (1 μmol/L) was used to assess the contribution of endothelium-dependent hyperpolarization to relaxation. The corresponding contribution of NOS-derived nitrogen oxide species to relaxation was assessed using the combination of the NO• synthase inhibitor, L-NAME (200 μmol/L) and the soluble guanylate cyclase inhibitor ODQ (10 μmol/L). Lastly, L-cysteine (3 mmol/L), a selective HNO scavenger, and hydroxocobalamin (HXC; 100 μmol/L), a NO• scavenger, were used to distinguish between NO• and HNO-mediated relaxation.Results: At study end, diabetic rats exhibited significantly retarded body weight gain and elevated blood glucose levels compared to sham rats. The sensitivity and the maximal relaxation response to ACh was significantly impaired in carotid arteries from diabetic rats, indicating endothelial dysfunction. The vasorelaxation evoked by ACh was abolished by L-NAME plus ODQ, but not affected by the apamin plus TRAM-34 combination, indicating that NOS-derived nitrogen oxide species are the predominant endothelium-derived vasodilators in sham and diabetic rat carotid arteries. The maximum relaxation to ACh was significantly decreased by L-cysteine in both sham and diabetic rats, whereas HXC attenuated ACh-induced relaxation only in sham rats, suggesting that diabetes impaired the contribution of NO•, whereas HNO-mediated vasorelaxation remained intact.Conclusion: Both NO• and HNO contribute to endothelium-dependent relaxation in carotid arteries. In diabetes, NO•-mediated relaxation is impaired, whereas HNO-mediated relaxation was preserved. The potential for preserved HNO activity under pathological conditions that are associated with oxidative stress indicates that HNO donors may represent a viable therapeutic approach to the treatment of vascular dysfunction.

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