Metabolism of VLDL is increased in streptozotocin-induced diabetic rat hearts

2000 ◽  
Vol 278 (6) ◽  
pp. H1874-H1882 ◽  
Author(s):  
Nandakumar Sambandam ◽  
Mohammed A. Abrahani ◽  
Scott Craig ◽  
Osama Al-Atar ◽  
Esther Jeon ◽  
...  
Keyword(s):  
Lipolytic Activity ◽  
Isolated Heart ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Diabetic Rats ◽  
Diabetic Heart ◽  
Diabetic Rat ◽  
Rat Hearts ◽  
Heparin Plasma

In streptozotocin (STZ)-induced diabetic rats, we previously showed an increased heparin-releasable (luminal) lipoprotein lipase (LPL) activity from perfused hearts. To study the effect of this enlarged LPL pool on triglyceride (TG)-rich lipoproteins, we examined the metabolism of very-low-density lipoprotein (VLDL) perfused through control and diabetic hearts. Diabetic rats had elevated TG levels compared with control. However, fasting for 16 h abolished this difference. When the plasma lipoprotein fraction of density <1.006 g/ml from fasted control and diabetic rats was incubated in vitro with purified bovine or rat LPL, VLDL from diabetic animals was hydrolyzed as proficiently as VLDL from control animals. Post-heparin plasma lipolytic activity was comparable in control and diabetic animals. However, perfusion of control and diabetic rats with heparinase indicated that diabetic hearts had larger amounts of LPL bound to heparan sulfate proteoglycan-binding sites. [3H]VLDL obtained from control rats, when recirculated through the isolated heart, disappeared at a significantly faster rate from diabetic than from control rat hearts. This increased VLDL-TG hydrolysis was essentially abolished by prior perfusion of the diabetic heart with heparin, implicating LPL in this process. These findings suggest that the enlarged LPL pool in the diabetic heart is present at a functionally relevant location (at the capillary lumen) and is capable of hydrolyzing VLDL. This could increase the delivery of free fatty acid to the heart, and the resultant metabolic changes could induce the subsequent cardiomyopathy that is observed in the chronic diabetic rat.

Metabolism of very-low-density lipoprotein and chylomicrons by streptozotocin-induced diabetic rat heart: effects of diabetes and lipoprotein preference

2008 ◽  
Vol 295 (5) ◽  
pp. E1106-E1116 ◽  
Author(s):  
You-Guo Niu ◽  
Rhys D. Evans
Keyword(s):  
Glucose Oxidation ◽  
Early Stage ◽  
Low Density Lipoprotein ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
And Control

Very-low-density lipoprotein (VLDL) and chylomicrons (CM) are major sources of fatty acid supply to the heart, but little is known about their metabolism in diabetic myocardium. To investigate this, working hearts isolated from control rats and diabetic rats 2 wk following streptozotocin (STZ) injection were perfused with control and diabetic lipoproteins. Analysis of the diabetic lipoproteins showed that both VLDL and CM were altered compared with control lipoproteins; both were smaller and had different apolipoprotein composition. Heparin-releasable lipoprotein lipase (HR-LPL) activity was increased in STZ-induced diabetic hearts, but tissue residual LPL activity was decreased; moreover, diabetic lipoproteins stimulated HR-LPL activity in both diabetic and control hearts. Diabetic hearts oxidized lipoprotein-triacylglycerol (TAG) to a significantly greater extent than controls (>80% compared with deposition as tissue lipid), and the oxidation rate of exogenous lipoprotein-TAG was increased significantly in diabetic hearts regardless of TAG source. Significantly increased intracardiomyocyte TAG accumulation was found in diabetic hearts, although cardiac mechanical function was not inhibited, suggesting that lipotoxicity precedes impaired cardiac performance. Glucose oxidation was significantly decreased in diabetic hearts; additionally, however, diabetic lipoproteins decreased glucose oxidation in diabetic and control hearts. These results demonstrate increased TAG-rich lipoprotein metabolism concomitant with decreased glucose oxidation in type 1 diabetic hearts, and the alterations in cardiac lipoprotein metabolism may be due to the properties of diabetic TAG-rich lipoproteins as well as the diabetic state of the myocardium. These changes were not related to cardiomyopathy at this early stage of diabetes.

Plasma Post-Heparin Lipolytic Activity in Patients with Malabsorption: Effect of Intravenous Fat Administration

1974 ◽  
Vol 46 (6) ◽  
pp. 743-751 ◽  
Author(s):  
M. Press ◽  
G. R. Thompson
Keyword(s):  
Lipolytic Activity ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Coconut Oil ◽  
Normal Subjects ◽  
Artificial Substrates ◽  
Oil Emulsion ◽  
Heparin Plasma ◽  
Post Heparin Lipolytic Activity ◽  
Therapeutic Doses

1. Post-heparin lipolytic activity was determined in the plasma of thirteen patients with malabsorption and fourteen healthy controls, with a coconut-oil emulsion (Ediol), triolein and very-low-density lipoprotein (VLDL) as substrates. 2. Significantly lower post-heparin lipolytic activities were found in malabsorbers, whichever substrate was used. Lipolysis was inhibited by 0–5 mol/l sodium chloride when VLDL was the substrate but not when the two artificial substrates were used. 3. Plasma post-heparin lipolytic activities rose in malabsorbers after therapeutic doses of an intravenous fat emulsion (Intralipid), especially when assayed against VLDL. 4. The abnormal fatty acid composition of VLDL from malabsorbers did not affect its properties as a substrate for lipolysis by post-heparin plasma from normal subjects. 5. These findings support the concept that PHLA is heterogeneous in origin. They also suggest that if reduced clearance is a factor in the hypertriglyceridaemia sometimes seen in malabsorption, it is due to an enzyme deficit rather than a substrate defect.

scholarly journals Restoration in vitro of normal rates of very-low-density lipoprotein triacylglycerol and apoprotein B secretion in hepatocyte cultures from diabetic rats

1993 ◽  
Vol 294 (1) ◽  
pp. 167-171 ◽  
Author(s):  
J M Duerden ◽  
G F Gibbons
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Basal Medium ◽  
Inhibitory Response ◽  
Diabetic Rats ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Culture Dish ◽  
Apoprotein B

Hepatocytes derived from diabetic rats were cultured in serum-free Waymouth's medium containing various supplements, after an initial 4 h period during which the cells were allowed to attach to the culture dish in the presence of foetal-bovine serum (10%). After removal of serum, these cells secreted much less very-low-density lipoprotein (VLDL) apoprotein B (apoB) and triacylglycerol than those derived from normal rats when cultured for 24 h in the basal medium. Inclusion of oleate (0.75 mM) in the medium initially increased the output of apoB and triacylglycerol, but the rates remained lower than those observed in normal hepatocytes and declined to zero after 72 h. This time-dependent decline in VLDL output was prevented by addition of dexamethasone to the oleate-containing medium. Levels of apoB and triacylglycerol output characteristic of normal hepatocytes could only be completely restored, however, by further addition of a mixture of lipogenic substrates (lactate plus pyruvate) to the medium. Restoration of normal levels of VLDL secretion in diabetic hepatocytes in vitro by this means was accompanied by a normal inhibitory response of apoB and triacylglycerol output to short-term (24 h) treatment with insulin or glucagon. Exposure of the cells to insulin for 72 h enhanced the secretion of VLDL, whereas treatment with glucagon for the same period potentiated the original inhibitory effect. The defective secretion of VLDL apoB observed when diabetic hepatocytes were cultured in the basal medium for 24 h could also be rectified by inclusion of a mixture of oleate (0.75 mM), lactate (10 mM), pyruvate (1 mM), dexamethasone (1 microM) and insulin (78 nM) in the medium during the 4 h attachment period in the presence of serum. Under these conditions, the increase in the secretory response of triacylglycerol was not so pronounced.

scholarly journals Sustained In Vitro and In Vivo Delivery of Metformin from Plant Pollen-Derived Composite Microcapsules

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1048
Author(s):  
Noha M. Meligi ◽  
Amro K.F. Dyab ◽  
Vesselin N. Paunov
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Phoenix Dactylifera ◽  
Relative Bioavailability ◽  
Diabetic Rats ◽  
In Vivo Studies ◽  
Pharmacokinetic Parameters ◽  
Sprague Dawley

We developed a dual microencapsulation platform for the type 2 diabetes drug metformin (MTF), which is aimed to increase its bioavailability. We report the use of Lycopodium clavatum sporopollenin (LCS), derived from their natural spores, and raw Phoenix dactylifera L. (date palm) pollens (DPP) for MTF microencapsulation. MTF was loaded into LCS and DPP via a vacuum and a novel method of hydration-induced swelling. The loading capacity (LC) and encapsulation efficiency (EE) percentages for MTF-loaded LCS and MTF-loaded DPP microcapsules were 14.9% ± 0.7, 29.8 ± 0.8, and 15.2% ± 0.7, 30.3 ± 1.0, respectively. The release of MTF from MTF-loaded LCS microcapsules was additionally controlled by re-encapsulating the loaded microcapsules into calcium alginate (ALG) microbeads via ionotropic gelation, where the release of MTF was found to be significantly slower and pH-dependent. The pharmacokinetic parameters, obtained from the in vivo study, revealed that the relative bioavailability of the MTF-loaded LCS-ALG beads was 1.215 times higher compared to pure MTF, following oral administration of a single dose equivalent to 25 mg/kg body weight MTF to streptozotocin (STZ)-induced diabetic male Sprague-Dawley rats. Significant hypoglycemic effect was obtained for STZ-induced diabetic rats orally treated with MTF-loaded LCS-ALG beads compared to control diabetic rats. Over a period of 29 days, the STZ-induced diabetic rats treated with MTF-loaded LCS-ALG beads showed a decrease in the aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglycerides, cholesterol, and low-density lipoprotein-cholesterol (LDL-C) levels, as well as an increase in glutathione peroxidase (GPx) and a recovery in the oxidative stress biomarker, lipid peroxidation (LPx). In addition, histopathological studies of liver, pancreas, kidney, and testes suggested that MTF-loaded LCS-ALG beads improved the degenerative changes in organs of diabetic rats. The LCS-ALG platform for dual encapsulation of MTF achieved sustained MTF delivery and enhancement of bioavailability, as well as the improved biochemical and histopathological characteristics in in vivo studies, opening many other intriguing applications in sustained drug delivery.

scholarly journals Isolated downregulation of HCN2 in ventricles of rats with streptozotocin-induced diabetic cardiomyopathy

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Katarina Hadova ◽  
Eva Kralova ◽  
Gabriel Doka ◽  
Lenka Bies Pivackova ◽  
Zuzana Kmecova ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Diabetic Rats ◽  
Diabetic Heart ◽  
H9c2 Cell ◽  
Hcn Channels ◽  
Compensatory Mechanism ◽  
Mrna Levels ◽  
Rat Hearts ◽  
Protein Expressions

Abstract Background In spite of disrupted repolarization of diabetic heart, some studies report less tendency of diabetic heart to develop ventricular arrhythmias suggesting effective compensatory mechanism. We hypothesized that myocardial alterations in HCN2 and HCN4 channels occur under hyperglycaemia. Methods Diabetes was induced in rats using a single injection of streptozotocin (STZ; 55 mg/kg body weight, i.p.). Basal ECG was measured. Expression of mRNA for HCN channels, potassium channels and microRNA 1 and 133a were measured in ventricular tissues. Protein expression of HCN2 channel isoform was assessed in five different regions of the heart by western blotting. Differentiated H9c2 cell line was used to examine HCN channels expression under hyperglycaemia in vitro. Results Six weeks after STZ administration, heart rate was reduced, QRS complex duration, QT interval and T-wave were prolonged in diabetic rats compared to controls. mRNA and protein expressions of HCN2 decreased exclusively in the ventricles of diabetic rats. HCN2 expression levels in atria of STZ rats and H9c2 cells treated with excess of glucose were not changed. MicroRNA levels were stable in STZ rat hearts. We found significantly decreased mRNA levels of several potassium channels participating in repolarization, namely Kcnd2 (Ito1), Kcnh2 (IKr), Kcnq1 (IKs) and Kcnj11 (IKATP). Conclusions This result together with downregulated HCN2 channels suggest that HCN channels might be an integral part of ventricular electric remodelling and might play a role in cardiac repolarization projected in altered arrhythmogenic profile of diabetic heart.

Metformin improves cardiac function in isolated streptozotocin-diabetic rat hearts

1994 ◽  
Vol 266 (2) ◽  
pp. H714-H719 ◽  
Author(s):  
S. Verma ◽  
J. H. McNeill
Keyword(s):  
Isolated Heart ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Diabetic Rat ◽  
Metformin Hydrochloride ◽  
Ventricular Contractility ◽  
Glucose Levels ◽  
Rat Hearts ◽  
Plasma Insulin Levels ◽  
Developed Pressure

The effects of metformin administration were studied in isolated perfused working hearts from control and diabetic rats. Control and streptozotocin-treated diabetic rats were treated for 8 wk with metformin hydrochloride. Treatment was initiated at 350 mg.kg-1 x day-1 and was gradually increased to a dose of 650 mg.kg-1 x day-1, which was maintained over a 6-wk period. Isolated heart performance was assessed under conditions of increasing preload to evaluate the performance of each heart to “stress.” Hearts from untreated diabetic rats exhibited a depressed response to increases in left atrial filling pressures from 17.5 to 22.5 cmH2O in terms of left ventricular developed pressure, ventricular contractility, and ventricular relaxation compared with age-matched untreated controls. The diabetic hearts also exhibited a delayed half time to relaxation at filling pressures from 15 to 22.5 cmH2O. The function curves were performed at a constant heart rate of 300 beats/min. These responses were restored to control values in diabetic rats treated with metformin. Metformin treatment did not affect the ventricular responses in control rats. Metformin reduced plasma glucose levels in the diabetic rats from 24.3 to 14.4 mM without any increase in the plasma insulin levels. The diabetic group had higher triglycerides than age-matched untreated control rats, and metformin administration in diabetic rats reduced triglyceride levels to control values but had no effect in control rats. In conclusion, metformin administration improves cardiac performance in streptozotocin-diabetic rats under conditions of increasing preload.

Differential autocrine modulation of atrial and ventricular potassium currents and of oxidative stress in diabetic rats

2006 ◽  
Vol 290 (5) ◽  
pp. H1879-H1888 ◽  
Author(s):  
Yakhin Shimoni ◽  
Don Hunt ◽  
Keyun Chen ◽  
Teresa Emmett ◽  
Gary Kargacin
Keyword(s):  
Oxidative Stress ◽  
Renin Angiotensin System ◽  
Cell Voltage ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Ang Ii ◽  
A Cells ◽  
Ras Activation ◽  
Rat Hearts

The autocrine modulation of cardiac K+ currents was compared in ventricular and atrial cells (V and A cells, respectively) from Type 1 diabetic rats. K+ currents were measured by using whole cell voltage clamp. ANG II was measured by ELISA and immunofluorescent labeling. Oxidative stress was assessed by immunofluorescent labeling with dihydroethidium, a measure of superoxide ions. In V cells, K+ currents are attenuated after activation of the renin-angiotensin system (RAS) and the resulting ANG II-mediated oxidative stress. In striking contrast, these currents are not attenuated in A cells. Inhibition of the angiotensin-converting enzyme (ACE) also has no effect, in contrast to current augmentation in V cells. ANG II levels are enhanced in V, but not in A, cells. However, the high basal ANG II levels in A cells suggest that in these cells, ANG II-mediated pathways are suppressed, rather than ANG II formation. Concordantly, superoxide ion levels are lower in diabetic A than in V cells. Several findings indicate that high atrial natriuretic peptide (ANP) levels in A cells inhibit RAS activation. In male diabetic V cells, in vitro ANP (300 nM–1 μM, >5 h) decreases oxidative stress and augments K+ currents, but not when excess ANG II is present. ANP has no effect on ventricular K+ currents when the RAS is not activated, as in control males, in diabetic males treated with ACE inhibitor and in diabetic females. In conclusion, the modulation of K+ currents and oxidative stress is significantly different in A and V cells in diabetic rat hearts. The evidence suggests that this is largely due to inhibition of RAS activation and/or action by ANP in A cells. These results may underlie chamber-specific arrhythmogenic mechanisms.

Therapeutic Application of Diacylglycerol Oil for Obesity: Serotonin Hypothesis

2012 ◽  
Vol 2 (1) ◽  
pp. 1 ◽  
Author(s):  
Hidekatsu Yanai ◽  
Hiroshi Yoshida ◽  
Yuji Hirowatari ◽  
Norio Tada
Keyword(s):  
Energy Expenditure ◽  
Molecular Mechanisms ◽  
Uncoupling Protein ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serotonin Release ◽  
Intestinal Cell ◽  
Therapeutic Application ◽  
Postprandial Triglyceride

Characteristics for the serum lipid abnormalities in the obesity/metabolic syndrome are elevated fasting, postprandial triglyceride (TG), and decreased high-density lipoprotein-cholesterol (HDL-C). Diacylglycerol (DAG) oil ingestion has been reported to ameliorate postprandial hyperlipidemia and prevent obesity by increasing energy expenditure, due to the intestinal physiochemical dynamics that differ from triacylglycerol (TAG). Our study demonstrated that DAG suppresses postprandial increase in TG-rich lipoprotein, very low-density lipoprotein (VLDL), and insulin, as compared with TAG in young, healthy individuals. Interestingly, our study also presented that DAG significantly increases plasma serotonin, which is mostly present in the intestine, and mediates thermogenesis, proposing a possible mechanism for a postprandial increase in energy expenditure by DAG. Our other study demonstrated that DAG suppresses postprandial increase in TG, VLDL-C, and remnant-like particle-cholesterol, in comparison with TAG in an apolipoprotein C-II deficient subject, suggesting that DAG suppresses postprandial TG-rich lipoprotein independently of lipoprotein lipase. Further, to understand the molecular mechanisms for DAG-mediated increase in serotonin and energy expenditure, we studied the effects of 1-monoacylglycerol and 2-monoacylglycerol, distinct digestive products of DAG and TAG, respectively, on serotonin release from the Caco-2 cells, the human intestinal cell line. We also studied effects of 1- and 2-monoacylglycerol, and serotonin on the expression of mRNA associated with β-oxidation, fatty acids metabolism, and thermogenesis, in the Caco-2 cells. 1-monoacylglycerol significantly increased serotonin release from the Caco-2 cells, compared with 2-monoacylglycerol by approximately 40%. The expression of mRNA of acyl-CoA oxidase (ACO), fatty acid translocase (FAT), and uncoupling protein-2 (UCP-2), was significantly higher in 1-MOG-treated Caco-2 cells, than 2-MOG-treated cells. The expression of mRNA of ACO, medium-chain acyl-CoA dehydrogenase, FAT, and UCP-2, was significantly elevated in serotonin-treated Caco-2 cells, compared to cells incubated without serotonin. In conclusion, our clinical and in vitro studies suggested a possible therapeutic application of DAG for obesity, and obesity-related metabolic disorders.Key words: Diacylglycerol, intestine, obesity, serotonin, thermogenesis

Antidyslipidemic and Antioxidant Activities of Matricaria pubescens (Desf.) Shultz.in Streptozotocin-Induced Diabetic Rats

2020 ◽  
Vol 18 ◽  
Author(s):  
Ayoub Amssayef ◽  
Bouchra Azzaou ◽  
Mohammed Ajebli ◽  
Mohamed Eddouks
Keyword(s):  
Antioxidant Activity ◽  
Antioxidant Activities ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Diabetic Rats ◽  
Favorable Effect ◽  
Lipoprotein Profile ◽  
Phytochemical Compounds ◽  
Asteraceae Family

Aims: The study aimed to evaluate the antihyperlipidemic and antioxidant activities of Matricaria pubescens. Background: Matricaria pubescens (Desf.) Shultz belongs to Asteraceae family and it is commonly used traditionally for handling diabetes mellitus. Objective: The objective of this study was to assess the antioxidant activity of Matricaria pubescens (Desf.) Shultz and its effect on lipid and lipoprotein profile in normal and streptozotocin-induced diabetic rats. Methods: The effect of repeated (7 days of treatment) oral administration of the aqueous extract of aerial part of Matricaria pubescens (MPAE) at a dose of 40 mg/kg on lipid and lipoprotein profile was examined in normal and streptozotocin-induced diabetic rats. Furthermore, a preliminary phytochemical screening and the quantification of phenolic, flavonoid and tannin contents as well as the antioxidant activity using two methods (FRAP and ABTS) were carried out. Results: MPAE demonstrated a potent antidyslipidemic effect in diabetic rats by reducing serum levels of triglycerides, total cholesterol and low-density lipoprotein (LDL). In addition, the results showed that the extract is rich in several phytochemical compounds and revealed an important antioxidant activity. Conclusion: In summary, this study proved that Matricaria pubescens (Desf.) Shultz. has a favorable effect on diabetic dyslipidemia.

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