scholarly journals Reduction in the Amplitude of Shortening and Ca2+ Transient by Phlorizin and Quercetin-3-O-Glucoside in Ventricular Myocytes From Streptozotocin-Induced Diabetic Rats

2016 ◽  
pp. 239-250 ◽  
Author(s):  
N. N. HAMOUDA ◽  
M. A. QURESHI ◽  
J. M. ALKAABI ◽  
M. OZ ◽  
F. C. HOWARTH

Diabetes mellitus is the leading cause of cardiovascular morbidity and mortality. Phlorizin (PHLOR) and quercetin-3-O-glucoside (QUER-3-G) are two natural compounds reported to have antidiabetic properties by inhibiting sodium/glucose transporters. Their effects on ventricular myocyte shortening and intracellular Ca2+ in streptozotocin (STZ)-induced diabetic rats were investigated. Video edge detection and fluorescence photometry were used to measure ventricular myocyte shortening and intracellular Ca2+, respectively. Blood glucose in STZ rats was 4-fold higher (469.64±22.23 mg/dl, n=14) than in Controls (104.06±3.36 mg/dl, n=16). The amplitude of shortening was reduced by PHLOR in STZ (84.76±2.91 %, n=20) and Control (83.72±2.65 %, n=23) myocytes, and by QUER-3-G in STZ (79.12±2.28 %, n=20) and Control (76.69±1.92 %, n=30) myocytes. The amplitude of intracellular Ca2+ was also reduced by PHLOR in STZ (82.37±3.16 %, n=16) and Control (73.94±5.22 %, n=21) myocytes, and by QUER-3-G in STZ (73.62±5.83 %, n=18) and Control (78.32±3.54 %, n=41) myocytes. Myofilament sensitivity to Ca2+ was not significantly altered by PHLOR; however, it was reduced by QUER-3-G modestly in STZ myocytes and significantly in Controls. PHLOR and QUER-3-G did not significantly alter sarcoplasmic reticulum Ca2+ in STZ or Control myocytes. Altered mechanisms of Ca2+ transport partly underlie PHLOR and QUER-3-G negative inotropic effects in ventricular myocytes from STZ and Control rats.

2018 ◽  
pp. 57-68 ◽  
Author(s):  
K. A. SALEM ◽  
V. SYDORENKO ◽  
M. QURESHI ◽  
M. OZ ◽  
F. C. HOWARTH

Pioglitazone (PIO) is a thiazolidindione antidiabetic agent which improves insulin sensitivity and reduces blood glucose in experimental animals and treated patients. At the cellular level the actions of PIO in diabetic heart are poorly understood. A previous study has demonstrated shortened action potential duration and inhibition of a variety of transmembrane currents including L-type Ca2+ current in normal canine ventricular myocytes. The effects of PIO on shortening and calcium transport in ventricular myocytes from the Goto-Kakizaki (GK) type 2 diabetic rat have been investigated. 10 min exposure to PIO (0.1-10 µM) reduced the amplitude of shortening to similar extents in ventricular myocytes from GK and control rats. 1 μM PIO reduced the amplitude of the Ca2+ transients to similar extents in ventricular myocytes from GK and control rats. Caffeine-induced Ca2+ release from the sarcoplasmic reticulum and recovery of Ca2+ transients following application of caffeine and myofilament sensitivity to Ca2+ were not significantly altered in ventricular myocytes from GK and control rats. Amplitude of L-type Ca2+ current was not significantly decreased in myocytes from GK compared to control rats and by PIO treatment. The negative inotropic effects of PIO may be attributed to a reduction in the amplitude of the Ca2+ transient however, the mechanisms remain to be resolved.


1992 ◽  
Vol 70 (1) ◽  
pp. 13-19 ◽  
Author(s):  
Eve L. Warner ◽  
Franco Galasso ◽  
Carl I. Thompson ◽  
Francis L. Belloni

To determine the vasodilative and negative inotropic effects of adenosine in hearts of diabetic rats, isolated hearts, perfused at constant perfusion pressure (Langendorff technique), were prepared from age-matched control Wistar rats and rats made diabetic 10 weeks prior to study by a single injection of streptozotocin (65 mg∙kg−1, i.p.). Adenosine and nitroprusside each increased coronary inflow when administered either as bolus injections or as infusions. Coronary flow responses to nitroprusside were unchanged in diabetic hearts. Coronary flow responses of diabetic hearts to adenosine injections were unchanged, but responses to adenosine infusions tended to be larger than in normal hearts. Diabetes had no significant effect on the EC50 for either vasodilator. Adenosine inhibited the inotropic effect of isoproterenol (enhanced left ventricular (LV) pressure (P) and LV dP/dtmax) in normal hearts, independently of its vasodilative action. This negative inotropic action of adenosine appeared equally strong in diabetic hearts. We conclude that adenosine's coronary vasodilative and anti-β-adrenergic, negative inotropic effects in the rat heart were not diminished after 10 weeks of streptozotocin-induced diabetes mellitus. Thus, earlier reports of diminished adenosine dilative efficacy in experimental diabetes may have been unique to those particular models.Key words: experimental diabetes mellitus, coronary, adenosine, isoproterenol, myocardial contraction.


2000 ◽  
Vol 93 (4) ◽  
pp. 1034-1044 ◽  
Author(s):  
Lucinda A. Davies ◽  
Clare N. Gibson ◽  
Mark R. Boyett ◽  
Philip M. Hopkins ◽  
Simon M. Harrison

Background The aim of this study was to describe and compare the effects of isoflurane, sevoflurane, and halothane at selected concentrations (i.e., concentrations that led to equivalent depression of the electrically evoked Ca2+ transient) on myofilament Ca2+ sensitivity, sarcoplasmic reticulum (SR) Ca2+ content, and the fraction of SR Ca2+ released during electrical stimulation (fractional release) in rat ventricular myocytes. Methods Single rat ventricular myocytes loaded with fura-2 were electrically stimulated at 1 Hz, and the Ca2+ transients and contractions were recorded optically. Cells were exposed to each anesthetic for 1 min. Changes in myofilament Ca2+ sensitivity were assessed by comparing the changes in the Ca2+ transient and contraction during exposure to anesthetic and low Ca2+. SR Ca2+ content was assessed by exposure to 20 mm caffeine. Results Isoflurane and halothane caused a depression of myofilament Ca2+ sensitivity, unlike sevoflurane, which had no effect on myofilament Ca2+ sensitivity. All three anesthetics decreased the electrically stimulated Ca2+ transient. SR Ca2+ content was reduced by both isoflurane and halothane but was unchanged by sevoflurane. Fractional release was reduced by both isoflurane and sevoflurane, but was unchanged by halothane. Conclusions Depressed myofilament Ca2+ sensitivity contributes to the negative inotropic effects of isoflurane and halothane but not sevoflurane. The decrease in the Ca2+ transient is either responsible for or contributory to the negative inotropic effects of all three anesthetics and is either primarily the result of a decrease in fractional release (isoflurane and sevoflurane) or primarily the result of a decrease in SR Ca2+ content (halothane).


Author(s):  
Mutiara Indah Sari ◽  
Maya Anjelir Antika ◽  
Dwi Rita Anggraini

 Objective: Lawsonia inermis (Linn.) leaves are one of the alternative medicines to treat diabetes mellitus in Indonesia. We investigated the blood glucose level (BGL) of the L. inermis (Linn.) leaves ethanolic extract (LLEE) leaves and evaluated the histopathological alterations in diabetic rats.Methods: This study was an experimental study with posttest - only control group design. Alloxan (120 mg/kg, intraperitoneally)-induced diabetic rats. 35 of Wistar rats (Rattus norvegicus) were divided randomly into five groups, i.e. K: Normal control, P1: Diabetic control, and P2, P3, and P4 (200 mg/kg body weight [BW], 400 mg/kg BW, and 600 mg/kg BW of LLEE, orally) for 28 days. At the end of the treatment, the rats were sacrificed to obtain the kidney for histopathological evaluation using hematoxylin and eosin technique. BGLs were conducted using a glucose meter (GlucoDR).Results: One-way ANOVA test showed that dose 400 mg/kg BW of the LLEE was related to BGL of alloxan-induced diabetic rats (p=0.000). The histopathological of kidney showed glomerular inflammation (GI), epithelial membrane lining degeneration, vascular congestion, and interstitial tubule hemorrhage at diabetic control (P1). Meanwhile, treated with 600 mg/kg BW of LLEE (P4) showed increase cellular regeneration as normal architecture of the kidney.Conclusion: The LLEE at dose 400 mg/kg BW effective decreased BGL and was able to restore the kidney destruction of alloxan-induced diabetic rats at dose 600 mg/kg BW.


2004 ◽  
Vol 101 (5) ◽  
pp. 1145-1152 ◽  
Author(s):  
Julien Amour ◽  
Jean-Stéphane David ◽  
Benoît Vivien ◽  
Pierre Coriat ◽  
Bruno Riou

Background Halogenated anesthetics potentiate the positive inotropic effects of alpha- and beta-adrenoceptor stimulations. Although diabetes mellitus induces significant myocardial abnormalities, the interaction of halogenated anesthetics and adrenoceptor stimulation in diabetic myocardium remains unknown. Methods Left ventricular papillary muscles were provided from healthy and streptozotocin-induced diabetic rats. Effects of 1 minimum alveolar concentration halothane, isoflurane, and sevoflurane on the inotropic and lusitropic responses of alpha (phenylephrine)- and beta (isoproterenol)-adrenoceptor stimulations were studied at 29 degrees C with 12 pulses/min. Data shown are mean percentage of baseline active force +/- SD. Results Phenylephrine induced comparable positive inotropic effects in healthy and diabetic rats (143 +/- 8 vs. 136 +/- 18%; not significant), but the potentiation by halogenated anesthetics was abolished in the diabetic rats (121 +/- 20, 130 +/- 20, and 123 +/- 20% for halothane, isoflurane, and sevoflurane, respectively; not significant). In diabetic rats, the positive inotropic effect of isoproterenol was markedly diminished (109 +/- 9 vs. 190 +/- 18%; P < 0.05), but its potentiation was preserved with isoflurane (148 +/- 21%; P < 0.05) and sevoflurane (161 +/- 40%; P < 0.05) but not with halothane (126 +/- 16%; not significant). Halothane induced a deleterious effect on the sarcoplasmic reticulum, as shown by its impairment in the lusitropic effect of isoproterenol, compared with isoflurane and sevoflurane. Conclusion Potentiation of the positive inotropic effect of alpha-adrenoceptor stimulation by halogenated anesthetics is abolished in diabetic rats. In contrast, potentiation of beta-adrenoceptor stimulation is preserved with isoflurane and sevoflurane but not with halothane, probably because of its deleterious effects on sarcoplasmic reticulum.


2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Daniel U. Owu ◽  
Agona O. Obembe ◽  
Chukwuemeka R. Nwokocha ◽  
Ime E. Edoho ◽  
Eme E. Osim

The effect of vitamin C administration on gastric acid secretion and ulcer in diabetic rats was studied. Vitamin C (200 mg/kg b.w.) was administered to both streptozotocin-induced diabetic and control groups orally for 28 days. Gastric acid secretion was measured and ulcer was induced using ethanol. Histological changes were observed in the stomach. Basal and stimulated acid secretion in diabetic control rat was significantly () decreased when compared to vitamin C-treated diabetic group and control. Administration of vitamin C significantly () increased the histamine-stimulated gastric acid secretion in diabetics than control while reduction in gastric secretion by ranitidine was similar compared with control. Vitamin C treatment significantly () reduced ulcer index in diabetic group and increased mucus weight when compared with diabetic group which was also confirmed with photomicrographs. The mean body weight of diabetic rats treated with vitamin C was comparable to the control. The blood glucose level was significantly () reduced in diabetic group given vitamin C ( mMol/L) compared to the diabetic control ( g). It is concluded that vitamin C is beneficial in improving gastric acid secretion and protects against ulceration in streptozotocin-induced diabetes mellitus in rats due to its antioxidant potential.


2021 ◽  
pp. 787-792
Author(s):  
Zainab k. Hussain ◽  
Jabbar H. Yenzeel ◽  
Hayfa H. Hassani

To study the genetic effect of gestational diabetes mellitus by study IRS1gene expression in female with Gestational diabetes mellitus. It is characterized high level of blood glucose, especially during first trimester then increased during the 2nd and 3rd trimester of the pregnancy period. The blood samples taken from one hundred twenty healthy women and female with gestational diabetes mellitus in 3rd trimester period of pregnancy, level of fasting blood glucose (FBG) also HbA1c% measured to diagnose GDM, in addition to lipid profile (cholesterol, triglyceride, HDL, LDL, and VLDL), molecular study consist of RNA extraction and qRT- PCR for IRS1gene expression determination. The fasting blood glucose mg/dl and HbA1c% level was increased highly significantly (P<0.01) between patients and control (healthy women) in 3rd trimester stage in addition lipid profile included )serum cholesterol, serum triglyceride, LDL and VLDL( (mg/dl) but level of HDL (mg/dl) was decreased highly significantly (P<0.01) between patients and control. The result showed high significant of IRS1 expression gene in control (1.00 ± 0.00) while in patients (0.147 ± 0.02). The low expression of IRS1 gene was connected with gestational diabetes mellitus comparison in control (healthy women) in Iraqi female in third trimester of pregnancy


2018 ◽  
Vol 1 (8) ◽  
pp. 86
Author(s):  
Preeya Dat-arun ◽  
Rattana Leelawattana ◽  
Pavinee Chinachoti

Background: Diabetes mellitus (DM) is a major health care problem worldwide.  Major intervention control of DM is by using medical treatments and dietetic therapy.  Spices and herbs have been known to have anti-oxidant, anti-inflammation and anti-diabetic properties. Southern Thai foods known to contain phytochemicals in large amount, have been demonstrated to exhibit such properties and Namya Kanom Jeen (NKJ), a Southern Thai soup, shown to be most promising.  Here, we studied the effect of NKJ water extracts on hypoglycemic and anti-oxidant properties in Alloxan-induced diabetic rats.Methods: This study aimed to assess the effect of NKJ water extract on blood glucose, insulin, malondialdehyde (MDA), homeostatic model assessment of insulin resistance (HOMA-IR) and high sensitive C-reactive protein (hs-CRP) levels in Alloxan-induced diabetic (DM) rats for 3 weeks.Results: In Alloxan-induced diabetic rats, the NKJ water soluble extracts at 200, 1,000 and 2,000 mg/kg body weight doses (n=7) significantly lowered blood glucose, insulin, MDA, HOMA-IR levels compared to diabetic control (Metformin, p < 0.05). Conclusion: In summary, feeding of NKJ aqueous extract effectively lowered baseline blood glucose, insulin, MDA and HOMA-IR in diabetic rats.Keywords: Diabetes mellitus; Anti-oxidant; Glycemic; Insulin resistance; HOMA-IR, Namya Kanom Jeen powder 


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A439-A439
Author(s):  
Yoshiyu Takeda ◽  
Yoshimichi Takeda ◽  
Masashi Demura ◽  
Mitsuhiro Kometani ◽  
Shigehiro Karashima ◽  
...  

Abstract Objective: The renoprotective effect of sodium glucose cotransporter 2 inhibitor (SGL2i) has been reported in diabetic patients. Local renin-angiotensin-aldosterone system (RAAS) is activated in diabetes mellitus and hypertension. We examined the effects of SGL2i on the RAAS in the obese diabetic rats fed a high salt diet. Methods: Zucker-diabetic rats (ZDR) and control rats were fed a high or normal salt diet and were treated with canagliflozin for 8 weeks. Blood pressure (BP), blood glucose (BG), PRA, plasma aldosterone (PAC), urinary albumin excretion (UAE), urinary 8-hydroxy-2’-deoxyguanosine (8-OHdG), gene expression of angiotensinogen in the kidney were measured. Results: ZDR febd a high salt diet showed high BP, increased UAE and urinary 8-OHdG and elevated angiotensinogen mRNA levels. Treatment with canagliflozin significantly decreased BP, BG, UAE, urinary 8-OHdG and and renal angiotensinogen mRNA levels compared with control rats (p&lt0.05). Discussion and Conclusion: The closer mechanism of renoptotection of SGL2i in diabetes mellitus is unclear. We have reported that the repoprotective effects of type 2 angiotensin receptor antagonist or mineralocorticoid receptor blocker were partly due to the decreased RAAS in the kidney. Decreased renal RAAS by the treatment with canagliflozin may contribute to the renoprotection in DZR.


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