P75Shortening and calcium transport in epicardial and endocardial ventricular myocytes from the streptozotocin-induced diabetic rat

Bariatric surgery has been reported to relieve diabetic cardiomyopathy (DCM) effectively. However, the mechanisms remain largely unknown. To determine the effects of bariatric surgery on DCM via modulation of myocardial Ca2+ homeostasis and autophagy, sleeve gastrectomy (SG), duodenal-jejunal bypass (DJB), and sham surgeries were performed in diabetic rats induced by high-fat diet and a low dose of streptozotocin. Cardiac remodeling was assessed by a series of morphometric and histological analyses. Transthoracic echocardiography and hemodynamic measurements were performed to determine cardiac function. Ca2+ homeostasis was evaluated by measuring Ca2+ transients with fura-2 AM in isolated ventricular myocytes along with detection of the abundance of Ca2+ regulatory proteins in the myocardium. Myocardial autophagic flux was determined by expression of autophagy-related proteins in the absence and presence of chloroquine. Both SG and DJB surgery alleviated DCM morphologically and functionally. Ca2+ transients exhibited a significantly higher amplitude and faster decay after SG and DJB, which could be partially explained by increased expression of ryanodine receptor 2, sarco(endo)plasmic reticulum Ca2+-2ATPase, 12.6-kDa FK506-binding protein, and hyperphosphorylation of phospholamban. In addition, a lower level of light chain 3B and higher level of p62 were detected after both SG and DJB, which was not reversed by chloroquine treatment and associated with activated mammalian target of rapamycin and attenuated AMP-activated protein kinase signaling pathway. Collectively, these results provided evidence that bariatric surgery could alleviate DCM effectively, which may result, at least in part, from facilitated Ca2+ homeostasis and attenuated autophagy, suggesting a potential choice for treatment of DCM when properly implemented. NEW & NOTEWORTHY The present study is the first to investigate the modulation of myocardial Ca2+ homeostasis and autophagy after bariatric surgery and to examine its effects on diabetic cardiomyopathy. Bariatric surgery could facilitate myocardial Ca2+ homeostasis and attenuate myocardial autophagy, contributing to the alleviation of cardiomyopathy morphologically and functionally in a diabetic rat model.

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Intracellular protons inhibit transient outward K+ current in ventricular myocytes from diabetic rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1996.271.5.h2154 ◽

1996 ◽

Vol 271 (5) ◽

pp. H2154-H2161 ◽

Cited By ~ 7

Author(s):

Z. Xu ◽

K. P. Patel ◽

G. J. Rozanski

Keyword(s):

Ventricular Myocytes ◽

External Solution ◽

Cell Voltage ◽

Diabetic Rats ◽

Diabetic Rat ◽

Intracellular Acidosis ◽

K Current ◽

Acid Load ◽

Dimethyl Amiloride ◽

And Control

This study examined the effects of protons on cardiac ion channel function in early stages of diabetes mellitus. Transient outward (I(to)) and inward rectifier K+ (IK1) currents were recorded by the whole cell, voltage-clamp technique in ventricular myocytes isolated from hearts of streptozotocin-induced diabetic and control rats. Proton concentration was controlled by independently varying the pH of buffered external or pipette (pHp) solutions. External acidification did not alter I(to) in diabetic rat myocytes when initiated after intracellular dialysis with standard pHp 7.2, but when these cells were dialyzed with acidic pHp (6.6 or 6.0), I(to) density was significantly reduced. Low pHp also reduced I(to) density more in cells from diabetic rats than in controls, whereas alkaline pHp had no effect on either group of cells compared with standard pHp 7.2. In control myocytes dialyzed with pHp 6.0, block of Na+/H+ exchange with 5-(N,N-dimethyl)-amiloride (DMA) or Na(+)-free external solution further reduced I(to) density compared with pHp 6.0 alone, whereas these treatments had less effect on acid-dialyzed cells from diabetic rats. Dialysis with pHp to 6.0 did not alter IK1 in either group of cells compared with standard pHp 7.2, but when done in the presence of DMA or Na(+)-free conditions, IK1 density in both groups was significantly reduced by nearly the same amount. We conclude that intracellular protons inhibit I(to) channels in ventricular myocytes from diabetic and control rats, but that for a given acid load, inhibition is markedly greater in diabetics. This difference may be explained by a diabetes-induced decrease in Na+/H+ exchange that limits proton extrusion during intracellular acidosis. Moreover, acidosis may differentially suppress I(to) and IK1, suggesting that these K+ channels exhibit dissimilar sensitivities to intracellular protons.

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Effects of Pioglitazone on Ventricular Myocyte Shortening and Ca2+ Transport in the Goto-Kakizaki Type 2 Diabetic Rat

Physiological Research ◽

10.33549/physiolres.933567 ◽

2018 ◽

pp. 57-68 ◽

Cited By ~ 1

Author(s):

K. A. SALEM ◽

V. SYDORENKO ◽

M. QURESHI ◽

M. OZ ◽

F. C. HOWARTH

Keyword(s):

Ventricular Myocytes ◽

Cellular Level ◽

Diabetic Rat ◽

Antidiabetic Agent ◽

Inotropic Effects ◽

And Control ◽

Transmembrane Currents ◽

Negative Inotropic Effects ◽

Type 2 Diabetic

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.

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Role of Potassium Currents in the Formation of After-Hyperpolarization Phase of Extracellular Action Potentials Recorded from the Control and Diabetic Rat Heart Ventricular Myocytes

Journal of Evolutionary Biochemistry and Physiology ◽

10.1134/s0022093021060272 ◽

2021 ◽

Vol 57 (6) ◽

pp. 1511-1521

Author(s):

I. V. Kubasov ◽

A. V. Stepanov ◽

A. A. Panov ◽

O. V. Chistyakova ◽

I. B. Sukhov ◽

...

Keyword(s):

Rat Heart ◽

Action Potentials ◽

Ventricular Myocytes ◽

Potassium Currents ◽

Diabetic Rat

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Effects of Vitamin D and Its Metabolites on Calcium Transport in the Diabetic Rat

Endocrinology ◽

10.1210/endo-99-3-793 ◽

1976 ◽

Vol 99 (3) ◽

pp. 793-799 ◽

Cited By ~ 36

Author(s):

LOUIS E. SCHNEIDER ◽

JACK OMDAHL ◽

HAROLD P. SCHEDL

Keyword(s):

Vitamin D ◽

Calcium Transport ◽

Diabetic Rat

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Myofilament Ca2+ sensitivity in ventricular myocytes from streptozotocin-induced diabetic rat

International Journal of Diabetes and Metabolism ◽

10.1159/000497543 ◽

2001 ◽

Vol 9 (3) ◽

pp. 67-74 ◽

Cited By ~ 2

Author(s):

Howarth F.C. ◽

Qureshi M.A.

Keyword(s):

Ventricular Myocytes ◽

Diabetic Rat

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Metabolic basis of decreased transient outward K+ current in ventricular myocytes from diabetic rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1996.271.5.h2190 ◽

1996 ◽

Vol 271 (5) ◽

pp. H2190-H2196 ◽

Cited By ~ 12

Author(s):

Z. Xu ◽

K. P. Patel ◽

G. J. Rozanski

Keyword(s):

Ventricular Myocytes ◽

Cell Voltage ◽

Diabetic Rats ◽

K Channel ◽

Diabetic Rat ◽

Channel Function ◽

Early Stages ◽

Metabolic Basis ◽

External Glucose

The purpose of this study was to examine the mechanisms of alterations in cardiac K+ channel function in early stages of experimental diabetes mellitus induced by streptozotocin. Transient outward (Ito) and inward rectifier (IK1) K+ currents were recorded by the whole cell voltage-clamp technique in ventricular myocytes isolated from hearts of 2- to 4-wk diabetic and age-matched control rats. Ito density in myocytes from diabetic rats was approximately 30% less than control (at +60 mV; P < 0.01) under basal recording conditions in the presence of 18 mM external glucose, whereas IK1 density was not different between groups. When external glucose concentration was decreased to 5 mM for 4-6 h, basal Ito density was not changed in either group of myocytes. To further examine the possible metabolic basis of reduced Ito density in myocytes from diabetic rats, we separately tested three structurally different compounds that affect substrate utilization in cardiac myocytes: insulin (0.1 microM), dichloroacetate (1.5 mM), and L-carnitine (10 mM). Each compound completely normalized Ito density in myocytes from diabetic rats treated in vitro for 4-6 h. The same agents had no effect on Ito density in control myocytes, nor was IK1 altered in either group of cells. These data provide the first evidence to support the hypothesis that there is a metabolic basis for decreased Ito density in diabetic rat ventricular myocytes in early stages of this model. Furthermore, our data suggest that depressed glucose metabolism in the diabetic heart may be a key factor underlying changes in Ito channel function, because agents that increase glucose utilization normalize Ito density within a short time period.

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