scholarly journals Reduced expression of HCN channels in the sinoatrial node of streptozotocin-induced diabetic rats

2017 ◽  
Vol 95 (5) ◽  
pp. 586-594 ◽  
Author(s):  
Xin Huang ◽  
Nier Zhong ◽  
Hong Zhang ◽  
Aiqun Ma ◽  
Zuyi Yuan ◽  
...  
Keyword(s):  
Sinoatrial Node ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Electrical Remodeling ◽  
Hcn Channels ◽  
Conduction Time ◽  
Hcn Channel ◽  
Diastolic Depolarization

Diabetes mellitus (DM) is associated with an electrical remodeling of the heart, increasing the risk of arrhythmias. However, knowledge of electrical remodeling in the sinoatrial node (SAN) by DM is limited. We investigated the expression of HCN channel isoforms, HCN1–HCN4, in SAN from streptozotocin (STZ)-induced diabetic rats and the age-matched controls. We found that the STZ-induced diabetic rats have a lower intrinsic heart rate, a lengthened sinoatrial conduction time, and rate-corrected maximal sinoatrial node recovery time in vivo as well as a longer cycle length (CL) in vitro, as compared with the control. Optical mapping of the SAN demonstrated an inferior leading pacemaker site, reduced SAN conduction velocity and diastolic depolarization slope, and a longer action potential duration in the STZ-induced diabetic rats than in the control. The transcripts and proteins of HCN2 and HCN4 in diabetic SAN were reduced. Specific blockade of HCN channels by 3 μmol/L ivabradine significantly prolonged the CL of a Langendorff heart by 18% in the diabetic rats and 26% in the control. The reduced expression of HCN channel isoforms in the SAN of the STZ-induced diabetic rat may be an important contributor to the reduced SAN function in DM.

Regulation of hepatic triiodothyronine production in the streptozotocin-induced diabetic rat

1984 ◽  
Vol 247 (4) ◽  
pp. E526-E533
Author(s):  
A. S. Jennings
Keyword(s):  
Diabetic Rats ◽  
Diabetic Rat ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Insulin Administration ◽  
Progressive Decline ◽  
Serum T4 ◽  
Fasted Rats

The effect of diabetes on 3,5,3'-triiodothyronine (T3) production was determined in the isolated perfused rat liver. Induction of diabetes with streptozotocin resulted in decreased serum thyroxine (T4) and T3 levels and a progressive decline in hepatic T3 production over 5 days. The decline in T3 production resulted from decreased conversion of T4 to T3, whereas T4 uptake was unchanged. Insulin administration restored serum T4 and T3, hepatic conversion of T4 to T3, and T3 production to normal levels. When serum T4 levels in diabetic rats were maintained by T4 administration, the conversion of T4 to T3 and T3 production returned to control levels. However, restoration of serum T4 levels in fasted rats failed to correct the decrease in hepatic T4 uptake or T3 production. Glucagon, at supraphysiological concentrations in vitro and in vivo, slightly decreased T4 uptake and T3 production without altering the conversion of T4 to T3. These data suggest that the fall in serum T4 levels observed in diabetic rats is important in mediating the decreased hepatic conversion of T4 to T3 and T3 production.

In vivo and in vitro resistance to maximal insulin-stimulated glucose disposal in insulin deficiency

1985 ◽  
Vol 249 (3) ◽  
pp. E312-E316 ◽  
Author(s):  
E. Dall'Aglio ◽  
H. Chang ◽  
C. B. Hollenbeck ◽  
C. E. Mondon ◽  
C. Sims ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Glucose Transport ◽  
Diabetic Rats ◽  
Glucose Disposal ◽  
Diabetic Rat ◽  
Insulin Deficiency ◽  
Fat Cell ◽  
Total Body

The effect of streptozotocin-induced diabetes mellitus on maximal insulin-stimulated glucose uptake in the rat was studied in isolated adipocyte, perfused hindlimb, and the intact organism. Basal glucose transport per fat cell was reduced by approximately two-thirds (P less than 0.001), being associated with a similar decrease in glucose oxidation per fat cell (P less than 0.001). There was also a significant decrease (P less than 0.001) in basal glucose uptake by perfused hindlimb of diabetic rats of approximately 40%. Furthermore, maximal insulin-stimulated glucose transport and oxidation were approximately 50% lower (P less than 0.001) in fat cells of diabetic as compared with control rats. In contrast, maximal insulin-stimulated glucose disposal by perfused hindlimbs from diabetic and control rats was similar, and this was also true of the ability of insulin to maximally stimulate glucose uptake in the intact normal and diabetic rat. These findings indicate that variation exists in the manner in which insulin-sensitive tissues respond to experimentally induced insulin deficiency and support the view that total body glucose disposal is primarily related to insulin action on muscle.

scholarly journals Stellaria media attenuates the hyperglycemia and hyperlipidemia in alloxan-induced diabetic rat

2019 ◽  
Vol 14 (2) ◽  
pp. 80-86 ◽  
Author(s):  
Rahmat Khan ◽  
Wasim Ahmad ◽  
Mushtaq Ahmed
Keyword(s):  
Research Work ◽  
Diabetic Control ◽  
Experimental Models ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Serum Enzyme ◽  
Stellaria Media ◽  
Diabetic Treatment

Abstract The objective of this research work was to assess the hyperglycemic and hyperlipidemiceffects of Stellaria media in alloxan induced diabetic rats using different experimental models. Standard documented protocols were used to concede the in vitro and in vivo activities. Biochemical markers studies were also done. The results of the study showed strong pancreatic α-amylase and β-glucosidase inhibition in-vitroat varying concentrations of the extract which further validated the in-vivo anti-diabetic action of the plant because of the inhibition of the above enzymes.The administration of various concentrations of the extract showedmomentous decrease in fasting blood level when compared to diabetic control. Similarly, remarkably improved hemoglobin (+20.10%), and decreased HbA1c (−48.44%) was observed when compared to diabetic control rats. The extract also caused reduced serum enzyme (ALT, ALP, bilirubin) levels and produced a succeeding recovery toward their normal values.It can be concluded from these investigations that the in-vitro and in-vivo hypoglycemic and hypolipidemic activity offers the methodicaljustification for the use of S. media in herb based anti-diabetic treatment.

scholarly journals Adiponectin Modified BMSCs Alleviate Heart Fibrosis via Inhibition TGF-beta1/Smad in Diabetic Rats

2021 ◽  
Vol 9 ◽  
Author(s):  
Ke Meng ◽  
Huabo Cai ◽  
Simin Cai ◽  
Yucai Hong ◽  
Xiaoming Zhang
Keyword(s):  
Myocardial Fibrosis ◽  
High Glucose ◽  
Cardiac Fibrosis ◽  
Therapeutic Potential ◽  
Heart Diseases ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
H9c2 Cells

Background: Accumulating evidence suggested that bone marrow mesenchymal stem cells (BMSCs) have therapeutic potential for diabetes and heart diseases. However, the effects of BMSC on reducing myocardial fibrosis need to be optimized. This study aimed to investigate the mechanism of adiponectin (APN) modified BMSCs on myocardial fibrosis in diabetic model in vivo and in vitro.Methods: The high-fat diet combined with streptozotocin (STZ) injection were used to induced diabetic rat model. H9c2 cells were cultured under a high glucose medium as in vitro model. The BMSCs were modified by APN plasmid or APN small interfering RNA (siRNA), then transplanted to the diabetic rats by a single tail-vein injection, or co-cultured with H9c2 cells.Results: We demonstrated that diabetic rats showed typical diabetic symptoms, such as decreased cardiac function, accumulation of pathological lesions and collagen expression. However, these impairments were significantly prevented by the APN modified BMSCs treatment while no effects on APN siRNA modified BMSCs treated diabetic rats. Moreover, we confirmed that APN modified BMSCs could attenuate the expression of TGF-beta1/smad to suppress the myocardial fibrosis in the diabetic rats and high glucose induced H9c2 cells.Conclusion: The present results for the first time showed that APN modified BMSCs exerted protection on cardiac fibrosis via inhibiting TGF-beta1/smad signal pathway in diabetic rats. Our findings suggested that APN modified BMSCs might be a novel and optimal therapy for the diabetic cardiomyopathy in future.

scholarly journals The Pattern of mRNA Expression Is Changed in Sinoatrial Node from Goto-Kakizaki Type 2 Diabetic Rat Heart

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
F. C. Howarth ◽  
M. A. Qureshi ◽  
P. Jayaprakash ◽  
K. Parekh ◽  
M. Oz ◽  
...  
Keyword(s):  
Heart Rate ◽  
Sinoatrial Node ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Cyclic Nucleotide Gated Channels ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Type 2 Diabetic

Background.In vivoexperiments in Goto-Kakizaki (GK) type 2 diabetic rats have demonstrated reductions in heart rate from a young age. The expression of genes encoding more than 70 proteins that are associated with the generation and conduction of electrical activity in the GK sinoatrial node (SAN) have been evaluated to further clarify the molecular basis of the low heart rate.Materials and Methods. Heart rate and expression of genes were evaluated with an extracellular electrode and real-time RT-PCR, respectively. Rats aged 12-13 months were employed in these experiments.Results. Isolated spontaneous heart rate was reduced in GK heart (161 ± 12 bpm) compared to controls (229 ± 11 bpm). There were many differences in expression of mRNA, and some of these differences were of particular interest. Compared to control SAN, expression of some genes were downregulated in GK-SAN: gap junction,Gja1(Cx43),Gja5(Cx40),Gjc1(Cx45), andGjd3(Cx31.9); cell membrane transport,Trpc1(TRPC1) and Trpc6 (TRPC6); hyperpolarization-activated cyclic nucleotide-gated channels,Hcn1(HCN1) andHcn4(HCN4); calcium channels,Cacna1d(Cav1.3),Cacna1g(Cav3.1),Cacna1h(Cav3.2),Cacna2d1(Cavα2δ1),Cacna2d3(Cavα2δ3), andCacng4(Cavγ4); and potassium channels,Kcna2(Kv1.2),Kcna4(Kv1.4),Kcna5(Kv1.5),Kcnb1 (Kv2.1),Kcnd3(Kv4.3),Kcnj2(Kir2.1),Kcnk1(TWIK1),Kcnk5(K2P5.1),Kcnk6(TWIK2), andKcnn2(SK2) whilst others were upregulated in GK-SAN:Ryr2(RYR2) andNppb(BNP).Conclusions. This study provides new insight into the changing expression of genes in the sinoatrial node of diabetic heart.

Insulin binding and glucose transport activity in cardiomyocytes of a diabetic rat

1986 ◽  
Vol 250 (4) ◽  
pp. E402-E406 ◽  
Author(s):  
E. C. Almira ◽  
A. R. Garcia ◽  
B. R. Boshell
Keyword(s):  
Glucose Transport ◽  
Insulin Binding ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Heart Cells ◽  
Apparent Difference ◽  
Insulin Effect ◽  
Streptozotocin Induced Diabetes

We studied insulin binding and glucose transport in isolated adult cardiomyocytes from rats with 2-wk streptozotocin-induced diabetes. At 37 degrees C, cells from diabetic rats bound less 125I-insulin and exhibited lower rates of 3-O-methylglucose transport than cells from control rats. In contrast, the amount of 125I-insulin bound to myocytes at 4 degrees C was the same in both groups. Preincubation of cells from both groups with 10-10,000 ng/ml insulin significantly increased their basal rates of glucose transport by approximately 40%. However, the augmented rates in diabetics were still approximately 36% lower than the corresponding insulin-stimulated rates in the controls. When the glucose transport data were expressed as percent maximal insulin effect and plotted as a function of the amount of insulin bound, the curves obtained from both diabetic and nondiabetic controls were superimposable. These data demonstrate that 1) heart cells from diabetic rats bind less insulin than from control rats under conditions in which they exhibit impaired glucose transport rates, 2) there is no apparent difference in total receptor number between the two groups, but internalization of intact insulin appears to be diminished in diabetes, 3) coupling exists between insulin binding and glucose transport in both groups, and 4) these impaired processes are completely reversed by insulin treatment in vivo but not in vitro.

scholarly journals Transplantation of photobiomodulation-preconditioned diabetic stem cells accelerates ischemic wound healing in diabetic rats

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Houssein Ahmadi ◽  
Abdollah Amini ◽  
Fatemeh Fadaei Fathabady ◽  
Atarodsadat Mostafavinia ◽  
Fatemeh Zare ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Function ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Closure Rate ◽  
Group 1

Abstract Background Diabetic foot ulcer is the most costly and complex challenge for patients with diabetes. We hereby assessed the effectiveness of different preconditioned adipose-derived mesenchymal stem cells (AD-MSCs) and photobiomodulation protocols on treating an infected ischemic wound in type 1 diabetic rats. Methods There were five groups of rats: (1) control, (2) control AD-MSCs [diabetic AD-MSCs were transplanted (grafted) into the wound bed], (3) AD-MSC + photobiomodulation in vivo (diabetic AD-MSCs were grafted into the wound, followed by in vivo PBM treatment), (4) AD-MSCs + photobiomodulation in vitro, and (5) AD-MSCs + photobiomodulation in vitro + in vivo. Results Diabetic AD-MSCs preconditioned with photobiomodulation had significantly risen cell function compared to diabetic AD-MSC. Groups 3 and 5 had significantly decreased microbial flora correlated to groups 1 and 2 (all, p = 0.000). Groups 2, 3, 4, and 5 had significantly improved wound closure rate (0.4, 0.4, 0.4, and 0.8, respectively) compared to group 1 (0.2). Groups 2–5 had significantly increased wound strength compared to group 1 (all p = 0.000). In most cases, group 5 had significantly better results than groups 2, 3, and 4. Conclusions Preconditioning diabetic AD-MSCs with photobiomodulation in vitro plus photobiomodulation in vivo significantly hastened healing in the diabetic rat model of an ischemic infected delayed healing wound.

scholarly journals Effects of kisspeptin on diabetic rat platelets

2017 ◽  
Vol 95 (11) ◽  
pp. 1319-1326 ◽  
Author(s):  
Zsófia Mezei ◽  
Sándor Váczi ◽  
Viktória Török ◽  
Csaba Stumpf ◽  
Rita Ónody ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Elevated Serum ◽  
Area Under The Curve ◽  
Diabetic Rats ◽  
Antagonistic Effect ◽  
The Body ◽  
Diabetic Rat ◽  
Animal Group

Hyperglycemia, hyperlipidemia, and free radicals result in platelet activation and atherogenesis. Kisspeptin (KP) is able to regulate metabolism, hemostasis, and the development of atherosclerosis. We examined whether platelet aggregation of streptozotocin-induced diabetic rats depends on the inducer type and if KP-13 and RF-9 (a kisspeptin receptor modifier) can influence platelet function. We measured the speed and the maximum of aggregation, along with the area under the curve. Serum glucose and calcium levels and urine formation of diabetic animals increased, while the body mass and platelet count decreased. Collagen was the most effective inducer of platelet aggregation. The aggregability of nondiabetic platelets was elevated in the presence of 5 × 10−8 mol/L KP-13. This effect was less expressed in diabetic animals. The effectivity of RF-9 was stronger than that of KP-13 in nondiabetic platelets, however it was ineffective in diabetic animals. RF-9 pre-treatment did not change the effects of 5 × 10−8 mol/L KP-13 in either animal group. The in vivo activation of diabetic platelets, which may be due to elevated serum calcium, induces thrombocytopenia and may lead to reduced in vitro aggregability. We could not demonstrate the antagonistic effect of RF-9 against KP-13 in isolated platelets.

scholarly journals Scutellarin Prevents Angiogenesis in Diabetic Retinopathy by Downregulating VEGF/ERK/FAK/Src Pathway Signaling

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Lingli Long ◽  
Yubin Li ◽  
Shuang Yu ◽  
Xiang Li ◽  
Yue Hu ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Oral Administration ◽  
Rat Model ◽  
Microvascular Dysfunction ◽  
Tube Formation ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Diabetic Rat Model

Background. Diabetic retinopathy (DR) is a serious microvascular complication of diabetes. This study demonstrates the antiangiogenic effects of scutellarin (SCU) on high glucose- and hypoxia-stimulated human retinal endothelial cells (HRECs) and on a diabetic rat model by oral administration. The antiangiogenic mechanisms of SCU in vitro and in vivo were investigated. Method. HRECs were cultured in high glucose- (30 mM D-glucose) and hypoxia (cobalt chloride-treated)-stimulated diabetic condition to evaluate the antiangiogenic effects of SCU by CCK-8 test, cell migration experiment (wound healing and transwell), and tube formation experiment. A streptozotocin-induced type II diabetic rat model was established to measure the effects of oral administration of SCU on protecting retinal microvascular dysfunction by Doppler waveforms and HE staining. We further used western blot, luciferase reporter assay, and immunofluorescence staining to study the antiangiogenic mechanism of SCU. The protein levels of phospho-ERK, phospho-FAK, phospho-Src, VEGF, and PEDF were examined in HRECs and retina of diabetic rats. Result. Our results indicated that SCU attenuated diabetes-induced HREC proliferation, migration, and tube formation and decreased neovascularization and resistive index in the retina of diabetic rats by oral administration. SCU suppressed the crosstalk of phospho-ERK, phospho-FAK, phospho-Src, and VEGF in vivo and in vitro. Conclusions. These results suggested that SCU can be an oral drug to alleviate microvascular dysfunction of DR and exerts its antiangiogenic effects by inhibiting the expression of the crosstalk of VEGF, p-ERK, p-FAK, and p-Src.

Roles of the subthalamic nucleus and subthalamic HCN channels in absence seizures

2012 ◽  
Vol 107 (1) ◽  
pp. 393-406 ◽  
Author(s):  
Daisuke Kase ◽  
Tsuyoshi Inoue ◽  
Keiji Imoto
Keyword(s):  
Basal Ganglia ◽  
Subthalamic Nucleus ◽  
Hcn Channels ◽  
Dependent Manner ◽  
Channel Activity ◽  
Hcn Channel ◽  
Membrane Excitability ◽  
Absence Seizures

Absence seizures consist of a brief and sudden impairment of consciousness. They are characterized by bilaterally synchronized spike and wave discharges (SWDs), which reflect abnormal oscillations in the thalamocortical loops. Recent studies have suggested that the basal ganglia are involved in generation of the SWDs, but their roles are poorly understood at the molecular and cellular levels. Here we studied the pathophysiological roles of the basal ganglia, using in vivo and in vitro measurements of tottering mice, a well-established model of absence epilepsy. We found that the membrane excitability in subthalamic nucleus (STN) neurons was enhanced in tottering mice, which resulted from reduced hyperpolarization-activated cyclic nucleotide-gated (HCN) channel activity. Pharmacological blockade and activation of HCN channel activity in vitro bidirectionally altered the membrane excitability of the STN neurons. Furthermore, these pharmacological modulations of HCN channel activity in the STN in vivo bidirectionally altered the mean SWD duration. In addition, STN deep brain stimulation modulated SWDs in a frequency-dependent manner. These results indicate that STN is involved in the rhythm maintenance system of absence seizures.

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