Type I diabetes suppresses intracellular calcium ion increase normally evoked by heat stress in rat skeletal muscle

2021 ◽  
Author(s):  
Ryo Ikegami ◽  
Hiroaki Eshima ◽  
Toshiaki Nakajima ◽  
Shigeru Toyoda ◽  
David C. Poole ◽  
...  
Keyword(s):  
Heat Stress ◽  
Protein Expression ◽  
Type I Diabetes ◽  
Diabetic Rats ◽  
Diabetic Patients ◽  
Type I ◽  
Male Wistar Rats ◽  
Intracellular Calcium Ion ◽  
And Function

Heat stress, via its effects on muscle intracellular Ca2+ concentrations ([Ca2+]i), has been invoked as a putative therapeutic countermeasure to Type 1 diabetes-induced muscle atrophy. Using in vivo muscle preparation we tested the hypothesis that impaired muscle Ca2+ homeostasis in type I diabetic rats is due to attenuated heat stress tolerance mediated via TRPV1. Male Wistar rats were assigned to 1 of 4 groups: 1.control 30oC (CONT 30oC), 2.CONT 40oC, 3.diabetes 30oC (DIA 30oC), 4.DIA 40oC. 40oC was selected because it just exceeds the TRPV1 activation threshold. Spinotrapezius muscles were exteriorized in vivo and loaded with the fluorescent Ca2+ probe Fura-2AM. [Ca2+]i was estimated over 20min using fluorescence microscopy in quiescent muscle held at the required temperature using calibrated heat source applied to the ventral muscle surface. Western blotting was performed to determine the protein expression levels of TRPV1 in spinotrapezius muscle. After 20min of heat stress, the CONT 40oC condition induced a 12.3% [Ca2+]i elevation that was absent from the DIA 40oC or other conditions. Thus, no significant differences were found among DIA 40oC, DIA 30oC and CONT 30oC. TRPV1 protein expression was decreased by 42.0% in DIA compared with CONT (P<0.05) and, unlike CONT, heat stress did not increase TRPV1 phosphorylation. In conclusion, diabetes suppresses TRPV1 protein expression and function and inhibits the elevated myocyte [Ca2+]i evoked normally by heat stress. These results suggest that capsaicin or other therapeutic strategies to increase Ca2+ accumulation via TRPV1 might be more effective than hyperthermic therapy for Type I diabetic patients.

scholarly journals Angiotensin II-NADPH oxidase-derived superoxide mediates diabetes-attenuated cell excitability of aortic baroreceptor neurons

2011 ◽  
Vol 301 (6) ◽  
pp. C1368-C1377 ◽  
Author(s):  
Yu-Long Li ◽  
Hong Zheng
Keyword(s):  
Angiotensin Ii ◽  
Nadph Oxidase ◽  
Protein Expression ◽  
Current Density ◽  
Diabetic Rats ◽  
Diabetic Patients ◽  
Type I ◽  
Patch Clamp Technique ◽  
Cell Excitability ◽  
Nodose Ganglia

Overactivation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels is involved in diabetes-depressed excitability of aortic baroreceptor neurons in nodose ganglia. This involvement links to the autonomic dysfunction associated with high morbidity and mortality in diabetic patients. The present study examined the effects of an angiotensin II type I receptor (AT1R) antagonist (losartan), a NADPH oxidase inhibitor (apocynin), and a superoxide dismutase mimetic (tempol) on the enhanced HCN currents and attenuated cell excitability in diabetic nodose neurons. In sham and streptozotocin-induced type 1 diabetic rats, HCN currents and cell excitability of aortic baroreceptor neurons were recorded by the whole cell patch-clamp technique. The angiotensin II level in nodose ganglia from diabetic rats was higher than that from sham rats (101.6 ± 4.8 vs. 38.9 ± 4.2 pg/mg protein, P < 0.05). Single-cell RT-PCR, Western blot, immunofluorescence staining, and chemiluminescence data showed that mRNA and protein expression of AT1R, protein expression of NADPH oxidase components, and superoxide production in nodose neurons were increased in diabetic rats compared with those from sham rats. HCN current density was higher and cell excitability was lower in aortic baroreceptor neurons from diabetic rats than that from sham rats. Losartan (1 μM), apocynin (100 μM), and tempol (1 mM) normalized the enhanced HCN current density and increased the cell excitability in the aortic baroreceptor neurons of diabetic rats. These findings suggest that endogenous angiotensin II-NADPH oxidase-superoxide signaling contributes to the enhanced HCN currents and the depressed cell excitation in the aortic baroreceptor neurons of diabetic rats.

Enhancement of Spontaneous Fibrinolytic Activity in Diabetic Retinopathy

1992 ◽  
Vol 68 (04) ◽  
pp. 400-403 ◽  
Author(s):  
Helmut Ostermann ◽  
Diethelm Tschöpe ◽  
Wolfgang Greber ◽  
Hans-Werner Meyer-Rüsenberg ◽  
Jürgen van de Loo
Keyword(s):  
Fibrinolytic Activity ◽  
Type I Diabetes ◽  
Plasminogen Activator Inhibitor ◽  
Venous Occlusion ◽  
Fibrinolytic System ◽  
Clot Lysis ◽  
Diabetic Patients ◽  
Type I ◽  
Activated State

SummaryThe fibrinolytic system was studied in 96 patients with type I diabetes mellitus. Patients were grouped according to their degree of retinopathy; 38 patients with no evidence of retinopathy, 28 patients with background retinopathy and 30 patients with proliferative retinopathy. Thirty healthy individuals served as controls. The basal fibrinolytic activity as measured by clot lysis time and t-PA activity was increased in diabetic patients. This was associated with low levels of plasminogen activator inhibitor. Increased levels of D-dimer in diabetic patients further indicate enhanced in vivo fibrinolysis. The increase in fibrinolytic activity was highest in diabetics without retinopathy, and decreased with increasing retinopathy. Endothelial release of t-PA after venous occlusion was not different between controls and all diabetic groups. These findings suggest that in type I diabetics the fibrinolytic system is in an activated state. With worsening of retinopathy this increase in fibrinolytic activity diminishes.

scholarly journals In Vivo Imaging of Pancreatic Islet Grafts in Diabetes Treatment

2021 ◽  
Vol 12 ◽  
Author(s):  
Dian R. Arifin ◽  
Jeff W. M. Bulte
Keyword(s):  
Type I Diabetes ◽  
Type I ◽  
Related Factors ◽  
Non Invasive ◽  
Underlying Causes ◽  
The Many ◽  
And Function ◽  
Glucose Management ◽  
Invasive Techniques

Transplantation of pancreatic islets has potential to offer life-long blood glucose management in type I diabetes and severe type II diabetes without the need of exogenous insulin administration. However, islet cell therapy suffers from autoimmune and allogeneic rejection as well as non-immune related factors. Non-invasive techniques to monitor and evaluate the fate of cell implants in vivo are essential to understand the underlying causes of graft failure, and hence to improve the precision and efficacy of islet therapy. This review describes how imaging technology has been employed to interrogate the distribution, number or volume, viability, and function of islet implants in vivo. To date, fluorescence imaging, PET, SPECT, BLI, MRI, MPI, and ultrasonography are the many imaging modalities being developed to fulfill this endeavor. We outline here the advantages, limitations, and clinical utility of each particular imaging approach.

scholarly journals Multidisciplinary Foot Clinics Impact on the Diabetic World

2015 ◽  
Vol 8 (3) ◽  
Author(s):  
Chavan Williams
Keyword(s):  
Type I Diabetes ◽  
The Body ◽  
Lower Limbs ◽  
Diabetic Patients ◽  
Type I ◽  
Type Ii ◽  
Foot Complications ◽  
After Care ◽  
Health Complications ◽  
And Function

In today’s society, diabetes is a prevalent illness afflicting people of various races, ages, genders and social statuses(1). Diabetes is a chronic illness in which the body is unable to break down sugars due to poor insulin production and function(3). Diabetes can be classified as type I or as type II, and may be categorized as moderate or advanced. In type I diabetes, a person isn’t able to produce insulin, while someone with type II diabetes cannot produce enough insulin and suffers from “insulin resistance”(3). Diabetic patients may suffer from health complications as the illness becomes more advanced, such as foot complications. Often, foot complications can result in amputation of the lower limbs or in some cases, mortality. To address this problem, multidisciplinary foot clinics have been created to aid patients, reduce mortality rates, and decrease the occurrence of limb amputations. These programs provide information to diabetic patients and their families, providing foot-oriented treatments and monitoring patients’ progress through after care. This article will argue that the practices and procedures in multidisciplinary foot clinics help significantly reduce diabetic foot complications, resulting in amputation or death for diabetic patients.

Platelet Factor 4, β-Thromboglobulin and Thrombospondin Levels in Type I Diabetes Mellitus Patients

1994 ◽  
Vol 22 (2) ◽  
pp. 90-94 ◽  
Author(s):  
M Bayraktar ◽  
S Dündar ◽  
S Kirazli ◽  
F Teletar
Keyword(s):  
Diabetes Mellitus ◽  
Type I Diabetes ◽  
Platelet Factor 4 ◽  
Type I Diabetes Mellitus ◽  
Control Group ◽  
Diabetic Patients ◽  
Type I ◽  
Platelet Factor ◽  
Release Reaction

The proteins β-thromboglobulin, platelet factor 4 and thrombospondin are stored in platelet α-granules and released from the platelet by the release reaction. The assays of these proteins were studied in patients with type I diabetes mellitus ( n = 30) and a healthy control group ( n = 15). Platelet factor 4 and β-thromboglobulin levels were not significantly different in both groups but thrombospondin concentrations in diabetic patients were significantly higher than those of the control group (136.6 ± 14.2 ng/ml vs 91.2 ± 14.3 ng/ml, P < 0.05). When the diabetic patients were divided into those with or without complications, the diabetic patients with complications ( n = 11) had significantly elevated plasma thrombospondin concentrations compared with the control group (150.4 ± 23.7 ng/ml vs 91.2 ± 14.3 ng/ml, P < 0.05), while thrombospondin concentrations in the control group were not statistically different from the diabetic patients without complications. Plasma β-thromboglobulin and platelet factor 4 levels were not significantly different between the diabetic and the control group. It is suggested that thrombospondin may be a convenient marker of in vivo platelet release reaction.

Stem Cell-Based Therapies: A New Ray of Hope for Diabetic Patients

2019 ◽  
Vol 14 (2) ◽  
pp. 146-151 ◽  
Author(s):  
Junaid Khan ◽  
Amit Alexander ◽  
Mukta Agrawal ◽  
Ajazuddin ◽  
Sunil Kumar Dubey ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Drug Therapy ◽  
Type I Diabetes ◽  
Embryonic Stem ◽  
Health Concern ◽  
Future Research ◽  
Diabetic Patients ◽  
Successful Implementation ◽  
Type I

Diabetes and its complications are a significant health concern throughout the globe. There are physiological differences in the mechanism of type-I and type-II diabetes and the conventional drug therapy as well as insulin administration seem to be insufficient to address the problem at large successfully. Hypoglycemic swings, frequent dose adjustments and resistance to the drug are major problems associated with drug therapy. Cellular approaches through stem cell based therapeutic interventions offer a promising solution to the problem. The need for pancreatic transplants in case of Type- I diabetes can also be by-passed/reduced due to the formation of insulin producing β cells via stem cells. Embryonic Stem Cells (ESCs) and induced Pluripotent Stem Cells (iPSCs), successfully used for generating insulin producing &#946; cells. Although many experiments have shown promising results with stem cells in vitro, their clinical testing still needs more exploration. The review attempts to bring into light the clinical studies favoring the transplantation of stem cells in diabetic patients with an objective of improving insulin secretion and improving degeneration of different tissues in response to diabetes. It also focuses on the problems associated with successful implementation of the technique and possible directions for future research.

A program to reduce onset distress in unselected type I diabetic patients: effects on psychological variables and metabolic control

1995 ◽  
Vol 132 (5) ◽  
pp. 580-586 ◽  
Author(s):  
K Spiess ◽  
G Sachs ◽  
P Pietschmann ◽  
R Prager
Keyword(s):  
Patient Education ◽  
Metabolic Control ◽  
Type I Diabetes ◽  
Intensive Treatment ◽  
Medical Psychology ◽  
Diabetic Patients ◽  
Type I ◽  
Psychological Variables ◽  
Reduction Program

Spiess K, Sachs G, Pietschmann P, Prager R. A program to reduce onset distress in unselected type I diabetic patients: effects on psychological variables and metabolic control. Eur J Endocrinol 1995;132:580–6. ISSN 0804–4643 This paper reports the results of a prospective controlled trial of a program addressing reduction of onset distress and better future adaptation in adults who were enrolled at the time of diagnosis of type I diabetes mellitus. Patients were assigned randomly to either standard intensive treatment and patient education with the distress reduction program (N = 10) or to standard intensive treatment and patient education without this program (N = 13). Prospective follow-up of patients with multiple validated measures of treatment outcome showed less anxious coping behavior, less depression and less denial at the 9-month follow-up and less denial at the 15-month follow-up in the group with the distress reduction program, but no differences in metabolic control between the two groups at any time. We conclude that our program has a positive impact on the crisis at diabetes onset; the lower denial in the treatment group may lead to improved regimen adherence in the long term. Klaus Spiess, Institute of Medical Psychology, University of Vienna, Severingasse 9, A-1090-Vienna, Austria

Isoform-specific expression and function of neuregulin

Development ◽  
1997 ◽  
Vol 124 (18) ◽  
pp. 3575-3586 ◽  
Author(s):  
D. Meyer ◽  
T. Yamaai ◽  
A. Garratt ◽  
E. Riethmacher-Sonnenberg ◽  
D. Kane ◽  
...  
Keyword(s):  
Biological Effects ◽  
Type I ◽  
Mouse Development ◽  
Specific Expression ◽  
Independent Functions ◽  
Cell Growth And Differentiation ◽  
Cranial Ganglia ◽  
And Function

Neuregulin (also known as NDF, heregulin, ARIA, GGF or SMDF), induces cell growth and differentiation. Biological effects of neuregulin are mediated by members of the erbB family of tyrosine kinase receptors. Three major neuregulin isoforms are produced from the gene, which differ substantially in sequence and in overall structure. Here we use in situ hybridization with isoform-specific probes to illustrate the spatially distinct patterns of expression of the isoforms during mouse development. Ablation of the neuregulin gene in the mouse has demonstrated multiple and independent functions of this factor in development of both the nervous system and the heart. We show here that targeted mutations that affect different isoforms result in distinct phenotypes, demonstrating that isoforms can take over specific functions in vivo. Type I neuregulin is required for generation of neural crest-derived neurons in cranial ganglia and for trabeculation of the heart ventricle, whereas type III neuregulin plays an important role in the early development of Schwann cells. The complexity of neuregulin functions in development is therefore due to independent roles played by distinct isoforms.

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