scholarly journals Metallothionein expression in slow- vs. fast-twitch muscle fibers following 4 weeks of streptozotocin-induced type 1 diabetes

FACETS ◽  
2018 ◽  
Vol 3 (1) ◽  
pp. 315-325 ◽  
Author(s):  
Pamela Mondragon ◽  
Andreas Bergdahl
Keyword(s):  
Oxidative Stress ◽  
Type 1 Diabetes ◽  
Molecular Mechanisms ◽  
Protein Carbonyl ◽  
Glucose Levels ◽  
Significant Difference ◽  
Streptozotocin Induced Diabetes ◽  
Carbonyl Formation ◽  
Fast Twitch

Type 1 diabetes (T1DM) is known to cause an increase in reactive oxygen species (ROS) and elevated intracellular glucose levels. We investigated the metallothionein I and II (MT I+II) antioxidants expression in soleus (mainly slow-twitch) and plantaris (predominantly fast-twitch) skeletal muscle using a rodent model of streptozotocin-induced diabetes. The presence of oxidative stress was confirmed by the detection of increased levels of protein carbonyl formation in the diabetic tissues. DAB (3,3′-diaminobenzidine) immunostaining and Western blotting analyses demonstrated that MT I+II expression was significantly upregulated in the diabetic soleus and plantaris muscle tissues compared with their respective controls. Moreover, no significant difference was detected between the plantaris and soleus controls or between the plantaris and soleus diabetic tissues. These findings suggest that there is an increase in MT protein expression in the soleus and plantaris muscles associated with the induction of T1DM. A better understanding of the molecular mechanisms that allow MT to prevent the oxidative stress associated with diabetes could lead to a novel therapeutic strategy for this chronic disease and its associated complications.

scholarly journals Comparing two treatment approaches for patients with type 1 diabetes during aerobic exercise: a randomised, crossover study

2020 ◽  
Author(s):  
Varun Vartak ◽  
Lynne Chepulis ◽  
Matt Driller ◽  
Ryan Paul
Keyword(s):  
Type 1 Diabetes ◽  
Blood Glucose ◽  
Aerobic Exercise ◽  
Blood Lactate ◽  
Perceived Exertion ◽  
Trial Registration ◽  
Glucose Levels ◽  
Significant Difference ◽  
Mild Hypoglycaemia

Abstract In a randomised, counterbalanced, crossover design, eight men with type 1 diabetes (T1D; mean ± SD age: 27.6 ± 11.4 years) reduced insulin (INS) by 50% of their normal dose or consumed carbohydrates equivalent to 1 g of carbohydrate/kg of their body weight without the usual insulin bolus (CARBS) over two sessions, held a week apart. Each session included standardised meals, a 45-minute treadmill-walk at 7.24 km.h-1 and a six-minute walk test (6MWT). Rate of perceived exertion (RPE), blood glucose, blood ketone and blood lactate measures were taken before, during and immediately after the aerobic exercise. The distance covered in metres and the predicted VO2 max (mL⋅kg−1⋅min−1) were also calculated for the 6MWT. Participants completing the INS intervention spent more time in normoglycaemia (242 ± 135 min vs 88 ± 132 min; P < 0.01) and less time in hyperglycaemia (41 ± 95 min vs 154 ± 125 min; P = 0.01) as compared to the CARBS intervention. Mild hypoglycaemia occurred in two participants during INS and no participants during CARBS. Furthermore, there was no significant difference for blood lactate, ketone, RPE, distance covered and predicted VO2 max between interventions. Based on this pilot study, INS intervention appears to be the best approach for maintaining blood glucose levels in those with T1D during aerobic exercise, though this does need evaluating in other groups, including women, children and those with sub-optimal glycaemic control. Trial registration: ACTRN12619001397101p. Registered 09 September 2019, http://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378264

Cellular and molecular mechanisms underlying immune tolerance against type 1 diabetes

2016 ◽  
Author(s):  
◽  
Weirong Chen
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Molecular Mechanisms ◽  
Antigen Presenting Cells ◽  
Insulin Dependent Diabetes Mellitus ◽  
The United States ◽  
Dependent Diabetes Mellitus ◽  
Glucose Levels ◽  
Antigen Presenting

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Type 1 diabetes (T1D), also known as insulin-dependent diabetes mellitus, is a chronic autoimmune disease caused by the destruction of insulin-producing beta-cells in the pancreatic islets by self-reactive immune cells. About three million Americans have T1D currently and each year there are more than 30,000 new T1D cases in the United States. Hyperglycemia in T1D patients may affect major organs and cause complications including cardiovascular diseases, nerve damage, kidney problems, blindness, and amputation. Unfortunately, there is no cure for T1D and T1D patients have to rely on life-long insulin replacement to maintain blood glucose levels in the normal range. Therefore, immunotherapies which target pathogenic T cells specifically while circumventing broad immune suppression are desired to treat T1D. Our lab has incorporated a mimotope p79 into an Ig molecule, and the resulting Ig-p79 chimera is able to prevent the adoptive transfer of T1D in NOD.scid mice by diabetogenic BDC2.5 T cells. Consequently, these T cells are retained in the spleen and cannot migrate to the pancreas due to diminished expression of the transcription factor T-bet and chemokine receptor CXCR3. Moreover, we found mTOR, a key serine/threonine protein kinase, is the major target of Ig-p79 and T cells undergoing antigen-induced tolerance have an impaired function of mTORC1, but not mTORC2. This mechanism is brought about by antigen presenting cells through upregulation of PD-L1 inhibitory molecules. Under this circumstance, PDL1 on antigen presenting cells interacts specifically with PD-1 on T cells, leading to recruitment of SHP-2 phosphatase to the cytoplasmic tail of PD-1. Active SHP-2 then induces dephosphorylation of phosphatidylinositol-3-kinase protein, which in turn results in the defective activity of mTORC1, diminished expression of CXCR3 and suppression of T1D development. Thus, our findings suggest that drugs that target mTORC1 in diabetogenic T cells would provide an approach to prevent and treat T1D. Moreover, this study also opens a new avenue for antigen presenting cells that express high levels of PD-L1 as means to induce tolerance of pathogenic T cells in T1D patients.

scholarly journals Comparing Two Treatment Approaches for Patients with Type 1 Diabetes During Aerobic Exercise: a Randomised, Crossover Study

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Varun Vartak ◽  
Lynne Chepulis ◽  
Matthew Driller ◽  
Ryan G. Paul
Keyword(s):  
Type 1 Diabetes ◽  
Blood Glucose ◽  
Aerobic Exercise ◽  
Perceived Exertion ◽  
Trial Registration ◽  
Clinical Trial Registry ◽  
Glucose Levels ◽  
Significant Difference ◽  
Mild Hypoglycaemia

Abstract Background In a randomised, counterbalanced, crossover design, eight men with type 1 diabetes (T1D; mean ± SD age, 27.6 ± 11.4 years) reduced insulin (INS) by 50% of their normal dose or consumed carbohydrates equivalent to 1 g of carbohydrate per kilogramme of their body weight without the usual insulin bolus (CARBS) over two sessions, held a week apart. Each session included standardised meals, a 45-min treadmill walk at 7.24 km h−1 and a 6-min walk test (6MWT). Rate of perceived exertion (RPE), blood glucose, ketone and lactate measures were taken before, during and immediately after the aerobic exercise. The distance covered in metres and the predicted VO2 max (mL kg−1 min−1) were also calculated for the 6MWT. Results Participants completing the INS intervention spent more time in normoglycaemia (242 ± 135 min vs 88 ± 132 min; P < 0.01) and less time in hyperglycaemia (41 ± 95 min vs 154 ± 125 min; P = 0.01) as compared to the CARBS intervention. Mild hypoglycaemia occurred in two participants during INS and no participants during CARBS. Furthermore, there was no significant difference for blood lactate, ketone, RPE, distance covered and predicted VO2 max between interventions. Conclusion Based on this pilot study, INS intervention appears to be the best approach for maintaining blood glucose levels in those with T1D during aerobic exercise, though this does need evaluation in other groups, including women, children and those with suboptimal glycaemic control. Trial Registration Australian New Zealand Clinical Trial Registry, ACTRN12619001397101p. Registered 09 September 2019.

scholarly journals Elucidation of Molecular Mechanisms of Streptozotocin-Induced Oxidative Stress, Apoptosis, and Mitochondrial Dysfunction in Rin-5F Pancreatic β-Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Arwa M. T. Al Nahdi ◽  
Annie John ◽  
Haider Raza
Keyword(s):  
Oxidative Stress ◽  
Type 1 Diabetes ◽  
Mitochondrial Dysfunction ◽  
Molecular Mechanisms ◽  
Pancreatic Beta Cell ◽  
Dependent Manner ◽  
Respiratory Enzymes ◽  
Altered Expression ◽  
Pancreatic Cancer Cells

Streptozotocin is a pancreatic beta-cell-specific cytotoxin and is widely used to induce experimental type 1 diabetes in rodent models. The precise molecular mechanism of STZ cytotoxicity is however not clear. Studies have suggested that STZ is preferably absorbed by insulin-secreting β-cells and induces cytotoxicity by producing reactive oxygen species/reactive nitrogen species (ROS/RNS). In the present study, we have investigated the mechanism of cytotoxicity of STZ in insulin-secreting pancreatic cancer cells (Rin-5F) at different doses and time intervals. Cell viability, apoptosis, oxidative stress, and mitochondrial bioenergetics were studied. Our results showed that STZ induces alterations in glutathione homeostasis and inhibited the activities of the respiratory enzymes, resulting in inhibition of ATP synthesis. Apoptosis was observed in a dose- and time-dependent manner. Western blot analysis has also confirmed altered expression of oxidative stress markers (e.g., NOS and Nrf2), cell signaling kinases, apoptotic protein-like caspase-3, PARP, and mitochondrial specific proteins. These results suggest that STZ-induced cytotoxicity in pancreatic cells is mediated by an increase in oxidative stress, alterations in cellular metabolism, and mitochondrial dysfunction. This study may be significant in better understanding the mechanism of STZ-induced β-cell toxicity/resistance and the etiology of type 1 diabetes induction.

scholarly journals Stem Cells in the Treatment of InsulinDependent Diabetes Mellitus

Acta Naturae ◽  
2016 ◽  
Vol 8 (3) ◽  
pp. 31-43 ◽  
Author(s):  
M. A. Borisov ◽  
O. S. Petrakova ◽  
I. G. Gvazava ◽  
E. N. Kalistratova ◽  
A. V. Vasiliev
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Blood Glucose ◽  
Molecular Mechanisms ◽  
Cellular Reprogramming ◽  
World Health ◽  
Autoimmune Reaction ◽  
Glucose Levels ◽  
Blood Glucose Levels

Diabetes affects over 350 million people worldwide, with the figure projected to rise to nearly 500 million over the next 20 years, according to the World Health Organization. Insulin-dependent diabetes mellitus (type 1 diabetes) is an endocrine disorder caused by an autoimmune reaction that destroys insulin-producing -cells in the pancreas, which leads to insulin deficiency. Administration of exogenous insulin remains at the moment the treatment mainstay. This approach helps to regulate blood glucose levels and significantly increases the life expectancy of patients. However, type 1 diabetes is accompanied by long-term complications associated with the systemic nature of the disease and metabolic abnormalities having a profound impact on health. Of greater impact would be a therapeutic approach which would overcome these limitations by better control of blood glucose levels and prevention of acute and chronic complications. The current efforts in the field of regenerative medicine are aimed at finding such an approach. In this review, we discuss the time-honored technique of donor islets of Langerhans transplantation. We also focus on the use of pluripotent stem and committed cells and cellular reprogramming. The molecular mechanisms of pancreatic differentiation are highlighted. Much attention is devoted to the methods of grafts delivery and to the materials used during its creation.

scholarly journals Comparing Two Treatment Approaches for Patients with Type 1 Diabetes During Aerobic Exercise: A Randomised, Crossover Study

2020 ◽  
Author(s):  
Varun Vartak ◽  
Lynne Chepulis ◽  
Matthew Driller ◽  
Ryan G. Paul
Keyword(s):  
Type 1 Diabetes ◽  
Blood Glucose ◽  
Aerobic Exercise ◽  
Blood Lactate ◽  
Perceived Exertion ◽  
Trial Registration ◽  
Glucose Levels ◽  
Significant Difference ◽  
Mild Hypoglycaemia

Abstract In a randomised, counterbalanced, crossover design, eight men with type 1 diabetes (T1D; mean ± SD age: 27.6 ± 11.4 years) reduced insulin (INS) or consumed carbohydrates without the usual insulin bolus (CARBS) over two sessions, held a week apart. Each session included standardised meals, a 45-minute treadmill-walk at 7.24 km.h-1 and a six-minute walk test (6MWT). Rate of perceived exertion (RPE), blood glucose, blood ketone and blood lactate measures were taken before, during and immediately after the aerobic exercise. The distance covered and the predicted VO2 max were also calculated for the 6MWT. Participants completing the INS intervention spent more time in normoglycaemia (P < 0.01) and less time in hyperglycaemia (P = 0.01) as compared to the CARBS intervention. Mild hypoglycaemia occurred in two participants during INS and no participants during CARBS. Furthermore, there was no significant difference for blood lactate, ketone, RPE, distance covered and predicted VO2 max between interventions. Six of the eight participants felt that their performance was better during INS, with all six (including the two participants that experienced mild hypoglycaemia) indicating that they would prefer to use this strategy for management of glycaemic during exercise in the future. Based on this pilot study, INS intervention appears to be the best approach for maintaining blood glucose levels in those with T1D during aerobic exercise, though this does need evaluating in other groups, including women, children and those with sub-optimal glycaemic control.Trial registration: ACTRN12619001397101p. Registered 09 September 2019, http://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378264

scholarly journals Physiological Characteristics of Type 1 Diabetes Patients during High Mountain Trekking

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Bartłomiej Matejko ◽  
Andrzej Gawrecki ◽  
Marta Wróbel ◽  
Jerzy Hohendorff ◽  
Teresa Benbenek-Klupa ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Insulin Dose ◽  
Time Frame ◽  
Physiological Characteristics ◽  
High Mountain ◽  
Good Glycemic Control ◽  
Glucose Levels ◽  
Daily Insulin Dose ◽  
Significant Difference

In this study, the aim was to provide observational data from an ascent to the summit of Mount Damavand (5670 meters above sea level (m.a.s.l), Iran) by a group of people with type 1 diabetes (T1DM), with a focus on their physiological characteristics. After a 3-day expedition, 18 T1DM patients, all treated with personal insulin pumps, successfully climbed Mount Damavand. Information was collected on their physiological and dietary behaviors, as well as medical parameters, such as carbohydrate consumption, glucose patterns, insulin dosing, and the number of hypo- and hyperglycemic episodes during this time frame. The participants consumed significantly less carbohydrates on day 3 compared to day 1 (16.4 vs. 23.1 carbohydrate units; p=0.037). Despite this, a gradual rise in the mean daily glucose concentration as measured with a glucometer was observed. Interestingly, the patients did not fully respond to higher insulin delivery as there was no significant difference in mean daily insulin dose during the expedition. There were more hyperglycemic episodes (≥180 mg/dL) per patient on day 3 vs. day 1 (p<0.05) and more severe hyperglycemic episodes (>250 mg/dL) per patient on days 2 (p<0.05) and 3 (p<0.05) vs. day 1. In summary, high mountain trekking is feasible for T1DM patients with good glycemic control and no chronic complications. However, some changes in dietary preferences and an observable rise in glucose levels may occur. This requires an adequate therapeutic response.

scholarly journals The Effects of Natural Clinoptilolite and Nano-Sized Clinoptilolite Supplementation on Glucose Levels and Oxidative Stress in Rats With Type 1 Diabetes

2018 ◽  
Vol 42 (1) ◽  
pp. 31-35 ◽  
Author(s):  
Behnoosh Hossein Nia ◽  
Sirous Khorram ◽  
Hassan Rezazadeh ◽  
Abdolrasol Safaiyan ◽  
Ali Tarighat-Esfanjani
Keyword(s):  
Oxidative Stress ◽  
Type 1 Diabetes ◽  
Glucose Levels ◽  
Natural Clinoptilolite ◽  
And Oxidative Stress
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