scholarly journals Metformin’s Therapeutic Action in the Treatment of Diabetes Does Not Involve Inhibition of Mitochondrial Glycerol Phosphate Dehydrogenase

2021 ◽  
Author(s):  
Michael J. MacDonald ◽  
Israr-ul H. Ansari ◽  
Melissa J. Longacre ◽  
Scott W. Stoker
Keyword(s):  
Adverse Effects ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Glycerol Phosphate ◽  
Beneficial Effects ◽  
Insulin Cells ◽  
Cast Doubt ◽  
Redox Shuttle ◽  
Treatment Of Diabetes ◽  
Glycerol Phosphate Dehydrogenase

Mitochondrial glycerol phosphate dehydrogenase (mGPD) is the rate-limiting enzyme of the glycerol phosphate redox shuttle. It was recently claimed that metformin, a first line drug used for the treatment of type 2 diabetes, inhibits liver mGPD 30-50% suppressing gluconeogenesis through a redox mechanism. Various factors cast doubt on this idea. Total body100% knockout of mGPD in mice has adverse effects in several tissues where mGPD is high, but has little or no effect in liver where mGPD is the lowest of ten tissues. Metformin has beneficial effects in humans in tissues with high levels of mGPD such as pancreatic beta cells where mGPD is much higher than in liver. Insulin secretion in mGPD knockout mouse beta cells is normal because, like liver, beta cells possess the malate aspartate redox shuttle that’s redox action is redundant to the glycerol phosphate shuttle. For these and other reasons we used four different enzyme assays to reassess whether metformin inhibited mGPD. Metformin did not inhibit mGPD in homogenates or mitochondria from insulin cells or liver cells. If metformin actually inhibited mGPD, adverse effects in tissues where the level of mGPD is much higher than in liver could prevent metformin’s use as a diabetes medicine.

scholarly journals Metformin’s Therapeutic Action in the Treatment of Diabetes Does Not Involve Inhibition of Mitochondrial Glycerol Phosphate Dehydrogenase

2021 ◽  
Author(s):  
Michael J. MacDonald ◽  
Israr-ul H. Ansari ◽  
Melissa J. Longacre ◽  
Scott W. Stoker
Keyword(s):  
Adverse Effects ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Glycerol Phosphate ◽  
Beneficial Effects ◽  
Insulin Cells ◽  
Cast Doubt ◽  
Redox Shuttle ◽  
Treatment Of Diabetes ◽  
Glycerol Phosphate Dehydrogenase

Mitochondrial glycerol phosphate dehydrogenase (mGPD) is the rate-limiting enzyme of the glycerol phosphate redox shuttle. It was recently claimed that metformin, a first line drug used for the treatment of type 2 diabetes, inhibits liver mGPD 30-50% suppressing gluconeogenesis through a redox mechanism. Various factors cast doubt on this idea. Total body100% knockout of mGPD in mice has adverse effects in several tissues where mGPD is high, but has little or no effect in liver where mGPD is the lowest of ten tissues. Metformin has beneficial effects in humans in tissues with high levels of mGPD such as pancreatic beta cells where mGPD is much higher than in liver. Insulin secretion in mGPD knockout mouse beta cells is normal because, like liver, beta cells possess the malate aspartate redox shuttle that’s redox action is redundant to the glycerol phosphate shuttle. For these and other reasons we used four different enzyme assays to reassess whether metformin inhibited mGPD. Metformin did not inhibit mGPD in homogenates or mitochondria from insulin cells or liver cells. If metformin actually inhibited mGPD, adverse effects in tissues where the level of mGPD is much higher than in liver could prevent metformin’s use as a diabetes medicine.

scholarly journals Metformin’s Therapeutic Action in the Treatment of Diabetes Does Not Involve Inhibition of Mitochondrial Glycerol Phosphate Dehydrogenase

2021 ◽  
Author(s):  
Michael J. MacDonald ◽  
Israr-ul H. Ansari ◽  
Melissa J. Longacre ◽  
Scott W. Stoker
Keyword(s):  
Adverse Effects ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Glycerol Phosphate ◽  
Beneficial Effects ◽  
Insulin Cells ◽  
Cast Doubt ◽  
Redox Shuttle ◽  
Treatment Of Diabetes ◽  
Glycerol Phosphate Dehydrogenase

Mitochondrial glycerol phosphate dehydrogenase (mGPD) is the rate-limiting enzyme of the glycerol phosphate redox shuttle. It was recently claimed that metformin, a first line drug used for the treatment of type 2 diabetes, inhibits liver mGPD 30-50% suppressing gluconeogenesis through a redox mechanism. Various factors cast doubt on this idea. Total body100% knockout of mGPD in mice has adverse effects in several tissues where mGPD is high, but has little or no effect in liver where mGPD is the lowest of ten tissues. Metformin has beneficial effects in humans in tissues with high levels of mGPD such as pancreatic beta cells where mGPD is much higher than in liver. Insulin secretion in mGPD knockout mouse beta cells is normal because, like liver, beta cells possess the malate aspartate redox shuttle that’s redox action is redundant to the glycerol phosphate shuttle. For these and other reasons we used four different enzyme assays to reassess whether metformin inhibited mGPD. Metformin did not inhibit mGPD in homogenates or mitochondria from insulin cells or liver cells. If metformin actually inhibited mGPD, adverse effects in tissues where the level of mGPD is much higher than in liver could prevent metformin’s use as a diabetes medicine.

scholarly journals Salvia Officinalis Protects Pancreatic Beta-cells Against Streptozotocin-Induced Damage; A Stereological Study

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Soheil Ashkani-Esfahani ◽  
Ali Noorafshan ◽  
Alireza Ebrahimi ◽  
Maryam Bahmani-Jahromi ◽  
Mohammad-Hossein Imanieh ◽  
...  
Keyword(s):  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Pancreatic Injury ◽  
Food Supplement ◽  
Salvia Officinalis ◽  
Diabetic Group ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Beneficial Effects ◽  
Patients With Diabetes

Background: Diabetes mellitus (DM) is a chronic disease, progressing due to inadequate secretion of insulin by pancreas. Salvia officinalis (SVO) has anti-inflammatory and anti-oxidative potentials, which may be beneficial in regulating underlying causes of DM. Objectives: In this study, we aimed to estimate the protective effects of SVO against Streptozotocin (STZ)-induced pancreatic injury in rat models of DM. Methods: Forty-eight male Sprague-Dawley rats were randomly divided into four groups (n = 12); C1: normal group with no treatment, C2: diabetic group with no treatment, E1: diabetic group treated with 200 mg/kg of the SVO extract, and E2: diabetic group treated with 400 mg/kg of the SVO extract. All groups received a single dose of STZ on day 7 except C1. Pancreas volume, shrinkage, volume densities of the islets, numerical densities, and volume of the beta cells were measured using stereological methods. Results: Blood sugar (BS) levels were significantly lower in SVO-treated groups comparing to C2 group. Also, volume densities and total number of islets and beta cells in E1 and E2 groups were higher than C2 (P < 0.05), but lower than C1 (P < 0.05). Volume densities of the islets and beta cells, and total number of beta cells in E1, and volume densities of the islets and beta cells in E2 groups were considerably higher than C2 group (P < 0.05). Conclusions: Our result showed the beneficial effects of SVO extract regarding pancreatic damage. We concluded that SVO might be prescribed as a therapeutic food supplement for patients with diabetes.

scholarly journals Effects of physical exercise on beta cells of the pancreas: a systematic review

2020 ◽  
pp. 1-6
Author(s):  
Edson Meneses da Silva Filho ◽  
Jéssica Andrade de Albuquerque ◽  
Roberta de Oliveira Cacho ◽  
Rodrigo Pegado de Abreu Freitas
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Physical Exercise ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Randomized Clinical Trials ◽  
Qualitative Evaluation ◽  
Cochrane Collaboration ◽  
Cochrane Library ◽  
Beneficial Effects

Background: Diabetes mellitus is a chronic disease that is rising in many parts of the world causing damage to functionality, quality of life and public health system. Objective: Verify the effects of physical exercise on beta cells of the pancreas in diabetic subjects. Methods: The database Cochrane Library via Wiley – CENTRAL, Pubmed, LILACS, SCIELO, Web of Science, Scopus, CINAHL were used to search the articles. The descriptors and synonyms of this topic were used in the search strategy. Controlled randomized clinical trials and quasi-randomized studies, which included in their samples diabetic humans undergone any type of physical exercise were included. The Cochrane collaboration bias risk tool was used to assess the risk of bias. Results: A total of 3.133 articles were initially identified and after reading the titles/abstracts and the full text 6 articles were selected for the qualitative evaluation. Most of the studies showed positive results of physical exercise on pancreatic beta cells, insulin secretion, insulin resistance and insulin sensitivity. The main limitations were the number of studies, few, and their methodological qualities. Conclusions: Physical exercises have beneficial effects on pancreatic beta cells, insulin resistance and insulin sensitivity; however better studies designs, with fewer biases and larger samples are needed so that the results presented do not be overestimated. This review is recorded in the Prospective Register of Systematic Reviews with registration number 42017054213

Beneficial effects of antioxidants in diabetes: possible protection of pancreatic beta-cells against glucose toxicity

Diabetes ◽  
1999 ◽  
Vol 48 (12) ◽  
pp. 2398-2406 ◽  
Author(s):  
H. Kaneto ◽  
Y. Kajimoto ◽  
J. Miyagawa ◽  
T. Matsuoka ◽  
Y. Fujitani ◽  
...  
Keyword(s):  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Glucose Toxicity ◽  
Beneficial Effects

scholarly journals Stem Cell Therapy for Diabetes: Beta Cells versus Pancreatic Progenitors

2020 ◽  
Author(s):  
Essam Abdelalim ◽  
Bushra Memon
Keyword(s):  
Cell Therapy ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
High Blood Glucose ◽  
Pancreatic Progenitors ◽  
Treatment Of Diabetes ◽  
Cell Subpopulations ◽  
Glucose Responsiveness

Diabetes mellitus (DM) is one of the most prevalent metabolic disorders. In order to replace the function of the destroyed pancreatic beta cells in diabetes, islet transplantation is the widely practiced treatment; however, it has several limitations. As an alternative approach, human pluripotent stem cells (hPSCs) can provide an unlimited source of pancreatic cells that have the ability to secrete insulin in response to high blood glucose level. However, determination of the appropriate pancreatic lineage candidate for the purpose of cell therapy for treatment of diabetes is still debated upon. While hPSC-derived beta cells are perceived as the ultimate candidate, the efficiency needs further improvement in order to obtain a sufficient number of glucose responsive &beta;-cells for transplantation therapy. On the other hand, hPSC-derived pancreatic progenitors can be efficiently generated in vitro and can further mature into glucose responsive beta cells in vivo after transplantation. Herein, we discuss the advantages and predicted challenges associated with the use of each of the two pancreatic lineage products for diabetes cell therapy. Furthermore, we address co-generation of functionally relevant islet cell subpopulations and structural properties contributing to glucose responsiveness of beta cells, as well as the available encapsulation technology for these cells.

scholarly journals If Metformin Inhibited the Mitochondrial Glycerol Phosphate Dehydrogenase It Might Not Benefit Diabetes

2020 ◽  
Author(s):  
Michael J. MacDonald ◽  
Israr-ul H. Ansari ◽  
Melissa J. Longacre ◽  
Scott W. Stoker
Keyword(s):  
Insulin Secretion ◽  
Liver Cells ◽  
Glycerol Phosphate ◽  
Insulin Cells ◽  
Total Body ◽  
Rate Limiting ◽  
Line Drug ◽  
Glycerol Phosphate Dehydrogenase ◽  
Inhibit Insulin Secretion

The mitochondrial glycerol phosphate dehydrogenase is the rate-limiting enzyme of the glycerol phosphate shuttle. It was recently claimed that metformin, a first line drug used worldwide for the treatment of type 2 diabetes, works by inhibiting the mitochondrial glycerol phosphate dehydrogenase 30-50% thus suppressing hepatic gluconeogenesis. This enzyme is 30-60 fold higher in the pancreatic islet than in liver. If metformin actually inhibited the enzyme, why would it not inhibit insulin secretion and exacerbate diabetes? Total body knockout of the mitochondrial glycerol phosphate dehydrogenase does not inhibit insulin secretion because insulin cells and liver cells possess the malate aspartate shuttle that is redundant to the action of the glycerol phosphate shuttle. In view of these and other apparent inconsistencies we reassessed the idea that metformin inhibited the mitochondrial glycerol phosphate dehydrogenase. We measured the enzyme’s activity in whole cell homogenates and mitochondria of insulin cells and liver cells using four different enzyme assays and were unable to show that metformin directly inhibits the enzyme. We conclude that metformin does not actually inhibit the enzyme. If it did, it might not be efficacious as a diabetes medicine.

scholarly journals Stem Cell Therapy for Diabetes: Beta Cells versus Pancreatic Progenitors

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 283 ◽  
Author(s):  
Bushra Memon ◽  
Essam M. Abdelalim
Keyword(s):  
Cell Therapy ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
High Blood Glucose ◽  
Pancreatic Progenitors ◽  
Treatment Of Diabetes ◽  
Cell Subpopulations ◽  
Glucose Responsiveness

Diabetes mellitus (DM) is one of the most prevalent metabolic disorders. In order to replace the function of the destroyed pancreatic beta cells in diabetes, islet transplantation is the most widely practiced treatment. However, it has several limitations. As an alternative approach, human pluripotent stem cells (hPSCs) can provide an unlimited source of pancreatic cells that have the ability to secrete insulin in response to a high blood glucose level. However, the determination of the appropriate pancreatic lineage candidate for the purpose of cell therapy for the treatment of diabetes is still debated. While hPSC-derived beta cells are perceived as the ultimate candidate, their efficiency needs further improvement in order to obtain a sufficient number of glucose responsive beta cells for transplantation therapy. On the other hand, hPSC-derived pancreatic progenitors can be efficiently generated in vitro and can further mature into glucose responsive beta cells in vivo after transplantation. Herein, we discuss the advantages and predicted challenges associated with the use of each of the two pancreatic lineage products for diabetes cell therapy. Furthermore, we address the co-generation of functionally relevant islet cell subpopulations and structural properties contributing to the glucose responsiveness of beta cells, as well as the available encapsulation technology for these cells.

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