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

Diabetes ◽  
2021 ◽  
pp. db201143
Author(s):  
Michael J. MacDonald ◽  
Israr-ul H. Ansari ◽  
Melissa J. Longacre ◽  
Scott W. Stoker
Keyword(s):  
Therapeutic Action ◽  
Glycerol Phosphate ◽  
Treatment Of Diabetes ◽  
Glycerol Phosphate Dehydrogenase

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.

Interferon inhibits the accumulation of glycerol phosphate dehydrogenase mRNA in oligodendrocytes and C6 cells

1989 ◽  
Vol 14 (10) ◽  
pp. 987-993 ◽  
Author(s):  
A. C. Passaquin ◽  
G. Coupin ◽  
W. A. Schreier ◽  
P. Poindron ◽  
R. A. Cole ◽  
...  
Keyword(s):  
C6 Cells ◽  
Glycerol Phosphate ◽  
Glycerol Phosphate Dehydrogenase
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