| Title |
Acute renal metabolic effect of metformin assessed with hyperpolarised MRI in rats
|
|---|---|
| Published in |
Diabetologia, September 2017
|
| DOI | 10.1007/s00125-017-4445-6 |
| Pubmed ID | |
| Authors |
Haiyun Qi, Per M. Nielsen, Marie Schroeder, Lotte B. Bertelsen, Fredrik Palm, Christoffer Laustsen |
| Abstract |
Metformin inhibits hepatic mitochondrial glycerol phosphate dehydrogenase, thereby increasing cytosolic lactate and suppressing gluconeogenesis flux in the liver. This inhibition alters cytosolic and mitochondrial reduction-oxidation (redox) potential, which has been reported to protect organ function in several disease states including diabetes. In this study, we investigated the acute metabolic and functional changes induced by metformin in the kidneys of both healthy and insulinopenic Wistar rats used as a model of diabetes. Diabetes was induced by intravenous injection of streptozotocin, and kidney metabolism in healthy and diabetic animals was investigated 4 weeks thereafter using hyperpolarised (13)C-MRI, Clark-type electrodes and biochemical analysis. Metformin increased renal blood flow, but did not change total kidney oxygen consumption. In healthy rat kidneys, metformin increased [1-(13)C]lactate production and reduced mitochondrial [1-(13)C]pyruvate oxidation (decreased the (13)C-bicarbonate/[1-(13)C]pyruvate ratio) within 30 min of administration. Corresponding alterations to indices of mitochondrial, cytosolic and whole-cell redox potential were observed. Pyruvate oxidation was maintained in the diabetic rats, suggesting that the diabetic state abrogates metabolic reprogramming caused by metformin. This study demonstrates that metformin-induced acute metabolic alterations in healthy kidneys favoured anaerobic metabolism at the expense of aerobic metabolism. The results suggest that metformin directly alters the renal redox state, with elevated renal cytosolic redox states as well as decreased mitochondrial redox state. These findings suggest redox biology as a novel target to eliminate the renal complications associated with metformin treatment in individuals with impaired renal function. |
X Demographics
The data shown below were collected from the profiles of 10 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Argentina | 1 | 10% |
| Japan | 1 | 10% |
| Germany | 1 | 10% |
| France | 1 | 10% |
| United States | 1 | 10% |
| United Kingdom | 1 | 10% |
| Unknown | 4 | 40% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 6 | 60% |
| Practitioners (doctors, other healthcare professionals) | 3 | 30% |
| Scientists | 1 | 10% |
Mendeley readers
The data shown below were compiled from readership statistics for 25 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 25 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 3 | 12% |
| Student > Master | 3 | 12% |
| Researcher | 3 | 12% |
| Student > Ph. D. Student | 2 | 8% |
| Professor > Associate Professor | 2 | 8% |
| Other | 3 | 12% |
| Unknown | 9 | 36% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 5 | 20% |
| Agricultural and Biological Sciences | 3 | 12% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 4% |
| Physics and Astronomy | 1 | 4% |
| Chemistry | 1 | 4% |
| Other | 0 | 0% |
| Unknown | 14 | 56% |
Attention Score in Context
This research output has an Altmetric Attention Score of 6. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 06 November 2018.
All research outputs
#5,666,292
of 23,015,156 outputs
Outputs from Diabetologia
#2,429
of 5,090 outputs
Outputs of similar age
#89,047
of 318,498 outputs
Outputs of similar age from Diabetologia
#71
of 85 outputs
Altmetric has tracked 23,015,156 research outputs across all sources so far. Compared to these this one has done well and is in the 75th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 5,090 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 22.7. This one has gotten more attention than average, scoring higher than 52% of its peers.
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We're also able to compare this research output to 85 others from the same source and published within six weeks on either side of this one. This one is in the 14th percentile – i.e., 14% of its contemporaries scored the same or lower than it.