Mechanism of fat-induced hepatic gluconeogenesis: effect of metformin
| Autor: | Sofianos Andrikopoulos, Anne W. Thorburn, Joseph Proietto, Shaoming Song, Christine Filippis, David Khan |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty Physiology Endocrinology Diabetes and Metabolism medicine.medical_treatment Fructose 1 6-bisphosphatase Administration Oral Fatty Acids Nonesterified chemistry.chemical_compound Insulin resistance Physiology (medical) Diabetes mellitus Internal medicine medicine Animals Hypoglycemic Agents Insulin Rats Wistar Alanine biology Glycogen Body Weight Gluconeogenesis medicine.disease Dietary Fats Metformin Fructose-Bisphosphatase Rats Glucose Endocrinology Liver chemistry Glucose-6-Phosphatase biology.protein Phosphoenolpyruvate Carboxykinase (GTP) Glucose 6-phosphatase medicine.drug |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 281:E275-E282 |
| ISSN: | 1522-1555 0193-1849 |
| DOI: | 10.1152/ajpendo.2001.281.2.e275 |
| Popis: | High-fat feeding has been shown to cause hepatic insulin resistance. The aims of this study were to investigate the biochemical steps responsible for enhanced gluconeogenesis as a result of increased dietary fat intake and the site or sites at which the antihyperglycemic agent metformin acts to inhibit this process. Male Hooded Wistar rats were fed either a standard chow diet (5% fat by weight) or a high-fat diet (60% fat by weight) for 14 days with or without metformin. Total endogenous glucose production and gluconeogenesis were determined using [6-3H]glucose and [U-14C]alanine, respectively. Gluconeogenic enzyme activity and, where appropriate, protein and mRNA levels were measured in liver tissues. The high-fat diet increased endogenous glucose production (21.9 ± 4.4 vs. 32.2 ± 4.8 μmol · kg−1· min−1, P < 0.05) and alanine gluconeogenesis (4.5 ± 0.9 vs. 9.6 ± 1.9 μmol · kg−1· min−1, P < 0.05). Metformin reduced both endogenous glucose production (32.2 ± 4.8 vs. 16.1 ± 2.1 μmol · kg−1· min−1, P < 0.05) and alanine gluconeogenesis (9.6 ± 1.9 vs. 4.7 ± 0.8 μmol · kg−1· min−1, P < 0.05) after high-fat feeding. These changes were reflected in liver fructose-1,6-bisphosphatase protein levels (4.5 ± 0.9 vs. 9.6 ± 1.9 arbitrary units, P < 0.05 chow vs. high-fat feeding; 9.5 ± 1.9 vs. 4.7 ± 0.8 arbitrary units, P < 0.05 high fat fed in the absence vs. presence of metformin) but not in changes to the activity of other gluconeogenic enzymes. There was a significant positive correlation between alanine gluconeogenesis and fructose-1,6-bisphosphatase protein levels ( r = 0.56, P < 0.05). Therefore, excess supply of dietary fat stimulates alanine gluconeogenesis via an increase in fructose-1,6-bisphosphatase protein levels. Metformin predominantly inhibits alanine gluconeogenesis by preventing the fat-induced changes in fructose-1,6-bisphosphatase levels. |
| Databáze: | OpenAIRE |
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