A Low-Carbohydrate Diet Improves Glucose Metabolism in Lean Insulinopenic Akita Mice Along With Sodium-Glucose Cotransporter 2 Inhibitor
ObjectiveA low-carbohydrate diet (LC) can be beneficial to obese subjects with type2 diabetes mellitus (T2DM). Sodium-glucose cotransporter 2 inhibitor (SGLT2i) presents prompt glucose-lowering effects in subjects with T2DM. We investigated how LC and SGLT2i could similarly or differently influence...
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| Format: | Article |
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Frontiers Media S.A.
2020-12-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2020.601594/full |
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| author | Yukihiro Fujita Yukihiro Fujita Kuralay K. Atageldiyeva Kuralay K. Atageldiyeva Yasutaka Takeda Tsuyoshi Yanagimachi Tsuyoshi Yanagimachi Yuichi Makino Yuichi Makino Masakazu Haneda |
| author_facet | Yukihiro Fujita Yukihiro Fujita Kuralay K. Atageldiyeva Kuralay K. Atageldiyeva Yasutaka Takeda Tsuyoshi Yanagimachi Tsuyoshi Yanagimachi Yuichi Makino Yuichi Makino Masakazu Haneda |
| author_sort | Yukihiro Fujita |
| collection | DOAJ |
| description | ObjectiveA low-carbohydrate diet (LC) can be beneficial to obese subjects with type2 diabetes mellitus (T2DM). Sodium-glucose cotransporter 2 inhibitor (SGLT2i) presents prompt glucose-lowering effects in subjects with T2DM. We investigated how LC and SGLT2i could similarly or differently influence on the metabolic changes, including glucose, lipid, and ketone metabolism in lean insulinopenic Akita mice. We also examined the impacts of the combination.MethodsMale Akita mice were fed ad libitum normal-carbohydrate diet (NC) as a control or low-carbohydrate diet (LC) as an intervention for 8 weeks with or without SGLT2i treatment. Body weight and casual bold glucose levels were monitored during the study, in addition to measuring TG, NEFA, and ketone levels. We quantified gene expressions involved in gluconeogenesis, lipid metabolism and ketogenesis in the liver and the kidney. We also investigated the immunostaining analysis of pancreatic islets to assess the effect of islet protection.ResultsBoth LC and SGLT2i treatment reduced chronic hyperglycemia. Moreover, the combination therapy additionally ameliorated glycemic levels and preserved the islet morphology in part. LC but not SGLT2i increased body weight accompanied by epididymal fat accumulation. In contrast, SGLT2i, not LC potentiated four-fold ketone production with higher ketogenic gene expression, in comparison with the non-treated Akita mice. Besides, the combination did not enhance further ketone production compared to the SGLT2i alone.ConclusionsOur results indicated that both LC and SGLT2i reduced chronic hyperglycemia, and the combination presented synergistic favorable effects concomitantly with amelioration of islet morphology, while the combination did not enhance further ketosis in Akita mice. |
| first_indexed | 2024-12-16T11:04:52Z |
| format | Article |
| id | doaj.art-0390a136b35f49c588701e6adf104893 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-16T11:04:52Z |
| publishDate | 2020-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-0390a136b35f49c588701e6adf1048932022-12-21T22:33:52ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922020-12-011110.3389/fendo.2020.601594601594A Low-Carbohydrate Diet Improves Glucose Metabolism in Lean Insulinopenic Akita Mice Along With Sodium-Glucose Cotransporter 2 InhibitorYukihiro Fujita0Yukihiro Fujita1Kuralay K. Atageldiyeva2Kuralay K. Atageldiyeva3Yasutaka Takeda4Tsuyoshi Yanagimachi5Tsuyoshi Yanagimachi6Yuichi Makino7Yuichi Makino8Masakazu Haneda9Division of Metabolism and Biosystemic Science, Department of Internal Medicine, Asahikawa Medical University, Asahikawa, JapanDivision of Diabetology, Endocrinology and Nephrology, Department of Internal Medicine, Shiga University of Medical Science, Otsu, JapanDivision of Metabolism and Biosystemic Science, Department of Internal Medicine, Asahikawa Medical University, Asahikawa, JapanSchool of Medicine, Nazarbayev University, Nur-Sultan City, KazakhstanDivision of Metabolism and Biosystemic Science, Department of Internal Medicine, Asahikawa Medical University, Asahikawa, JapanDivision of Metabolism and Biosystemic Science, Department of Internal Medicine, Asahikawa Medical University, Asahikawa, JapanDivision of Diabetology, Endocrinology and Nephrology, Department of Internal Medicine, Shiga University of Medical Science, Otsu, JapanDivision of Metabolism and Biosystemic Science, Department of Internal Medicine, Asahikawa Medical University, Asahikawa, JapanIntegrated Medical Education Center, Asahikawa Medical University, Asahikawa, JapanDivision of Metabolism and Biosystemic Science, Department of Internal Medicine, Asahikawa Medical University, Asahikawa, JapanObjectiveA low-carbohydrate diet (LC) can be beneficial to obese subjects with type2 diabetes mellitus (T2DM). Sodium-glucose cotransporter 2 inhibitor (SGLT2i) presents prompt glucose-lowering effects in subjects with T2DM. We investigated how LC and SGLT2i could similarly or differently influence on the metabolic changes, including glucose, lipid, and ketone metabolism in lean insulinopenic Akita mice. We also examined the impacts of the combination.MethodsMale Akita mice were fed ad libitum normal-carbohydrate diet (NC) as a control or low-carbohydrate diet (LC) as an intervention for 8 weeks with or without SGLT2i treatment. Body weight and casual bold glucose levels were monitored during the study, in addition to measuring TG, NEFA, and ketone levels. We quantified gene expressions involved in gluconeogenesis, lipid metabolism and ketogenesis in the liver and the kidney. We also investigated the immunostaining analysis of pancreatic islets to assess the effect of islet protection.ResultsBoth LC and SGLT2i treatment reduced chronic hyperglycemia. Moreover, the combination therapy additionally ameliorated glycemic levels and preserved the islet morphology in part. LC but not SGLT2i increased body weight accompanied by epididymal fat accumulation. In contrast, SGLT2i, not LC potentiated four-fold ketone production with higher ketogenic gene expression, in comparison with the non-treated Akita mice. Besides, the combination did not enhance further ketone production compared to the SGLT2i alone.ConclusionsOur results indicated that both LC and SGLT2i reduced chronic hyperglycemia, and the combination presented synergistic favorable effects concomitantly with amelioration of islet morphology, while the combination did not enhance further ketosis in Akita mice.https://www.frontiersin.org/articles/10.3389/fendo.2020.601594/fulllow-carbohydrate dietsodium-glucose cotransporter 2 inhibitorketogenesisislet morphologyAkita mice |
| spellingShingle | Yukihiro Fujita Yukihiro Fujita Kuralay K. Atageldiyeva Kuralay K. Atageldiyeva Yasutaka Takeda Tsuyoshi Yanagimachi Tsuyoshi Yanagimachi Yuichi Makino Yuichi Makino Masakazu Haneda A Low-Carbohydrate Diet Improves Glucose Metabolism in Lean Insulinopenic Akita Mice Along With Sodium-Glucose Cotransporter 2 Inhibitor Frontiers in Endocrinology low-carbohydrate diet sodium-glucose cotransporter 2 inhibitor ketogenesis islet morphology Akita mice |
| title | A Low-Carbohydrate Diet Improves Glucose Metabolism in Lean Insulinopenic Akita Mice Along With Sodium-Glucose Cotransporter 2 Inhibitor |
| title_full | A Low-Carbohydrate Diet Improves Glucose Metabolism in Lean Insulinopenic Akita Mice Along With Sodium-Glucose Cotransporter 2 Inhibitor |
| title_fullStr | A Low-Carbohydrate Diet Improves Glucose Metabolism in Lean Insulinopenic Akita Mice Along With Sodium-Glucose Cotransporter 2 Inhibitor |
| title_full_unstemmed | A Low-Carbohydrate Diet Improves Glucose Metabolism in Lean Insulinopenic Akita Mice Along With Sodium-Glucose Cotransporter 2 Inhibitor |
| title_short | A Low-Carbohydrate Diet Improves Glucose Metabolism in Lean Insulinopenic Akita Mice Along With Sodium-Glucose Cotransporter 2 Inhibitor |
| title_sort | low carbohydrate diet improves glucose metabolism in lean insulinopenic akita mice along with sodium glucose cotransporter 2 inhibitor |
| topic | low-carbohydrate diet sodium-glucose cotransporter 2 inhibitor ketogenesis islet morphology Akita mice |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2020.601594/full |
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