Contributions of Hepatic Gluconeogenesis Suppression and Compensative Glycogenolysis on the Glucose-Lowering Effect of CS-917, a Fructose 1,6-Bisphosphatase Inhibitor, in Non-obese Type 2 Diabetes Goto-Kakizaki Rats

Yoshida, Takatoshi; Okuno, Akira; Takahashi, Kanako; Ogawa, Jun; Hagisawa, Yuka; Kanda, Shoichi; Fujiwara, Toshihiko

doi:10.1254/jphs.10262fp

Cited by 8 publications

(4 citation statements)

References 23 publications

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“…Together with PEPCK and G6Pase overexpression, these changes in FBPase subcellular distribution could explain the elevated gluconeogenic activity observed during fasting and diabetes. A specific FBPase inhibitor, CS-719, which has shown good results in decreasing plasma glucose with the suppression of hepatic endogenous glucose production and gluconeogenesis in type 2 diabetic rodents may re-establish the FBPase subcellular distribution [Yoshida et al, 2011]. However, it is still unknown if CS-719 regulates the subcellular localization of FBPase.…”

Section: Discussionmentioning

confidence: 99%

Nuclear accumulation of fructose 1,6‐bisphosphatase is impaired in diabetic rat liver

Bertinat

Pontigo

Perez

et al. 2012

J of Cellular Biochemistry

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Using a streptozotocin-induced type 1 diabetic rat model, we analyzed and separated the effects of hyperglycemia and hyperinsulinemia over the in vivo expression and subcellular localization of hepatic fructose 1,6-bisphosphatase (FBPase) in the multicellular context of the liver. Our data showed that FBPase subcellular localization was modulated by the nutritional state in normal but not in diabetic rats. By contrast, the liver zonation was not affected in any condition. In healthy starved rats, FBPase was localized in the cytoplasm of hepatocytes, whereas in healthy re-fed rats it was concentrated in the nucleus and the cell periphery. Interestingly, despite the hyperglycemia, FBPase was unable to accumulate in the nucleus in hepatocytes from streptozotocin-induced diabetic rats, suggesting that insulin is a critical in vivo modulator. This idea was confirmed by exogenous insulin supplementation to diabetic rats, where insulin was able to induce the rapid accumulation of FBPase within the hepatocyte nucleus. Besides, hepatic FBPase was found phosphorylated only in the cytoplasm, suggesting that the phosphorylation state is involved in the nuclear translocation. In conclusion, insulin and not hyperglycemia plays a crucial role in the nuclear accumulation of FBPase in vivo and may be an important regulatory mechanism that could account for the increased endogenous glucose production of liver of diabetic rodents.

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Section: Discussionmentioning

confidence: 99%

Nuclear accumulation of fructose 1,6‐bisphosphatase is impaired in diabetic rat liver

Bertinat

Pontigo

Perez

et al. 2012

J of Cellular Biochemistry

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“…Gluconeogenesis GNG is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids [12]. It is widely known that the liver is a central organ in lipogenesis, gluconeogenesis and cholesterol metabolism Ref.…”

Section: Discussionmentioning

confidence: 99%

The relationship between ultraviolet, vitamin d and blood glucose, in vivo study

Bukhari

Khorshid²

2017

Trauma Emerg Care

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This study is carried on to investigate the effect of (UV) on the estimate of vitamin D production and the correlation ratio of vitamin D and its impact on the increase of blood glucose finally to prove the relationship via biochemical analysis of Vitamin D and glucose level. 90 adult rats were randomly divided into three groups. G1 (-ve control): This group contains 30 rats that were not exposed to the ultraviolet. Rats were eating daily/4 months. G2 (+ve control): This group contains 30 rats that were not exposed to the ultraviolet. Rats were fasting 2 days and eat the third day frequently (4 months). G3: Test group: To examine the exposed to the ultraviolet for 10 second to simulate sunrise and another 10 second to simulate sunset (using prototype cage). This group contains 30 rats, which were fasting 2 days and eat the third day frequently (4 months). Weights were recorder every week. The blood samples were collected through retro-orbital venous plexus in the zero time, every month, and at the end of four months and the obtained sera were subjected to the Glucose and D3 tests. The results showed that the body weights were reducing significantly in G1 compared with G3 at all measured periods (P < 0.000). Whereas no significant differences between G3 and G2 in all weeks. The Glucose levels in G1 and G3 were raised significantly in (1 st , 2 nd , 3 rd and 4 th month) (P< 0 .035), (P< 0 .036), (P< 0.030) and (P< 0.023). Also blood level of Glucose was raised significantly between G3 and G2 in all periods (P< 0 .008), (P< 0 .009), (P< 0.002) and (P< 0.001). Moreover the blood levels of Vitamin D between G1 and G3 were raised significantly in all tested periods (P< 0 .001), (P< 0 .000), (P< 0.000) and (P< 0.003). Also Vitamin D was raised significant (P< 0.000) in G3 compared with G2. This study was proved that vitamin D level was affected by the exposure to ultraviolet that intern affect the glucose level. Also ultraviolet (UV) extend to preservation of glucose homeostasis by raising glucose level. Accordingly ultraviolet (UV) raising vitamin D should be considered since this may help reduce the risk of glucose disorders.

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“…CS-917 is catalyzed to an intermediate form, R-134450, by the esterase enzyme and then to an active form, MB05032, by the phosphoramidase enzyme [ 143 ]. CS-917 has inhibited gluconeogenesis and improved fasting and postprandial hyperglycemia in preclinical trials [ 142 , 144 , 145 ]. Six phase 1/2 clinical trials of MB07803 have been completed [ 146 ].…”

Section: The Clinical Application Of Mir-26 Target Genes With a Focus...mentioning

confidence: 99%

The translational potential of miR-26 in atherosclerosis and development of agents for its target genes ACC1/2, COL1A1, CPT1A, FBP1, DGAT2, and SMAD7

Chen,

Wu,

et al. 2024

Cardiovasc Diabetol

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Atherosclerosis is one of the leading causes of death worldwide. miR-26 is a potential biomarker of atherosclerosis. Standardized diagnostic tests for miR-26 (MIR26-DX) have been developed, but the fastest progress has been in predicting the efficacy of IFN-α therapy for hepatocellular carcinoma (HCC, phase 3). MiR-26 slows atherosclerosis development by suppressing ACC1/2, ACLY, ACSL3/4, ALDH3A2, ALPL, BMP2, CD36, COL1A1, CPT1A, CTGF, DGAT2, EHHADH, FAS, FBP1, GATA4, GSK3β, G6PC, Gys2, HMGA1, HMGB1, LDLR, LIPC, IL-1β, IL-6, JAG2, KCNJ2, MALT1, β-MHC, NF-κB, PCK1, PLCβ1, PYGL, RUNX2, SCD1, SMAD1/4/5/7, SREBF1, TAB3, TAK1, TCF7L2, and TNF-α expression. Many agents targeting these genes, such as the ACC1/2 inhibitors GS-0976, PF-05221304, and MK-4074; the DGAT2 inhibitors IONIS-DGAT2Rx, PF-06427878, PF-0685571, and PF-07202954; the COL1A1 inhibitor HT-100; the stimulants 68Ga-CBP8 and RCT-01; the CPT1A inhibitors etomoxir, perhexiline, and teglicar; the FBP1 inhibitors CS-917 and MB07803; and the SMAD7 inhibitor mongersen, have been investigated in clinical trials. Interestingly, miR-26 better reduced intima-media thickness (IMT) than PCSK9 or CT-1 knockout. Many PCSK9 inhibitors, including alirocumab, evolocumab, inclisiran, AZD8233, Civi-007, MK-0616, and LIB003, have been investigated in clinical trials. Recombinant CT-1 was also investigated in clinical trials. Therefore, miR-26 is a promising target for agent development. miR-26 promotes foam cell formation by reducing ABCA1 and ARL4C expression. Multiple materials can be used to deliver miR-26, but it is unclear which material is most suitable for mass production and clinical applications. This review focuses on the potential use of miR-26 in treating atherosclerosis to support the development of agents targeting it.

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Contributions of Hepatic Gluconeogenesis Suppression and Compensative Glycogenolysis on the Glucose-Lowering Effect of CS-917, a Fructose 1,6-Bisphosphatase Inhibitor, in Non-obese Type 2 Diabetes Goto-Kakizaki Rats

Cited by 8 publications

References 23 publications

Nuclear accumulation of fructose 1,6‐bisphosphatase is impaired in diabetic rat liver

Nuclear accumulation of fructose 1,6‐bisphosphatase is impaired in diabetic rat liver

The relationship between ultraviolet, vitamin d and blood glucose, in vivo study

The translational potential of miR-26 in atherosclerosis and development of agents for its target genes ACC1/2, COL1A1, CPT1A, FBP1, DGAT2, and SMAD7

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