Effects of low-carbohydrate diet and ketogenic diet on glucose and lipid metabolism in type 2 diabetic mice

Nutrition ◽  
2021 ◽  
pp. 111230
Author(s):  
Zi Yang ◽  
Jingyi Mi ◽  
Yu Wang ◽  
Lamei Xue ◽  
Jinxin Liu ◽  
...  
2017 ◽  
Vol 3 (1) ◽  
pp. 9-16 ◽  
Author(s):  
Hiroshi Bando ◽  
◽  
Koji Ebe ◽  
Tetsuo Muneta ◽  
Masahiro Bando ◽  
...  

2022 ◽  
Vol 28 (1) ◽  
Author(s):  
Jielin Zhou ◽  
Yao Lu ◽  
Yajing Jia ◽  
Jing Lu ◽  
Zhengxuan Jiang ◽  
...  

Abstract Background Previous reports implied a possible link between PES1 and lipid metabolism. However, the role of PES1 in regulating T2DM related lipid metabolism and the effect of ketogenic diet (KD) on PES1 have not been reported. The aim of present study is to explore the role of PES1 in effects of KD on diabetic mice and its mediated mechanism. Methods Male C57BL/6J and KKAy mice were fed with standard diet (SD) and KD, respectively. Simultaneously, McArdle 7777 cells were treated by β-hydroxybutyric acid (β-HB), Pes1 siRNA or Pes1 overexpression plasmid, respectively. Additionally, liver-conditional knockout (CKO) of Pes1 in vivo was applied. Results Hepatic PES1 expression in diabetic mice was markedly increased, which was suppressed by KD feeding with an accompanying reduction of hepatic and plasma triglycerides (TG). In mice with CKO of Pes1, the protein levels of p300, SREBP1c, FASN, SCD1, Caspase1, NLRP3 and GSDMD were dramatically downregulated in livers, and the plasma and hepatic TG, IL-1β and IL-18 were decreased as well. The similar outcomes were also observed in β-HB and Pes1 knockdown treated hepatocytes. By contrast, Pes1 overexpression in cultured hepatocytes showed that these levels were significantly enhanced, which were, however reduced under β-HB treatment. Mechanistically, we discovered that β-HB decreased CHOP binding to the Pes1 promoters, resulting in the downregulation of PES1, thereby reducing PES1 binding to p300 and Caspase1 promoters. The inhibition of p300 and Caspase1 expression elicited the dramatic suppression of acetylation of SREBP1c via its interaction with p300, and the decreased GSDMD levels. Besides, knockdown of Caspase1 also alleviated the TG levels in cultured hepatocytes. Conclusion KD may improve lipid dysregulation in type 2 diabetic mice by downregulating hepatic PES1 expression.


2021 ◽  
Author(s):  
Jielin Zhou ◽  
Yao Lu ◽  
Yajing Jia ◽  
Jing Lu ◽  
Zhengxuan Jiang ◽  
...  

Abstract Background: Previous reports implied a possible link between PES1 and lipid metabolism. However, the role of PES1 in regulation of T2DM related lipid metabolism and the effect of KD on PES1 have not been reported. The aim of present study is to explore the role of PES1 in effects of ketogenic diet (KD) on diabetic mice and its mediated mechanism.Methods: Male C57BL/6J and KKAy mice were fed with standard diet (SD) and KD, respectively. Simultaneously, McArdle 7777 cells were treated by β-hydroxybutyric acid (β-HB), Pes1 siRNA or Pes1 overexpression plasmid, respectively. Additionally, liver-conditional knockout (CKO) of Pes1 in vivo were used.Results: We unexpectedly found that hepatic PES1 expression in T2DM patients was markedly elevated, but the elevated PES1 was suppressed by KD feeding in T2DM mice with the reduction of hepatic and plasma triglycerides (TG). In mice with CKO of Pes1, the protein levels of p300, SREBP1c, FASN, SCD1, caspase1, NLRP3 and GSDMD were dramatically downregulated in livers, and the plasma and hepatic TG, IL-1β and IL-18 were decreased as well. The similar phenomena were also observed in β-HB and Pes1 knockdown treated hepatocytes. By contrast, Pes1 overexpression in cultured hepatocytes showed that these levels were significantly enhanced, which however were reduced under β-HB treatment. Mechanistically, we discovered that β-HB decreased CHOP binding to the Pes1 promoters, resulting in the downregulation of PES1, thereby reducing PES1 binding to p300 and caspase1 promoters. The inhibition of p300 and caspase1 expressions elicited the dramatic suppression of acetylation of SREBP1c via its interaction with p300, and the decreased GSDMD levels. Besides, knockdown of caspase1 also alleviated the TG levels in cultured hepatocytes.Conclusion: KD may improve lipid dysregulation in type 2 diabetic mice by downregulating hepatic PES1 expression.


2011 ◽  
Vol 93 (4) ◽  
pp. 844-850 ◽  
Author(s):  
Lawrence de Koning ◽  
Teresa T Fung ◽  
Xiaomei Liao ◽  
Stephanie E Chiuve ◽  
Eric B Rimm ◽  
...  

2020 ◽  
Vol 12 (12) ◽  
pp. 1445-1451
Author(s):  
Xiaofan Zhang ◽  
Youyou Zhang ◽  
Lingjia Gu ◽  
Haiying Tao ◽  
Shuang Zhu

Nanoparticles play a major role in drug delivery. We investigated the effects of the intelligent administration of insulin-loaded nanoparticles (ILNP) when combined with a low-carbohydrate diet (LCD) on the metabolism of patients with type 2 diabetes. ILNP and smart vesicle polymers were developed, and their properties were studied in vitro. Further clinical trials were performed, during which body mass index (BMI), fasting blood glucose (FBG) levels, and glycated hemoglobin (HbA1c) levels were compared between type 2 diabetes patients on LCDs those on normal diets. The results demonstrated that ILNP resisted protease degradation due to steric hindrance, and remained relatively stable at a pH range of 5.0 to 7.4. The nanoparticle enteric-coated capsules resisted the gastric juice acidity (pH = 2.5) and ensured the stable embedding of the insulin. The insulin was then released at a slightly higher pH (pH = 6.6), which mimicked the small intestine. Smart vesicle polymers further embedded the insulin and glucose oxidase simultaneously in nano polymer compounds, which allowed for a dose-dependent response to the concentration of glucose. Thus, the insulin was not released in a low-concentration glucose solution, but rather in a high-concentration glucose solution. Based on these results, we concluded that the clinical trial results showed that the intelligent administration of ILNP combined with a LCD reduced BMI, FBG, and HbA1c levels in patients with type 2 diabetes.


2019 ◽  
Vol 33 (11) ◽  
pp. 107415 ◽  
Author(s):  
Mizuho Kondo-Ando ◽  
Yusuke Seino ◽  
Risa Morikawa ◽  
Kana Negi ◽  
Hidechika Todoroki ◽  
...  

2020 ◽  
Vol 8 (1) ◽  
pp. e001303
Author(s):  
Toru Kusakabe ◽  
Shigefumi Yokota ◽  
Mika Shimizu ◽  
Takayuki Inoue ◽  
Masashi Tanaka ◽  
...  

IntroductionTreatment using sodium-glucose cotransporter (SGLT) 2 inhibitor and low-carbohydrate diet (LCD) for obesity and type 2 diabetes are similar in terms of carbohydrate limitation. However, their mechanisms of action differ, and the effects on the body remain unclear. We investigated the effects of SGLT2 inhibitor and LCD on body composition and metabolic profile using the db/db mouse model for obesity and type 2 diabetes.Research design and methodsEight-week-old male db/db mice were divided into four groups: mice receiving normal diet and vehicle or canagliflozin (Cana) administration and mice receiving LCD and vehicle or Cana administration for 8 weeks. Consumed calories were adjusted to be equal among the groups.ResultsBoth Cana administration and LCD feeding resulted in significant weight gain. Cana administration significantly decreased plasma glucose levels and increased plasma insulin levels with preservation of pancreatic β cells. However, LCD feeding did not improve plasma glucose levels but deteriorated insulin sensitivity. LCD feeding significantly reduced liver weight and hepatic triglyceride content; these effects were not observed with Cana administration. Combined treatment with LCD did not lead to an additive increase in blood β-ketone levels.ConclusionsSGLT2 inhibitors and LCD exert differential effects on the body. Their combined use may achieve better metabolic improvements in obesity and type 2 diabetes.


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