Altered glucose metabolism and insulin resistance in cancer-induced cachexia: a sweet poison

Masi, Tamhida; Patel, Bhoomika M.

doi:10.1007/s43440-020-00179-y

Cited by 50 publications

(34 citation statements)

References 124 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our data support a role for FOXO in atrophy, which is consistent with the studies mentioned above [17,57].Myotubes could be induced to hypertrophy by PI3K/Akt pathway, which increases protein synthesis and blocks the up-regulation of MAFbx and MuRF1 that occurs during muscle atrophy [20,54]. PI3K/AKT signaling leads to the activation of mTOR, p70S6, and various other pathways, which also promote muscle synthesis [59]. Our study showed that L-carnitine reverses TNF-α-induced muscle cell atrophy caused by regulating the Akt/P70S6K/FOXO3a pathways, and by inhibiting muscle-speci c ubiquitin ligases.…”

Section: Discussionsupporting

confidence: 91%

L-Carnitine Ameliorates the Muscle Wasting of Cancer Cachexia through the AKT/FOXO3a/MaFbx Axis

Zhu

et al. 2021

Preprint

View full text Add to dashboard Cite

Recent studies suggest potential benefits of applying L-carnitine in the treatment of cancer cachexia, but the precise mechanisms remain unknown. This study was conducted to determine the mechanism by which L-carnitine reduces cancer cachexia. We found that L-carnitine increased the gastrocnemius muscle (GM) weight in the CT-26-bearing cachexia mouse model and the cross-sectional fiber area (CFA) of the GM and myotube diameters of C2C12 cells treated with TNF-α. Additionally, L-carnitine reduced the protein expression of muscle RING-type E3 ubiquitin ligase 1 (MuRF1), muscle atrophy F-box protein (MaFbx) and FOXO3a, and increased the p-FOXO3a level in vivo and in vitro, indicating that L-carnitine inhibits muscle protein ubiquitination in models of cachexia. Inhibition of Akt, upstream of FOXO3a, reversed the effects of L-carnitine on the FOXO3a/MaFbx pathway and myotube diameters, without affecting FOXO3a/MuRF-1. In addition to regulating the ubiquitination of muscle proteins, L-carnitine also increased the levels of p-p70S6K and p70S6K, which are involved in protein synthesis. Akt inhibition did not reverse the effects of L-carnitine on p70S6K. Hence, L-carnitine ameliorated cancer cachexia via the Akt/FOXO3/MaFbx and p70S6K pathways. Moreover, L-carnitine reduced the serum levels of interleukin-1 (IL-1) and interleukin-6 (IL-6), factors known to induce cancer cachexia. However, there were minimal effects on TNF-α, another inducer of cachexia. Taken together, these results revealed a novel mechanism of action by which L-carnitine protects muscle cells and reduces inflammation related to cancer cachexia.

show abstract

Section: Discussionsupporting

confidence: 91%

L-Carnitine Ameliorates the Muscle Wasting of Cancer Cachexia through the AKT/FOXO3a/MaFbx Axis

Zhu

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…We verified MMP12 can degrade insulin or IGF-1 in vitro, which is consistent with the previous study (Kettner et al). As the two key hormones in tumor microenvironment, insulin resistance is correlated with in insufficient insulin, lack of insulin receptor, or decreased insulin sensitivity, which will reduce the uptake of glucose in organs, which suggests that MMP12 is closely related to glycolipid metabolism, leading to the loss of skeletal muscle and adipose tissue (Baker Rogers et al, 2020;Dev et al, 2019;Han et al, 2019;Masi and Patel, 2020;Takayama, 2019). The insulin kits and insulin tolerance test and oral glucose tolerance test results showed that the knocking out MMP12 in Apc Min/+ mice may reduce insulin levels or increase insulin sensitivity, reversing insulin resistance ( Figure 5-figure Supplement 6A-H), but is not related to basic function of islets according to H&E staining and IHC staining ( Figure 5-figure Supplement 4E-H).…”

Section: Discussionmentioning

confidence: 99%

“…Knockout of MMP12 can reduce muscle loss in Apc Min/+ mice. Recently, it has been demonstrated that insulin and insulin-like growth factor 1(IGF-1) have complex anabolic effects and are important regulators of muscle remodeling that can mediate muscle atrophy (Baker Rogers et al, 2020;Dev et al, 2019;Han et al, 2019;Masi and Patel, 2020;Takayama, 2019). Moreover, Jung-Ting Lee proposed that MMP12 expression significantly promoted insulin resistance and that insulin may be regulated by resident macrophages (Lee et al, 2014a).…”

Section: Mmp12 Can Degrade Insulin and Insulin-like Growth Factor-1mentioning

confidence: 99%

“…It is reported that insulin and insulin-like growth factor 1 can indeed affect the muscle loss caused by cachexia and exacerbate weight loss (Baker Rogers et al, 2020;Dev et al, 2019;Han et al, 2019;Masi and Patel, 2020;Takayama, 2019). Therefore, we are concerned about whether the inhibition of MMP12 that degrades insulin and insulin-like growth factor 1 affects the weight change of cachexia mice.…”

Section: Mmp12 Inhibitor Can Rescue Weight Loss Of Apc Min/+ Micementioning

confidence: 99%

See 1 more Smart Citation

MMP12 Knockout Prevent Weight and Muscle Loss Induced by Cancer Cachexia

Jiang

Yang

et al. 2021

Preprint

View full text Add to dashboard Cite

Weight loss and muscle wasting can have devastating impacts on survival and quality of life of patients with cancer cachexia. Here, we have established a hybrid mouse of ApcMin/+ mice and MMP12 knockout mice (ApcMin/+; MMP12-/-) and found that knockout MMP12 can suppress the weight and muscle loss of ApcMin/+ mice. In detail, we found that interleukin 6 was highly upregulated in the serum of cancer patients and MMP12 was increased in muscle of tumor-bearing mice. Interestingly, the interleukin 6 secreted by tumor cells led to MMP12 overexpression in the macrophages, which further resulted in degradation of insulin and insulin-like growth factor 1 and interruption of glycolipid metabolism. Notably, depletion of MMP12 prevented weight loss of ApcMin/+ mice. Our study uncovers the critical role of MMP12 in controlling weight and highlights the great potential of MMP12 in the treatment of cancer cachexia.

show abstract

“…This movement of glucose from the blood towards cells is aided by a hormone known as insulin. It has been observed that diabetic patients have a higher amount of glucose in their blood as compared to the blood glucose level of a normal person [5]. Such patients need more insulin to regularize their cell functions and to decrease the amount of glucose within the blood [6].…”

Section: Introductionmentioning

confidence: 99%

Computational Study of D-glucose and its Differential Cognitive Effects on Well-being and Quality of Life

et al. 2020

View full text Add to dashboard Cite

GAMESS computational chemistry package is a freeware available on the web. It has been successfully applied for the structure elucidation of the commonly available D-glucose. In the current research, IR and Raman spectra of D-glucose were theoretically calculated by utilizing the density functional theory (DFT), combined with B3LYP/3-21G basic set. IR and Raman activities were estimated through the GAMESS computational package. Moreover, the NMR spectrum was also obtained through the Gaussian 09 package. Theoretically calculated and experimentally calculated results were compared using the B3LYP/3-21G level of theory. The results of both calculations were nearly the same. The optimization of structure with the various levels of theory and Basis sets was studied and the best results were obtained using B3LYP/3-21G, and these results agreed considerably with the experimental results. The current computational analysis may be useful to predict complex carbohydrate precursors and other carbohydrate molecules.

show abstract

Altered glucose metabolism and insulin resistance in cancer-induced cachexia: a sweet poison

Cited by 50 publications

References 124 publications

L-Carnitine Ameliorates the Muscle Wasting of Cancer Cachexia through the AKT/FOXO3a/MaFbx Axis

L-Carnitine Ameliorates the Muscle Wasting of Cancer Cachexia through the AKT/FOXO3a/MaFbx Axis

MMP12 Knockout Prevent Weight and Muscle Loss Induced by Cancer Cachexia

Computational Study of D-glucose and its Differential Cognitive Effects on Well-being and Quality of Life

Contact Info

Product

Resources

About