Research ArticleExperimental Studies
Open Access

Ginger Supplementation Attenuated Mitochondrial Fusion and Improved Skeletal Muscle Size in Type 2 Diabetic Rats

CASEY R. APPELL, NIGEL C. JIWAN, RUI WANG, CHWAN-LI SHEN and HUI-YING LUK
In Vivo January 2024, 38 (1) 73-81; DOI: https://doi.org/10.21873/invivo.13412

Abstract

Background/Aim: Oxidative stress, regulated by SOD2 and mitochondrial dynamics, contributes to muscle atrophy in diabetes. Ginger root extract (GRE) reduces oxidative stress. However, its effect on oxidative stress, mitochondrial dynamics, and muscle atrophy is not known in the diabetic muscle. This study examined the effect of GRE on intramuscular oxidative stress, mitochondrial dynamics, and muscle size in diabetic rats. Materials and Methods: Twenty-six male Sprague-Dawley rats were randomly divided into control diet (CON; n=10), high-fat diet with one dose of 35 mg/kg streptozotocin (HFD; n=9), and high-fat diet with one dose of 35 mg/kg streptozotocin and 0.75% w/w GRE (GRE; n=7) fed for seven weeks. Subsequently, the muscle was analyzed for cross-sectional area (CSA), H2O2 concentration, and DRP-1, MFN2, Parkin, PINK1, SOD2 mRNA. Additionally, the protein levels of SOD2, DRP-1, DRP-1ser616, LC3AB, MFN2, OPA1, Parkin, and PINK1 were analyzed. CSA, H2O2 concentration, and gene and protein expression levels were analyzed using a one-way ANOVA. Correlations among intramuscular H2O2, CSA, and SOD2 protein were assessed using Pearson’s bivariate correlation test. Results: In the soleus, the GRE group had a greater CSA and lower intramuscular H2O2 concentration compared to the HFD group. Compared to the HFD group, the GRE group had higher SOD2 and DRP-1 mRNA levels and lower MFN2 and total OPA1 protein levels. H2O2 concentration was negatively correlated with CSA and positively correlated with SOD2. Conclusion: GRE attenuated intramuscular H2O2, mitochondrial fusion, and muscle size loss. These findings suggest that GRE supplementation in diabetic rats reduces oxidative stress, which may contribute to muscle size preservation.

Key Words:

Oxidative stress contributes to the pathogenesis of type 2 diabetes (1-4), at least partly, by outpacing the resident mitochondrial anti-oxidative defense mechanism (e.g., SOD2) (5). Accumulation of reactive oxygen species (ROS) (e.g., superoxide anion, hydrogen peroxide) results in oxidative stress-induced cellular damage (that is, lipids, proteins, and nucleic acids) (6-9). Damage to these cellular components leads to the activation of catabolic (that is, autophagy) (10) and apoptotic (6) pathways that can result in muscle atrophy (7-9, 11). Given that the skeletal muscle is the major glucose disposal site (12), muscle atrophy can exacerbate insulin resistance in individuals with type 2 diabetes (8, 9).

Superoxide anion (O2−) is primarily generated during mitochondrial metabolism (13) and is converted to H2O2 (14) by SOD2 in the mitochondria (15). Catalase then converts H2O2 into water and oxygen (16). In conjunction with SOD2, improved mitochondrial dynamics (that is, fusion, fission, and mitophagy) has been shown to alleviate oxidative stress (17). During short-term oxidative stress, mitochondria transiently increase mitofusion2 (MFN2) [that is, indicative of mitochondrial fusion (18)] to increase anti-oxidant processes and reduce O2− concentration (19). Under a prolonged oxidative stress, an increase in dynamin-related protein-1 (DRP-1) [that is, indicative of mitochondrial fission (20)] and mitophagy associated proteins (that is, PTEN-induced kinase 1: PINK1, Parkin RBR E3 ubiquitin-protein ligase: Parkin, and Microtubule-associated protein 1 light chain 3 AB: LC3B) selectively degrade the damaged portion of mitochondria to prevent further oxidative stress (19, 21, 22). Moreover, disruption of mitochondrial dynamics has been shown to increase production of ROS (17, 23). In type 2 diabetic rodent models, disrupted mitochondrial dynamics (that is, lower MFN2 and greater DRP-1), indicated by smaller mitochondrial size, was associated with greater ROS (2, 24, 25). We have previously reported that compared to healthy controls, type 2 diabetic rats have increased mitochondrial fission, which could contribute to the smaller muscle size (26). The accumulation of ROS could trigger proteolytic and apoptotic signaling cascades (18), and result in muscle atrophy (3), which has been observed in individuals with type 2 diabetes (9, 27). Notably, Gupta et al., reported that alleviating H2O2 induced oxidative stress attenuated the activation of proteolytic systems (that is, autophagy) and attenuated myofiber atrophy in vitro (28).

Ginger root extract is a robust anti-oxidant compound that has been shown to scavenge O2− and H2O2 in vitro (29-32), and is functionally similar to SOD2 and catalase, respectively (33). Notably, Račková et al. reported that ginger scavenged ROS, which was associated with preserved cell viability in-vitro (33). In individuals with type 2 diabetes, ginger supplementation decreased serum concentration of malondialdehyde [that is, a measure of ROS (34, 35)]. In chemically-induced muscle damage and aging rodent models, ginger supplementation attenuated DNA and mitochondria damage (that is, markers of reduced oxidative stress) (36, 37).

The factors contributing to muscle mass loss in patients with type 2 diabetes are multifaceted. Oxidative stress and disrupted mitochondrial dynamics contribute to skeletal muscle atrophy in diabetic models (7, 24). Ginger supplementation has been shown to reduce circulating oxidative stress in individuals with type 2 diabetes (35) as well as attenuate mitochondrial damage in aged and chemically-induced muscle damage rodent models, but not in type 2 diabetic models (36, 37). Therefore, the purpose of the current study was to examine the effects of GRE on intramuscular oxidative stress, mitochondrial dynamics, and muscle size in type 2 diabetic rats.

Materials and Methods

Animals and treatments. The detailed protocol has been published previously (26). Briefly, thirty Sprague-Dawley rats were randomly assigned to three groups: control group (CON), high-fat diet (HFD) and ginger root extract (GRE) groups. The CON group was fed a standard AIN-93G diet (10% calories from fat). The HFD group was injected with streptozotocin (STZ) and fed a diet that consisted of 45% calories from fat w/w diet (Cat. # 12451, Research Diets, New Brunswick, NJ, USA). The GRE group was injected with STZ (HFD) and fed a diet that contained 0.75% GRE (Ginger root extract 20%; Lot #G190297, Sabinsa Corporation, East Windsor, NJ, USA) and 45% calories from a fat w/w diet (Cat. # 12451, Research Diets). Each group was fed with the respective diet for 7 weeks. In rodent models, the combination of low dose STZ and high-fat diet has been previously shown to induce type 2 diabetes (e.g., increase fasting blood glucose and insulin concentration, etc.) (38-40). Fasting blood sugar levels above 200 mg/dl were considered diabetic and were tested 42-72 h after STZ injection. One rat from the HFD group and three rats from the GRE group were excluded because their fasting blood glucose levels (that is, CON; n=10, HDF; n=9, GRE; n=7) were below the 200 mg/dl. Rats in the HFD and GRE groups were confirmed to have diabetes (41). Briefly, the HFD group had a greater fasting blood glucose area under the curve compared to CON and GRE groups. These results suggest that HFD impaired glucose tolerance and supplementation of ginger attenuated the increase in fasting blood glucose (41). All conditions and handling of the animals were approved by the Texas Tech University Health Sciences Center Institutional Animal Care and Use Committee. All experiments were performed by the relevant guidelines and regulations.

To reduce the number of animals sacrificed, CON and HFD animals were used as described by Jiwan et al. (26) in accordance with the 3Rs method (42). A comparison between CON and HFD groups has been previously reported for muscle cross-sectional area (CSA), gene expression of NF-Embedded ImageB, IL-1β, IL-6, TNF-α, SOD2, MFN2, DRP1, PINK1, Parkin, LC3A, and LC3B, and protein levels of OPA1, MFN2, PINK1, Parkin, LC3AB, IL-1β, IL-6, and SOD2 (26). Briefly, for the soleus, the HFD group had a smaller CSA, lower SOD2, DRP-1, and MFN2 mRNA expression than the CON group. For the gastrocnemius, the HFD group had a greater Pink1 mRNA expression than the CON group. These results confirmed that the rats in the HFD group experienced muscle atrophy and altered mitochondrial dynamics. This report is focused on the effect of ginger root extract supplementation on ROS levels, mitochondria dynamics (that is, markers for fusion, fission, and mitophagy), and muscle size in diabetic rats.

Sample collection. Left soleus muscles were harvested, cleaned of adhering connective tissues, and frozen in the Tissue-Tek optimal cutting temperature (O.C.T.) compound (Cat. # 62550-01, Sakura, Torrance, CA, USA). Additionally, the right soleus and right gastrocnemius muscles were harvested, cleaned of adhering connective tissues, and were flash frozen in liquid nitrogen. All samples were stored at −80°C for later analyses.

CSA analysis. A detailed description of the Hematoxylin and Eosin staining protocol has been previously published (43). Briefly, previously frozen soleus muscle samples in O.C.T. compound were sectioned (10 μm thick) at −25°C in a cryostat and placed on positively charged microscope slides (Cat. # 22-037-246, ThermoFisher Scientific, Waltham, MA, USA). The CSA of gastrocnemius muscle was not analyzed due to limited samples. Slides were incubated with hematoxylin solution (Cat. # 3530-16, RICCA Chemical Company, Arlington, TX, USA) for 5 min, followed by a 10-min wash in warm tap water to stain the nuclei. The slides were then incubated with 0.5% Eosin solution (Cat. # se23-5001, ThermoFisher Scientific) with 1:100 acetic acid for 10-min. Slides were rinsed with deionized water and then allowed to air dry for 5-min. Finally, a coverslip was mounted with a mounting medium. Muscle samples were imaged at 5X magnification using a Zeiss Axiovert 200m Inverted Fluorescent Motorized Microscope (Ziess, Dublin, CA, USA). In total, 100 muscle fibers in each sample were measured for the CSA using ImageJ software (ver. 1.8.0_172; National Institute for Health, Bethesda, MD, USA). Data were normalized to the CON group.

H2O2 analysis. H2O2 concentrations in soleus samples were measured as per manufacturer instructions (Cat. # ab102500, Abcam, Cambridge, UK), using the colorimetric method. Briefly, homogenized soleus muscles were centrifuged (5-min, 2,000 × g, 4°C) and immediately deproteinated. Acids were precipitated and separated by centrifugation (15-min, 13,000 × g, 4°C). Samples were diluted in assay buffer 1:2, with 50 ml of reaction mix added to 50 ml of sample. Samples were analyzed in duplicate for technical replications. Plates were read at 570 nm using Bio-Tek Epoch microplate spectrophotometry (Agilent, Santa Clara, CA, USA). Data was normalized to the CON group.

PCR analysis. A detailed description of muscle tissue homogenization and RNA isolation has been published previously (44). Pre-designed assays for DRP-1, MFN2, Parkin, PINK1, SOD2 were obtained from Integrated DNA Technologies with beta-actin (Act-b) as the internal control. Samples were analyzed in duplicate for technical replications. Data were analyzed using the relative mRNA method and expressed as fold change versus the average expression of the CON group.

Western blot analysis. Due to a limited number of samples, a total of twenty-one Sprague-Dawley rats were used for western blot analysis (CON; n=7, HFD; n=7, GRE; n=7). A detailed description of muscle homogenization and western blot analyses have been published previously (45). Immunoblotting was carried out using rabbit monoclonal antibodies against DRP-1 (1:1,000; Cat. # 8570S, Cell Signaling Technologies, Danvers, MA, USA), phosphorylated DRP-1ser616 (1:1,000; Cat. # 3455, Cell Signaling Technologies), LC3AB (1:1,000; Cat. #12741, Cell Signaling Technologies), MFN2 (1:1,000; Cat. # 9482S, Cell Signaling Technologies), total OPA1 (1:1,000; Cat. # 80471S, Cell Signaling Technologies), Parkin (1:1,000; Cat. # 4211, Cell Signaling Technologies), PINK1 (1:1,000; Cat. # NB100-493, Novus Biologicals, St. Louis, MO, USA), SOD2 (1:1,500; Cat. # MAB3419, R&D Systems, Minneapolis, MN, USA), and GAPDH (1:4,000; Cat. # 8884, Cell Signaling Technologies). Densitometry data for each protein was normalized to GAPDH and then normalized to the average of the control group.

Statistics. SPSS (IBM version 22; IBM Corp, Armonk, NY, USA) was used for all statistical analyses. Soleus muscle CSA, H2O2 concentration, gene expression, and protein expression, were analyzed using a one-way analysis of variance. Bonferroni post hoc tests were used for pairwise comparisons. Additionally, Pearson’s correlation coefficient was generated to determine associative relationships between muscle CSA and H2O2 concentration as well as H2O2 concentration and SOD2 protein content. The statistical significance was set at p<0.05. Data are reported as mean±SE.

Results

Muscle cross-sectional area (CSA). For soleus, the HFD group (0.56±0.02 μm2) had a significantly smaller (p<0.05) CSA than the GRE group (0.89±0.06 μm2; p<0.0001). No difference was observed between CON and GRE groups. Soleus muscle CSA results are shown in Figure 1.

Figure 1.
Figure 1.

Soleus muscle cross-sectional area. Soleus muscle fiber cross-sectional area (μm2) (A). Average muscle fibers (n=100) counted per rat. Data were normalized to CON. Values are reported as mean±SEM (CON: n=7; HFD: n=7; GRE: n=7). *p<0.05 vs. GRE.

H2O2 analysis. For soleus, H2O2 concentration was significantly different between the groups. The HFD group (0.77±0.13 μM) had a significantly greater H2O2 concentration than the CON (0.25±0.11μM; p<0.0001) and GRE (0.63±0.16 μM; p=0.048) groups (Figure 2). No difference was observed between CON and GRE groups. Soleus H2O2 concentration assay results are shown in Figure 2.

Figure 2.
Figure 2.

Soleus muscle H2O2 concentration (μM). Data were normalized to CON. Values are reported as mean±SEM (CON: n=7; HFD: n=7; GRE: n=7). *p<0.05 vs. GRE, #p<0.05 vs. CON.

Oxidative stress. For soleus, mRNA expression of SOD2 was significantly different in the HFD group compared to GRE. Regarding SOD2, the HFD group (0.65±0.08) had significantly lower levels of SOD2 mRNA than the GRE group (1.03±0.20; p=0.032) with no difference between CON and GRE groups. For soleus and gastrocnemius, the protein levels of SOD2 were not significantly different in CON or HFD compared to GRE. Results observed for soleus SOD2 expression are shown in Figure 3. For gastrocnemius, no significant difference was observed for SOD2 mRNA expression in in the HFD group when compared to GRE group.

Figure 3.
Figure 3.

Soleus muscle mRNA expression results for SOD2 (A). Data were normalized to CON. Values are reported as mean±SEM (CON: n=7; HFD: n=7; GRE: n=7). *p<0.05 vs. GRE.

Fusion and fission. For soleus, the protein levels of MFN2 and total OPA1 were significantly different in CON and HFD compared to GRE. The levels of MFN2 in the HFD group (2.06±0.31) were significantly greater than those in the GRE (1.41±0.23; p=0.050), whereas no difference was observed between CON and GRE groups. The levels of total OPA1 in the GRE group (0.78±0.01) were significantly lower than those in the CON (1.00±0.06; p<0.0001) and HFD (1.01±0.08; p<0.0001) groups. Representative blots and quantification of the results for soleus MFN2 and OPA1 are shown in Figure 4. For gastrocnemius, no significant difference was observed for MFN2 and total OPA1 protein levels between the groups. For soleus and gastrocnemius, the protein levels of DRP-1, DRP-1ser616 or the ratio of DRP-1ser616 to total DRP-1 were not significantly different between groups. Table I summarizes normalized densitometry data (that is, mean±SEM) of all proteins measured. For soleus, the mRNA levels of DRP-1 in the GRE group (0.95±0.22) were not significantly different from those in the CON (1.00±0.04) and HDF (0.61±0.09) groups. No significant difference was observed for MFN2 mRNA expression in CON or HFD compared to GRE for soleus. Table II summarizes fold-change data (that is, mean±SEM) of all mRNA measured (Table II).

Figure 4.
Figure 4.

Protein levels of MFN2 (A), and total OPA1 (B) in the soleus. Data were normalized to CON. The western blots display an example of the protein levels of MFN2 (A), OPA1 (B), and the corresponding GAPDH in the CON, HFD, and GRE groups. The duplicate was run on the same gel for all conditions. Values are reported as mean±SEM (CON: n=7; HFD: n=7; GRE: n=7). MW, molecular weight (kDa). *p<0.05 vs. GRE.

View this table:
Table I.

Summary of protein densitometry data for DRP-1, LC3a, LC3b, MFN2, total OPA1, Parkin, Pink1, and SOD2 in the soleus and gastrocnemius muscles.

View this table:
Table II.

Summary of DRP-1, MFN2, Parkin, Pink1, and SOD2 mRNA expression in the soleus and gastrocnemius muscles.

For gastrocnemius, mRNA expression of MFN2 was significantly different in CON compared to GRE. The mRNA levels of MFN2 in the GRE group (1.62±0.24) were significantly greater than those in the CON group (1.00±0.05; p=0.009). Results observed for gastrocnemius MFN2 expression are shown in Figure 5. No significant difference in CON or HFD was observed for mRNA expression of DRP-1 compared to GRE for gastrocnemius. Summary data for protein densitometry and mRNA are reported in Table I and Table II, respectively.

Figure 5.
Figure 5.

Gastrocnemius muscle MFN2 mRNA expression (A). Data were normalized to CON. Values are reported as mean±SEM (CON: n=7; HFD: n=7; GRE: n=7). *p<0.05 vs. GRE.

Mitophagy. For soleus and gastrocnemius, the protein content of LC3A, LC3B, Parkin, and PINK1 were not significantly different in CON or HFD compared to GRE. For soleus and gastrocnemius, no significant difference in CON or HFD was observed for Parkin, Pink1 mRNA expression compared to GRE.

Pearson’s correlations. For soleus, a significant negative correlation (R2=0.33; p=0.004) was observed between H2O2 concentration and CSA. Additionally, a significant positive correlation (R2=0.20; p=0.026) was observed between H2O2 concentration and SOD2 protein content.

Discussion

Ginger supplementation scavenges O2− (29-31) and has been shown to attenuate muscle atrophy in chemically-induced atrophy rodent models (36, 37). Accumulation of oxidative stress (i.e., O2−, H2O2) results in cellular damage (46), leading to muscle atrophy (7-9, 11, 47). In the current report, when diabetic rats were supplemented with ginger, H2O2 concentration was lower than diabetic rats without ginger supplementation. In addition, H2O2 concentration was negatively associated with muscle size (i.e., CSA) and positively associated with SOD2 protein levels. Moreover, mitochondrial fusion was also attenuated (i.e., lower MFN2 and OPA1) in ginger supplemented diabetic rats. Together, these findings suggested that ginger supplementation attenuated diabetic-related muscle size loss which, at least partly, was contributed by alleviating the oxidative stress.

In healthy muscle, O2− is reduced to H2O2 by SOD2 that is further reduced to water and oxygen by catalase (48). This redox reaction is aligned with our data of a positive correlation between H2O2 concentration and SOD2 protein levels. Despite SOD2 transcript abundance was different between groups, the lack of change in SOD2 protein levels could be contributed by the product (i.e., H2O2) inhibition regulation. Ji et al. have reported that H2O2 -activated miR-146a resulted in SOD2 translation inhibition (49). In this report, H2O2 concentration remained elevated in GRE and HFD groups compared to CON group and could inhibit SOD2 transcription. Given that no difference in the protein levels of SOD2 was observed, the accumulation of H2O2 rats could be a result of catalase activity (50). Khadem et al. and Kim et al. observed that catalase activity was lower in diabetic rats compared to control (51, 52). Moreover, the enzymatic rate constant of catalase to reduce H2O2 is approximately two orders of magnitude less than that of SOD2 (i.e., 2.5×107 M−1 s−1, 2×109 M−1 s−1 respectively) (53, 54). Together, lower enzymatic activity and rate constant of catalase could result in a bottleneck effect potentially leading to the greater H2O2 concentration observed. Ginger, being able to reduce O2− to H2O2 and H2O2 to water and oxygen in vitro (29-32), at least partly, could account for the lower H2O2 concentration observed in this report.

Besides ROS reduction, mitochondria dynamics (i.e., fusion, fission, and mitophagy) have been shown to contribute to the prevention of the accumulation of ROS (17). When diabetic rats were supplemented with ginger, a reduction in H2O2 concentration was observed with a concomitant attenuated reduction of mitochondrial fusion (that is, MFN2 and total OPA1 proteins). Additionally, mitochondrial fission (DRP-1 mRNA) trended (p=0.067, Cohen’s d=0.45) to be lower in diabetic rats with ginger supplementation. Kawther et al. reported that following statin-induced ROS, mitochondria exhibit morphology consistent with unhealthy mitochondria (that is, accumulation of giant mitochondria with destructed cristae) (36). However, in the same study when statins were given ginger supplementation, ginger attenuated statin-induced ROS and improved mitochondrial health (that is, normal sized mitochondria with intact cristae) (36). In the current report, the supplementation of GRE reduced ROS which could promote mitochondrial fusion and thus alleviate the accumulation of unhealthy mitochondria in diabetic rats. This observation is aligned with previous studies that demonstrated ginger supplementation improved mitochondrial health, despite ROS was not directly measured, in aging and chemically-induced damage models (38, 39). A previous study demonstrated that DRP-1 mediated mitophagy by recruiting essential upstream mitophagy proteins (that is, Pink1, Parkin) (55). Therefore, the lack of change in soleus DRP-1 or DRP-1ser616 protein in this report could potentially indicate that ginger-mediated ROS reduction might have a minimal effect on mitophagy (i.e., LC3a, LC3b, Pink1, Parkin). Together, H2O2 accumulation-induced oxidative stress could, at least partly, contribute to muscle atrophy in diabetic muscle and ginger supplementation can mitigate muscle atrophy potentially through ginger’s anti-oxidative effects.

In gastrocnemius muscle, while the GRE group had greater mitochondrial fusion transcript abundance (MFN2) than the HFD and CON groups, no difference in MFN2 protein content was observed. Compared to soleus muscle, the increase in MFN2 transcript abundance could prevent the reduction in MFN2 protein observed in the gastrocnemius muscle. Slow-twitch (that is, soleus) oxidative muscles contain about 5 fold more mitochondria than fast-twitch (i.e., gastrocnemius) glycolytic muscles (56). Fewer mitochondria generate less ROS (57), which at least partly, could result in minimal changes to mitochondrial dynamics in the gastrocnemius compared to soleus. Pink1, a key mitophagy protein, plays also a role in mitochondrial trafficking (58). Pink1 phosphorylates Mitochondrial Rho GTPase to arrest mitochondrial motility (59). Immobile depolarized mitochondrion are less likely to undergo fusion with healthy mitochondria, which may mitigate the spread of damaged mitochondrial fragments (60). Speculatively, ginger supplementation in diabetic rats could activate Pink1-mediated mitochondria immobilization to isolate mitochondrial damage in muscle fibers, which rely less on oxidative phosphorylation for energy production.

In summary, the current findings illustrate that ginger supplementation in diabetic rats results in lower levels of ROS and larger muscle size compared to diabetic rats without ginger in the diet. Additionally, ginger supplementation lowered mitochondrial fusion. Given that mitochondria undergo fusion, in part, to reduce oxidative stress (19), greater ROS scavenging may lower the demand for mitochondrial fusion in ginger supplemented diabetic rats. Additionally, as the accumulation of oxidative stress can result in muscle atrophy (7-9, 11), greater ROS scavenging could mitigate oxidative stress-induced muscle atrophy in ginger supplemented diabetic rats.

Acknowledgements

This project was supported by the Texas Tech University startup funds.

Footnotes

  • Authors’ Contributions

    H.Y.L and C.L.S. conceived and designed the research. C.L.S. & R.W. conducted data collection. C.R.A., C.L.S., R.W., H.Y.L., N.C.J collected samples. C.R.A., H.Y.L., and N.C.J. performed sample and data analysis. C.R.A. and H.Y.L. wrote the manuscript. C.R.A., N.C.J., C.L.S., R.W., and H.Y.L. reviewed the draft. All Authors read and approved the manuscript.

  • Conflicts of Interest

    No conflicts of interest, financial or otherwise, are declared by the Authors. Additionally, the results of the report are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation.

  • Received September 28, 2023.
  • Revision received October 24, 2023.
  • Accepted November 6, 2023.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).

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Ginger Supplementation Attenuated Mitochondrial Fusion and Improved Skeletal Muscle Size in Type 2 Diabetic Rats
CASEY R. APPELL, NIGEL C. JIWAN, RUI WANG, CHWAN-LI SHEN, HUI-YING LUK
In Vivo Jan 2024, 38 (1) 73-81; DOI: 10.21873/invivo.13412
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