• Korean Journal of Clinical Laboratory Science
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• v.53 no.1
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• pp.81-87
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• 2021

The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide. T2DM is one of the most common types of diabetes and is caused by increased insulin resistance and reduced insulin secretion. Peroxisome proliferator-activated receptor γ coactivator 1 alpha (PPARGC1A) is a master modulator of mitochondrial biogenesis and of gluconeogenesis in liver. In this study, we analyzed genetic polymorphisms of PPARGC1A gene in a middle-aged Korean population with T2DM. Using the genotype data of 736 T2DM cases and 4544 healthy controls obtained from the Korean Association Resource (KARE), we analyzed genetic correlations between single nucleotide polymorphisms (SNPs) of PPARGC1A and T2DM. Fifteen SNPs of PPARGC1A demonstrated a statistically significant association with T2DM. Of these, rs10212638 exhibited the strongest correlation with T2DM (P-value=0.015, OR=1.29, CI=1.05~1.59), and the minor G allele of PPARGC1A increased the risk of T2DM. This is the first study to report a significant association between genetic polymorphisms in PPARGC1A and T2DM and suggests that SNPs of PPARGC1A display genetic correlations to the etiology of T2DM.

• Journal of Korean Medicine for Obesity Research
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• v.23 no.2
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• pp.60-68
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• 2023

Objectives: This study was conducted to compare the effects of Hominis placenta (Jahage, J) and wild ginseng (SanSam, S) pharmacopuncture drugs on muscle differentiation and energy metabolism regulation in C2C12 myotubes. Methods: The C2C12 myoblasts were differentiated into myotubes for 5 days by replacing in medium containing 2% horse serum and then treated with J and S pharmacopuncture extract at different concentrations for 24 hr. The expression of myosin heavy chain and energy metabolism-regulating factors, myosin heavy chain (MHC), nuclear respiratory factor-1 (NRF-1), and proliferator-activated receptor γ coactivator-1 alpha (PGC-1α) were determined in C2C12 myotubes by western blot. Additionally, the phosphorylation of AMPK and the expression of mitochondrial biogenesis, including sirtuin 1 (SIRT1) were determined in the myotubes. Results: As a result, treatment with J and S pharmacopuncture extract at 0.1 and 1 mg/mL increased the MHC expression in C2C12 myotubes compared with non-treated cells, but only S pharmacopuncture was shown a significant and distinct increase in the expression. Expression of TFAM and NRF-1 was also shown significant increases in S and J pharmacopuncture in C2C12 myotubes compared to non-treated cells. The phosphorylation of AMPK and the expression of PGC-1α and SIRT1 showed increased expression in S and J pharmacopuncture compared to non-treated cells. The effect of low-dose of J pharmacopuncture on the phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and PGC-1α expression was greater than that of S pharmacopuncture. Conclusions: In conclusion, both J and S pharmacopuncture promote muscle differentiation in C2C12 myoblasts into myotubes and energy metabolism through the AMPK/SIRT1 signaling pathway. This indicates that the pharmacopuncture with tonic herbal medicines can help to improve skeletal muscle function.

• Journal of Life Science
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• v.31 no.9
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• pp.818-826
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• 2021

5-Aminolevulinic acid phosphate (5-ALA-p) is a substance obtained by eluting 5-ALA (a natural delta amino acid) with aqueous ammonia, adding phosphoric acid to the eluate, and then adding acetone to confer properties suitable for use in photodynamic therapy applications. However, its pharmacological efficacy, including potential mechanisms of antioxidant and anti-inflammatory reactions, remains unclear. This study aimed to investigate the effects of 5-ALA-p on oxidative and inflammatory stresses in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Our data showed that 5-ALA-p significantly inhibited excessive phagocytic activity via LPS and attenuated oxidative stress in LPS-treated RAW 264.7 cells. Furthermore, 5-ALA-p improved mitochondrial biogenesis reduced by LPS, suggesting that 5-ALA-p restores mitochondrial damage caused by LPS. Additionally, 5-ALA-p significantly suppressed the release of nitric oxide (NO) and pro-inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β, and IL-6, which are associated with the inhibition of inducible NO synthase and respective cytokine expression. Furthermore, 5-ALA-p reduced the nuclear translocation of nuclear factor-kappa B (NF-κB) and inhibited phosphorylation of mitogen-activated protein kinases (MAPKs), indicating that the anti-inflammatory effect of 5-ALA-p is mediated through the suppression of NF-κB and MAPK signaling pathways. Based on these results, 5-ALA-p may serve as a potential candidate to reduce inflammation and oxidative stress.

• Journal of Life Science
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• v.21 no.3
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• pp.435-443
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• 2011

The purpose of this study is to identify the effects of exercise training [ET, 10~18 m/min (speed), 20~30 min (exercise duration)/a day for 5 day/wk, 6 wk) on PGC-$1{\alpha}$, GLUT-1, Tfam, Cu,Zn-SOD and Mn-SOD proteins in brain of STZ-induced diabetic rats. The male Sprague-Dawley (SD) rats were single-injected intraperitoneally with 50mg/kg of streptozotocin (STZ) to produce STZ-induced diabetic rats. Rats were divided into 3 experimental groups with 8 rats in each group, as follows: (1) non-STZ group (n=8), (2) STZ-CON group (n=8), (3) STZ-EXE group (n=8). The results of this study suggest that i) serum glucose level was significantly reduced in STZ-EXE group compared with STZ-CON group (p<0.05), ii) PGC-$1{\alpha}$ (p<0.001), mtPGC-$1{\alpha}$ (p<0.001), GLUT-1 (p<0.001), and mtTfam (p<0.001) proteins in brain of STZ-induced diabetic rats were significantly increased in STZ-EXE group compared with STZ-CON group, iii) Cu,Zn-SOD (p<0.001) and Mn-SOD (p<0.01) proteins in the STZ-induced diabetic rats were significantly increased in STZ-EXE group compared with STZ-CON group. In conclusion, the findings of the present study reveal that treadmill exercise training increases brain GLUT-1 protein level possibly through up-regulation of PGC-$1{\alpha}$ and Tfam proteins which represent key regulatory components of stimulation of brain mitochondrial biogenesis. In addition, treadmill exercise training may prevent oxidative stress by up-regulation of Cu,Zn-SOD and Mn-SOD proteins in the STZ-induced diabetic rats.