Effect of Lupinus rotundiflorus gamma conglutin treatment on JNK1 gene expression and protein activation in a rat model of type 2 diabetes

The effects of chronic coffee exposure in models of type 2 diabetes mellitus (T2D) models is scarcely studied, and the efficacy of the main coffee species has never been compared. We tested the hypothesis that long-term consumption of arabica and robusta coffee may differentially delay and affect T2D development in Zucker diabetic fatty rats. Three study groups received either chow mixed with arabica or robusta instant coffee (1.8% w/w) or unsupplemented chow food for 10 weeks. Both coffee species reduced liver triglyceride content and area under the curve of fasting and postprandial insulin. At study end, plasma adiponectin, total cholesterol and high density lipoprotein levels were higher in the robust group compared with both arabica and control groups. The liver gene expression of Glucose-6-phosphatase, catalytic subunit (G6pc) and Mechanistic target of rapamycin (mTOR) in robusta and Cpt1a in both coffee groups was downregulated. In conclusion, long-term consumption of both coffee species reduced weight gain and liver steatosis and improved insulin sensitivity in a rat model of T2D. Robusta coffee was seemingly superior to arabica coffee with respect to effects on lipid profile, adiponectin level and hepatic gene expression.

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The Pattern of Peroxisome Proliferator-activated Receptor Gamma Coactivator 1-alpha Gene Expression in Type-2 Diabetes Mellitus Rat Model Liver: Focus on Exercise

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2021.6362 ◽

2021 ◽

Vol 9 (T3) ◽

pp. 124-128

Author(s):

Yetty Machrina ◽

Dharma Lindarto ◽

Yunita Sari Pane ◽

Novita Sari Harahap

Keyword(s):

Gene Expression ◽

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Rat Model ◽

Moderate Intensity ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Treatment Groups

BACKGROUND: Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) has an important role in mitochondria biogenesis which generated cellular metabolism. Carbohydrate metabolism in the liver is crucial to maintain plasma blood glucose. AIM: This research aimed to determine the expression of PGC-1α gene in the liver type-2 diabetes mellitus (T2DM) rat model, after treatment with a focus on exercise. METHODS: We used 25 healthy male Wistar rats as subjects. Rats were modified to T2DM models by feeding a high-fat diet and low-dose streptozotocin injection. We divided the rats into five groups, that is, sedentary group as a control and four others as treatment groups. The exercise was assigned for treatment groups by a run on the treadmill as moderate intensity continuous (MIC), highintensity continuous (HIC), slow interval (SI), and fast interval (FI). The treatment groups were exercise throughout 8 weeks with a frequency of 3 times a week. RESULTS: The results showed that expression of PGC-1α gene was lower in all treatment groups compared to controls (p < 0.05). Expression in HIC was higher than MIC (p < 0.05), so was the expression in FI more than SI (p < 0.05). CONCLUSIONS: Exercise affected PGC-1α gene expression in the liver of the T2DM rat model. The expression of PGC-1α was linear with exercise intensity.

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Ginsenoside Re, Produces Multi-targeted Potent Antidiabetic Effects Via Estrogen Receptor Signaling Pathway in Rat, an Alternative Multi-Targeted Therapeutic for Type 2 Diabetes

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i54b33782 ◽

2021 ◽

pp. 216-236

Author(s):

Jingxian Gao ◽

Xianli Meng ◽

Bayin Zabu ◽

Yi Zhang ◽

Siqinbilig Wu ◽

...

Keyword(s):

Gene Expression ◽

Type 2 Diabetes ◽

Estrogen Receptor ◽

Signaling Pathway ◽

Rat Model ◽

B Cell Lymphoma ◽

Ginsenoside Re ◽

Antidiabetic Effects ◽

Targeted Therapeutic

Aims: To identify more effective ginsenoside for type 2 diabetes (T2D) and clarify whether the ginsenoside characterizing estrogenic multi-targeted antidiabetic effects. Study Design: Identifying more effective ginsenoside through preclinical evaluation of antidiabetic effects of representative ginsenosides with T2D rat model, and further test pharmacological mechanism underlying the potent antidiabetic effects of the ginsenoside in the same model. Place and Duration of Study: Key laboratory for Pharmacy, Inner Mongolia Medical University, March 2018 to November 2020. Methodology: Used a total of 240 female adult rats. Rat model of T2D induced by high-fat diet fed and streptozotocin. Five tapes of representative ginsenosides (Rb1, Rd, Rg3, Re, Rg1) administrated at low (20 mg/kg daily) and high (40 mg/ kg daily) doses to T2D rats with orally for 4 weeks. Detect testing indexes with biochemical, histological, Quantitative Real-Time PCR, and western blots analysis. Results: Ginsenoside Re (Re), very significantly lowered blood glucose (P<0.01), lipids (P<0.001), free fatty acid (P<0.001), and glucagon (P<0.01) levels, markedly improved impaired insulin sensitivity (P<0.01), ameliorated oxidative stress (P<0.01) and inflammation (P<0.01) in T2D rats, exhibited potent antidiabetic effects. Moreover, Re, phosphorylate serine/threonine kinase (Akt) (P<0.01) and endothelial nitric oxide synthase (eNOS) (P<0.01), up regulates B-cell lymphoma-2 (P<0.01) and insulin gene expression (P<0.01), down regulates glucagon gene expression(P<0.01), reverse impaired glucagon-like peptide 1 (P<0.01); exhibits multi-targeted effects; these effects of Re were inhibited by estrogen receptor (ER) inhibitor (ICI-182,780) (P<0.01). Functionally, the antidiabetic effects of Re were sequentially inhibited by inhibitor of ER, Akt, and eNOS, respectively (P<0.01). Conclusion: These findings, revealed a novel pharmacological property of Re that characterized in multi-targeted potent antidiabetic effects mediated by ER/Akt/eNOS/NO signaling pathway, provide the first evidence for the potential use of Re, as a multi-targeted therapeutic for T2D, particularly, a novel candidate for replacement of estrogen therapy and NO therapy in diabetes.

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The Expression of Liver Metabolic Enzymes AMPKα1, AMPKα2, and PGC-1α due to Exercise in Type-2 Diabetes Mellitus Rat Model

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2020.4550 ◽

2020 ◽

Vol 8 (A) ◽

pp. 629-632

Author(s):

Yetty Machrina ◽

Yunita Sari Pane ◽

Dharma Lindarto

Keyword(s):

Gene Expression ◽

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Rat Model ◽

High Intensity ◽

Metabolic Enzymes ◽

Moderate Intensity ◽

Metabolism Enzymes

BACKGROUND: AMP-activated protein kinase (AMPK) and PGC-1α were crucial metabolism enzymes not only in the skeletal muscles but also in the liver. Exercise can modify metabolic enzymes to improve insulin resistance. AIM: The aim of this study was to analyze the expression of mRNA liver metabolic enzymes gene, that is, AMPKα1, AMPKα2, and PGC-1α in different types and intensities of exercise. METHODS: Healthy male Wistar rats aged 8 weeks in 150–180 g body weight were given a combination of high fat diet for five weeks and low doses of streptozotocin (30 mg/kgbw and 45 mg/kgbw in 0.1 citrate buffer pH 4,5) to develop type 2 diabetes mellitus (T2DM) rat model. Animals then were divided into five groups: One group was sedentary, and four groups were forced to run on the treadmill 3 times/week, 30 min each season, for 8 weeks. mRNA gene expression of AMPKα1, AMPKα2, and PGC-1α was determined with real-time PCR. RESULTS: The results showed that expression of mRNA AMPKα1 in treatment groups was elevated than control and the much expression was showed in continuous types. The expression of mRNA AMPKα2 and PGC-1 α was declined in treatment group which little expression was showed in high intensity for AMPKα2 and moderate intensity for PGC-1 α. Base on type and exercise intensity, mRNA AMPKα1 gene expression much in moderate continuous, mRNA AMPKα2 gene expression higher in high intensity, both continuous and interval training, whereas mRNA PGC-1α gene expression higher in interval groups. CONCLUSION: Various types of aerobic exercises with moderate-vigorous intensities gave different impact to mRNA liver metabolic enzyme genes.

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Type 2 diabetes impairs tendon repair after injury in a rat model

Journal of Applied Physiology ◽

10.1152/japplphysiol.00767.2012 ◽

2012 ◽

Vol 113 (11) ◽

pp. 1784-1791 ◽

Cited By ~ 44

Author(s):

Aisha S. Ahmed ◽

Nikos Schizas ◽

Jian Li ◽

Mahmood Ahmed ◽

C.-G. Östenson ◽

...

Keyword(s):

Gene Expression ◽

Type 2 Diabetes ◽

Connective Tissue ◽

Achilles Tendon ◽

Rat Model ◽

Biomechanical Testing ◽

Collagen I ◽

Protein Distribution ◽

Altered Expression

Type 2 diabetes adversely affects the properties of native connective tissue. The underlying mechanisms, however, by which diabetes alters connective tissue metabolism, especially tendon, are poorly defined. The aim of this study was to determine the effect of type 2 diabetes on the mechanical, histological, and molecular properties of the intact and healing Achilles tendon. The right Achilles tendon was transected in 11 male diabetic Goto-Kakizaki (GK) and 10 age- and sex-matched Wistar control rats, while the left Achilles tendon was left intact. At 2 wk postinjury the intact and injured tendons were assessed by biomechanical testing and histology. The gene expression of collagen I and III, biglycan, versican, MMP-13, and MMP-3 was measured by quantitative RT-PCR, and their protein distribution was studied by immunohistochemistry. Intact tendons exhibited only small differences between the groups. In injured tendons, however, a significantly smaller transverse area and lower stiffness was found in diabetic GK compared with Wistar control rats. This correlated with impaired structural organization of collagen fibers and a reduced expression of collagen I and III in the injured tendons of the diabetic GK compared with Wistar control. Moreover, MMP-3 gene expression was downregulated in the injured diabetic GK tendons compared with injured Wistar controls. Our results indicate that in a rat model of diabetes tendon healing is impaired mainly due to altered expression of collagen and MMPs reflecting decreased degradation of matrix proteins and impaired tissue remodeling. Further our data suggest that therapeutic modulation of collagens or MMPs might be targets for new regenerative approaches in operated, injured, or maybe also degenerative tendon diseases in diabetes.

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