• 약학회지
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• 제56권6호
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• pp.364-365
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• 2012

Liver is the major organ to regulate the systemic glucose homeostasis and insulin resistance. Excess energy intake leads to triglyceride accumulation in adipose tissue first and subsequent accumulation in liver, resulting in obesity and type 2 diabetes. The representative pathological animal model for obesity associated insulin resistance is a high fat diet (HFD) fed mice model. Given the essential role of liver fat accumulation in developing systemic insulin resistance in obesity, I measured the liver triglyceride contents in HFD fed mice as a function of time. As such, in this report, I show the cause and effect relationship with regard to time during a HFD feeding between a variety of factors that are related to systemic insulin resistance including glucose intolerance, plasma insulin level and inflammatory gene expression in liver and adipose tissue.

• Korean Circulation Journal
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• 제48권11호
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• pp.951-963
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• 2018

HMG-CoA reductase inhibitors, i.e. statins, are effective in reducing cardiovascular disease events but also in cardiac-related and overall mortality. Statins are in general well-tolerated, but currently the concerns are raised if statins may increase the risk of new-onset diabetes mellitus (NOD). In this review, the possible effects of statins on organs/tissues being involved in glucose metabolism, i.e. liver, pancreas, adipose tissue, and muscles, had been discussed. The net outcome seems to be inconsistent and often contradictory, which may be largely affected by in vitro experimental settings or/and in vivo animal conditions. The majority of studies point out statin-induced changes of regulations of isoprenoid metabolites and cellassociated cholesterol contents as predisposing factors related to the statin-induced NOD. On the other hand, it should be considered that dysfunctions of isoprenoid pathway and mitochondrial ATP production and the cholesterol homeostasis are already developed under (pre)diabetic and hypercholesterolemic conditions. In order to connect the basic findings with the clinical manifestation more clearly, further research efforts are needed.

• BMB Reports
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• 제45권9호
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• pp.489-495
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• 2012

Ischemia is a blockage of blood supply due to an embolism or a hemorrhage in a blood vessel. When an organ cannot receive oxygenated blood and can therefore no longer replenish its blood supply due to ischemia, stresses, such as the disruption of blood glucose homeostasis, hypoglycemia and hypoxia, activate the AMPK complex. LKB1 and $CaMKK{\beta}$ are essential activators of the AMPK signaling pathway. AMPK triggers proangiogenic effects through the eNOS protein in tissues with ischemic conditions, where cells are vulnerable to apoptosis, autophagy and necrosis. The AMPK complex acts to restore blood glucose levels and ATP levels back to homeostasis. This review will discuss AMPK, as well as its key activators (LKB1 and $CaMKK{\beta}$), as a central energy regulator and evaluate the upstream and downstream regulating pathways of AMPK. We will also discuss how we can control this important enzyme in ischemic conditions to prevent harmful effects in patients with vascular damage.

• BMB Reports
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• 제51권4호
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• pp.200-205
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• 2018

Exercise and resveratrol supplementation exhibit anti-obesity functions in the long term but have not been fully investigated yet in terms of their early potential effectiveness. Mice fed with high-fat diet were categorized into control (Cont), exercise (Ex), resveratrol supplementation (Res), and exercise combined with resveratrol supplementation (Ex + Res) groups. In the four-week period of weight loss, exercise combined with resveratrol supplementation exerted no additional effects on body weight loss but significantly improved whole-body glucose and lipid homeostasis. The combined treatment significantly decreased intrahepatic lipid content but did not affect intramyocellular lipid content. Moreover, the treatment significantly increased the contents of mtDNA and cytochrome c, the expression levels of peroxisome proliferator-activated receptor gamma coactivator-1 alpha and its downstream transcription factors, and the activities of ATPase and citrate synthase. However, exercise, resveratrol, and their combination did not promote myofiber specification toward slow-twitch type. The effects of exercise combined with resveratrol supplementation on weight loss could be partly due to enhanced mitochondrial biogenesis and not to fiber-type shift in skeletal muscle tissues.

• BMB Reports
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• 제57권9호
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• pp.417-423
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• 2024

Glucose-dependent insulinotropic polypeptide (GIP), a 42-amino-acid hormone, exerts multifaceted effects in physiology, most notably in metabolism, obesity, and inflammation. Its significance extends to neuroprotection, promoting neuronal proliferation, maintaining physiological homeostasis, and inhibiting cell death, all of which play a crucial role in the context of neurodegenerative diseases. Through intricate signaling pathways involving its cognate receptor (GIPR), a member of the G protein-coupled receptors, GIP maintains cellular homeostasis and regulates a defense system against ferroptosis, an essential process in aging. Our study, utilizing GIP-overexpressing mice and in vitro cell model, elucidates the pivotal role of GIP in preserving neuronal integrity and combating age-related damage, primarily through the Epac/Rap1 pathway. These findings shed light on the potential of GIP as a therapeutic target for the pathogenesis of ferroptosis in neurodegenerative diseases and aging.

• Preventive Nutrition and Food Science
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• 제22권3호
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• pp.172-183
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• 2017

Vitamin A and its metabolites modulate insulin resistance and regulate stearoyl-CoA desaturase 1 (SCD1), which are also known to affect insulin resistance. Here, we tested, whether vitamin A-mediated changes in insulin resistance markers are associated with SCD1 regulation or not. For this purpose, 30-week old male lean and glucose-intolerant obese rats of WNIN/GR-Ob strain were given either a stock or vitamin A-enriched diet, i.e. 2.6 mg or 129 mg vitamin A/kg diet, for 14 weeks. Compared to the stock diet, vitamin A-enriched diet feeding improved hyperglycemia and glucose-clearance rate in obese rats and no such changes were seen in lean rats receiving identical diets. These changes were corroborated with concomitant increase in circulatory insulin and glycogen levels of liver and muscle (whose insulin signaling pathway genes were up-regulated) in obese rats. Further, the observed increase in muscle glycogen content in these obese rats could be explained by increased levels of the active form of glycogen synthase, the key regulator of glycogen synthesis pathway, possibly inactivated through increased phosphorylation of its upstream inhibitor, glycogen synthase kinase. However, the unaltered hepatic SCD1 protein expression (despite decreased mRNA level) and increased muscle-SCD1 expression (both at gene and protein levels) suggest that vitamin A-mediated changes on glucose metabolism are not associated with SCD1 regulation. Chronic consumption of vitamin A-enriched diet improved hyperglycemia and glucose-intolerance, possibly, through the regulation of intracellular signaling and glycogen synthesis pathways of muscle and liver, but not associated with SCD1.

• Clinical and Experimental Pediatrics
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• 제63권3호
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• pp.110-114
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• 2020

Background: Subclinical hypothyroidism (SH) is a common condition in obese children. However, its effect on glucose and lipid metabolism in obese children remains controversial. Purpose: The present study aimed to investigate the association between SH and metabolic parameters. Methods: A total of 215 obese children and adolescents aged 6-18 years were included in this retrospective cross-sectional study. The patients' anthropometric measurements such as thyrotropin (TSH), free thyroxine (fT4), fasting plasma glucose, and insulin levels, as well as homeostasis model assessment for insulin resistance (HOMA-IR) index, and lipid profiles were evaluated. The patients were allocated to the SH group (fT4 normal, TSH 5-10 mIU/L) (n=77) or the control group (fT4 normal, TSH<5 mIU/L) (n=138). The glucose and lipid metabolisms of the 2 groups were compared. Results: SH was identified in 77 of 215 patients (36%). Mean body mass index was similar in both groups. The mean serum insulin, HOMA-IR, and triglyceride (TG) levels were higher and the mean high-density lipoprotein cholesterol level was lower in the SH group than in the control group (P=0.007, P=0.004, P=0.01, and P=0.02, respectively). A positive correlation was observed between TSH level and insulin level, HOMA-IR, and TG level. Conclusion: SH was identified in some of the obese children and adolescents. A clear association was observed between SH, insulin resistance, and dyslipidemia in obese children.

• Asian Pacific Journal of Cancer Prevention
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• 제16권18호
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• pp.8053-8058
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• 2016

Metformin is known as a hypoglycaemic agent that regulates glucose homeostasis by inhibiting liver glucose production and increasing muscle glucose uptake. Colorectal cancer (CRC) is one of the most common cancers worldwide, with about a million new cases diagnosed each year. The risk factors for CRC include advanced age, smoking, black race, obesity, low fibre diet, insulin resistance, and the metabolic syndrome. We have searched Medline for the metabolic syndrome and its relation to CRC, and metformin as a potential treatment of colorectal cancer. Administration of metformin alone or in combination with chemotherapy has been shown to suppress CRC. The mechanism that explains how insulin resistance is associated with CRC is complex and not fully understood. In this review we have summarised studies which showed an association with the metabolic syndrome as well as studies which tackled metformin as a potential treatment of CRC. In addition, we have also provided a summary of how metformin at the cellular level can induce changes that suppress the activity of cancer cells.

• Archives of Pharmacal Research
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• 제29권3호
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• pp.256-264
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• 2006

Salicornia herbacea L. (Chenopodiaceae) has been used as a seasoned vegetable by living in coastal areas. S. herbacea (SH) has been demonstrated to stimulate cytokine production, nitric oxide release, and to show anti-oxidative effect. In a series of investigations to develop potential anti-diabetic and/or anti-hyperlipidemic agents from Korean indigenous plants, 50% ethanol extract of Salicornia herbacea was found to prevent the onset of the hyperglycemia and hyperlipidemia induced by high fat diet in ICR mice. At 6 week old, the ICR mice were randomly divided into five groups; two control and three treatment groups. The control mice were to receive either a regular diet (RD) or high-fat diet (HFD), and the treatment groups were fed a high fat diet with either 350 mg/kg, 700 mg/kg of SH (SH350 and SH700) or 250 mg/kg of met-formin (MT250) for a 10-week period. SH not only reduced body weight but also corrected associated hyperglycemia and hyperlipidemia in a dose dependent manner. SH exerted beneficial effects on the plasma glucose and lipid homeostasis possibly ascribed to its specific effects on lipogenesis related genes (SREBP1a, FAS, GAPT), and PEPCK, glucose 6-phosphatase gene expressions in liver. Ethanol extract of S. herbacea has potential as a preventive agent for type 2 diabetes (and possibly hyperlipidemia) and deserves future clinical trial.

• Korean Circulation Journal
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• 제53권1호
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• pp.34-46
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• 2023

Background and Objectives: Diabetes mellitus (DM)-associated heart failure (HF) causes high morbidity and mortality. In this study, we established a zebrafish larvae model for in vivo research on diabetic HF. Methods: DM-like phenotypes were induced by treating zebrafish larvae with a combination of D-glucose (GLU) and streptozotocin (STZ). HF was induced by treatment with terfenadine (TER), a potassium channel blocker. Additionally, myocardial contractility, motility, and viability were evaluated. Results: The zebrafish larvae treated with a combination of GLU and STZ showed significantly higher whole-body glucose concentrations, lower insulin levels, and higher phosphoenolpyruvate carboxykinase levels, which are markers of abnormal glucose homeostasis, than the group treated with only GLU, with no effect on viability. When treated with TER, DM zebrafish showed significantly less myocardial fractional shortening and more irregular contractions than the non-DM zebrafish. Furthermore, in DM-HF with reduced ejection fraction (rEF) zebrafish, a significant increase in the levels of natriuretic peptide B, a HF biomarker, markedly reduced motility, and reduced survival rates were observed. Conclusions: We established a DM-HFrEF zebrafish model by sequentially treating zebrafish larvae with GLU, STZ, and TER. Our findings indicate the potential utility of the developed zebrafish larvae model not only in screening studies of new drug candidates for DM-HFrEF but also in mechanistic studies to understand the pathophysiology of DM-HFrEF.