• Journal of Korean Neurosurgical Society
• /
• v.42 no.6
• /
• pp.470-474
• /
• 2007

Objective : The brain is dependent on glucose as an energy source. Intricate homeostatic mechanisms have been implicated in maintaining the blood glucose concentration in the brain. The aim of this study is to find the way to identify the metabolic proteins regulating the glucose in rat hypothalamus. Methods : In this study, we analysed the secretome from rat hypothalamus in vivo. We introduced 500 nM of insulin into the rat hypothalamus. The chromatographic patterns of the secretome were identified, after which Mass Spectrometry-Mass Spectrometry (MS-MS) analysis was performed. Results : In Liquid Chromatography-Mass Spectrometry (LC-MS) analysis, 60 proteins were identified in the secretome. Among them, 8 novel proteins were unveiled and were associated with the energy metabolism of insulin signaling in mitochondria of rat hypothalamic neuron. Nineteen other proteins have unknown functions. These ligands were confirmed to be secreting from the rat hypothalmus on insulin signaling by western blotting. Conclusion : The hypothalamus is the master endocrine gland responsible for the regulation of various physiological and metabolic processes. Proteomics using LC-MS analysis offer a efficient means for generating a comprehensive analysis of hypothalamic protein expression by insulin signaling.

• Molecules and Cells
• /
• v.38 no.4
• /
• pp.297-303
• /
• 2015

Skeletal muscle insulin resistance, which increases the risk for developing various metabolic diseases, including type 2 diabetes, is a common metabolic disorder in obesity and aging. If potential treatments are to be developed to treat insulin resistance, then it is important to fully understand insulin signaling and glucose metabolism. While recent large-scale "omics" studies have revealed the acetylome to be comparable in size to the phosphorylome, the acetylation of insulin signaling proteins and its functional relevance to insulin-stimulated glucose transport and glucose metabolism is not fully understood. In this Mini Review we discuss the acetylation status of proteins involved in the insulin signaling pathway and review their potential effect on, and relevance to, insulin action in skeletal muscle.

• Diabetes and Metabolism Journal
• /
• v.42 no.6
• /
• pp.465-471
• /
• 2018

My professional journey to understand the glucose homeostasis began in the 1990s, starting from cloning of the promoter region of glucose transporter type 2 (GLUT2) gene that led us to establish research foundation of my group. When I was a graduate student, I simply thought that hyperglycemia, a typical clinical manifestation of type 2 diabetes mellitus (T2DM), could be caused by a defect in the glucose transport system in the body. Thus, if a molecular mechanism controlling glucose transport system could be understood, treatment of T2DM could be possible. In the early 70s, hyperglycemia was thought to develop primarily due to a defect in the muscle and adipose tissue; thus, muscle/adipose tissue type glucose transporter (GLUT4) became a major research interest in the diabetology. However, glucose utilization occurs not only in muscle/adipose tissue but also in liver and brain. Thus, I was interested in the hepatic glucose transport system, where glucose storage and release are the most actively occurring.

• Journal of Veterinary Clinics
• /
• v.31 no.3
• /
• pp.163-169
• /
• 2014

Glucose metabolism abnormalities secondary to heart failure, including insulin resistance (IR) and impaired fasting glucose, have been gradually recognized as important prognostic factors in disease progression. However, to date, no study has investigated glucose abnormalities in dogs with chronic mitral valve insufficiency (CMVD). Thus, we hypothesized that glucose metabolism abnormalities due to heart failure may develop in dogs with CMVD. A prospective study was performed on 113 client-owned dogs with variable CMVD severities. Serum insulin, glucagon, fructosamine, and glucose concentrations were measured, and insulin resistance was determined using the homeostatic model assessment (HOMA) score. The serum insulin concentration had a significant inverse association with the heart failure severity. However, there was no significant association between the heart failure severity and fructosamine, HOMA score, and fasting blood glucose. Insulin, fructosamine, and HOMA had a significant positive association with body condition scores (BCS), whereas glucose had no association. This study found that insulin secretion in dogs with naturally occurring heart failure due to CMVD might be compromised as the disease worsens.

• Biomolecules & Therapeutics
• /
• v.12 no.4
• /
• pp.228-234
• /
• 2004

Brazilin shows hypoglycemic effect in diabetic animals through enhancement of glucose metabolisms in insulin responsive tissues. One of the major mechanisms of brazilin to enhance glucose metabolism is stimulation of glucose transport in adipocytes. In this study, the essential molecular moiety of brazilin for the stimulation of glucose transport was investigated. We found that brazilin undergoes a structural change in physiological buffer and produces hydrogen peroxide. Methylation of hydroxyl group of brazilin or addition of catalase along with brazilin resulted in the complete inhibition of brazilin-induced glucose transport in adipocytes. Because hydrogen peroxide increases glucose transport by inhibition of phosphatases, we examined the effect of brazilin on phosphatase activity. Brazilin inhibited phosphatases in a wide range of activity, and protein phosphatase 1 and 2A were also inhibited. These results suggest that the production of hydrogen peroxide by oxidation of catechol hydroxyl group of brazilin mediates glucose transport through inhibition of phosphatases which otherwise decrease glucose transport in adipocytes.

• Journal of Neurocritical Care
• /
• v.11 no.2
• /
• pp.81-85
• /
• 2018

Proper glucose management in hospitalized patients can improve clinical outcomes. In particular, intensive care unit (ICU) patients are known to have significantly higher rates of mortality from changes in blood glucose due to severe comorbidities. Improving glucose control in ICU patients, therefore, can improve mortality and prognosis. Several studies related to the management of blood glucose in the ICU patients have been conducted. Intensive glucose management of surgical ICU patients has been successful. However, studies on medical ICU patients did not demonstrate positive effects of strict glycemic control. There is no independent glucose management goal for neurological ICU patients. However, maintenance of the usual glucose control target of 140-180 mg/dL is recommended for ICU patients. Intravenous insulin infusion is essential for glucose control in ICU patients not consuming a regular diet, and caution should be exercised to prevent hypoglycemia.

• Biomolecules & Therapeutics
• /
• v.26 no.1
• /
• pp.4-9
• /
• 2018

Cancer metabolism as a field of research was founded almost 100 years ago by Otto Warburg, who described the propensity for cancers to convert glucose to lactate despite the presence of oxygen, which in yeast diminishes glycolytic metabolism known as the Pasteur effect. In the past 20 years, the resurgence of interest in cancer metabolism provided significant insights into processes involved in maintenance metabolism of non-proliferating cells and proliferative metabolism, which is regulated by proto-oncogenes and tumor suppressors in normal proliferating cells. In cancer cells, depending on the driving oncogenic event, metabolism is re-wired for nutrient import, redox homeostasis, protein quality control, and biosynthesis to support cell growth and division. In general, resting cells rely on oxidative metabolism, while proliferating cells rewire metabolism toward glycolysis, which favors many biosynthetic pathways for proliferation. Oncogenes such as MYC, BRAF, KRAS, and PI3K have been documented to rewire metabolism in favor of proliferation. These cell intrinsic mechanisms, however, are insufficient to drive tumorigenesis because immune surveillance continuously seeks to destroy neo-antigenic tumor cells. In this regard, evasion of cancer cells from immunity involves checkpoints that blunt cytotoxic T cells, which are also attenuated by the metabolic tumor microenvironment, which is rich in immuno-modulating metabolites such as lactate, 2-hydroxyglutarate, kynurenine, and the proton (low pH). As such, a full understanding of tumor metabolism requires an appreciation of the convergence of cancer cell intrinsic metabolism and that of the tumor microenvironment including stromal and immune cells.

• Biomolecules & Therapeutics
• /
• v.11 no.2
• /
• pp.81-84
• /
• 2003

Recently, diabetes has been found to be associated with osteoporosis. Specially in IDDM. In both type I and type II diabetes, glucose levels are elevated. Thus, a linkage between high glucose and osteoporosis can not be ruled out. In this study, an attempt has been made to observe the effect of high glucose on bone formation; osteoblast like UMR 106 cells were treated with high glucose (22 mM, 33 mM) for 1, 3 or 7 days. The high concentration of glucose inhibited markers. of bone formation activity such as alkaline phosphatase and collagen synthesis. In addition, reduction in the level of total cellular protein in response to high glucose was also observed. This study showed high glucose concentration could alter the bone metabolism leading to a defective bone formation and thus paving the linkage of such situation to diabetic complications.

• Microbiology and Biotechnology Letters
• /
• v.46 no.1
• /
• pp.29-39
• /
• 2018

Vibrio vulnificus needs various responsive mechanisms to survive and transmit successfully in alternative niches of human and marine environments, and to ensure the acquisition of steady energy supply to facilitate such unique life style. The bacterium had genetic constitution very different from that of Escherichia coli regarding metabolism of glycogen, a major energy reserve. V. vulnificus accumulated more glycogen than other bacteria and at various levels according to culture medium and carbon source supplied in excess. Glycogen was accumulated to the highest level in Luria-Bertani (3.08 mg/mg protein) and heart infusion (4.30 mg/mg protein) complex media supplemented with 1% (w/v) maltodextrin at 3 h into the stationary phase. Regarding effect of carbon source, more glycogen was accumulated when maltodextrin (2.34 mg/mg protein) was added than when glucose or maltose (0.78.1-14 mg/mg protein) was added as an excessive carbon source to M9 minimal medium, suggesting that maltodextrin metabolism might affect glycogen metabolism very closely. These results were supported by the analysis using the malP (encoding a maltodextrin phosphorylase) and malQ (encoding a 4-${\alpha}$-glucanotransferase) mutants, which accumulated much less glycogen than wild type when either glucose or maltodextrin was supplied as an excessive carbon source, but at different levels (3.1-80.3% of wild type glycogen). Therefore, multiple pathways for glycogen metabolism were likely to function in V. vulnificus and that responding to maltodextrin might be more efficient in synthesizing glycogen. All of the glycogen samples from 3 V. vulnificus strains under various conditions showed a narrow side chain length distribution with short chains (G4-G6) as major ones. Not only the comparatively large accumulation volume but also the structure of glycogen in V. vulnificus, compared to other bacteria, may explain durability of the bacterium in external environment.

• Asian-Australasian Journal of Animal Sciences
• /
• v.17 no.8
• /
• pp.1062-1068
• /
• 2004

Leptin has a major role in the regulation of food intake and energy homeostasis. In addition, leptin participates in many physiological functions including regulation of lipid metabolism. Bovine recombinant leptin protein was produced in E. coli cells in order to understand function of leptin in the regulation of lipid metabolism. The leptin expression vector was constructed in pGEX-4T-3 vector and transformed into E. coli BL21 cells. Expression of the GST-leptin fusion protein was induced with IPTG. The fusion protein was purified using glutathione sepharose 4B batch method, and the recombinant leptin was eluted after thrombin protease digestion. The effect of leptin on glucose transport was examined in the differentiated adipocytes of 3T3-L1 cells. Leptin had no effect on basal and insulin-stimulated glucose transport in 3T3-L1 cells (p>0.05). Effect of recombinant leptin on glucose and acetate transport was examined in adipose tissues of Korean cattle (Hanwoo). Insulin stimulated glucose transport in both intramuscular and subcutaneous adipose tissues (p<0.05), but leptin did not affect glucose transport in both adipose tissues (p>0.05). Insulin stimulated acetate transport in bovine adipose tissues (p<0.05), but leptin did not affect acetate transport (p>0.05). Northern and RT-PCR analyses showed that mRNA levels of uncoupling protein-2 were increased by leptin treatment in 3T3-L1 cells without statistical difference (p>0.05). In conclusion, bovine recombinant leptin did not affect glucose and acetate transport in both 3T3-L1 adipocytes and bovine adipose tissues, while it stimulates UCP-2 mRNA expression in 3T3-L1 cells.