• Journal of Medicine and Life Science
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• 제20권3호
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• pp.126-130
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• 2023

Sodium-glucose cotransporter-2 (SGLT2) inhibitors have become increasingly prescribed because of their proven protective effects on the heart and kidneys, and carbohydrate-restricted diets are popular therapeutic approaches for patients with obesity and diabetes. A 28-year-old obese woman with recently diagnosed diabetes developed euglycemic diabetic ketoacidosis (DKA) while on dapagliflozin, an SGLT2 inhibitor, and following a carbohydrate-restricted diet. She presented with nausea, vomiting, and epigastric pain. Hospital tests showed a blood glucose of 172 mg/dL, metabolic acidosis, and increased ketone levels, confirming euglycemic DKA. Treatment involved discontinuing dapagliflozin and administering fluids, glucose, and insulin. She recovered and was discharged on the fourth day. This is considered a case of euglycemic DKA induced by SGLT2 inhibitors and triggered by a carbohydrate-restricted diet. This case highlights the importance of physicians in confirming the symptoms and laboratory results of DKA, even in patients with normal blood glucose levels taking SGLT2 inhibitors and following carbohydrate-restricted diets. It is also crucial to advise patients to maintain an adequate carbohydrate intake.

• 한국식생활문화학회지
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• 제24권2호
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• pp.219-223
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• 2009

We investigated the effect of Takju lees extract on blood glucose levels in the db/db mice (a murine model of type 2 diabetes mellitus). We fed 40 male db/db mice a control diet (G0, AIN93G) and experimental diets containing 1% (G1), 2% (G2), or 4% (G4) Takju lees extract for 4 weeks. We found no difference in food intake and body weight gain among the animal groups. In the G1 and G2 groups, plasma glucose levels decreased significantly between Days 10 and 21 compared with the G0 group. However, we found no difference in plasma glucose levels between groups G4 and G0. The change in insulin concentrations was not significant among these animal groups, and we found no significant difference in glucose transporter 4 (GLUT4) expression in the soleus muscle. These results suggest that the Takju lees extract has a beneficial effect in animals with type 2 diabetes.

• Nutrition Research and Practice
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• 제10권5호
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• pp.507-515
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• 2016

BACKGROUND/OBJECTIVES: This study was designed to investigate whether Gynura procumbens extract (GPE) can improve insulin sensitivity and suppress hepatic glucose production in an animal model of type 2 diabetes. MATERIALS/METHODS: C57BL/Ksj-db/db mice were divided into 3 groups, a regular diet (control), GPE, and rosiglitazone groups (0.005 g/100 g diet) and fed for 6 weeks. RESULTS: Mice supplemented with GPE showed significantly lower blood levels of glucose and glycosylated hemoglobin than diabetic control mice. Glucose and insulin tolerance test also showed the positive effect of GPE on increasing insulin sensitivity. The homeostatic index of insulin resistance was significantly lower in mice supplemented with GPE than in the diabetic control mice. In the skeletal muscle, the expression of phosphorylated AMP-activated protein kinase, pAkt substrate of 160 kDa, and PM-glucose transporter type 4 increased in mice supplemented with GPE when compared to that of the diabetic control mice. GPE also decreased the expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase in the liver. CONCLUSIONS: These findings demonstrate that GPE might improve insulin sensitivity and inhibit gluconeogenesis in the liver.

• 생약학회지
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• 제38권1호
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• pp.10-14
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• 2007

Type 2 diabetes mellitus relavant to insulin resistance is a chronic and hard to control. In order to develop an antidiabetic agent from natural products, anti-hyperglycemic effect of herbal formula containing Mori Follium, Euonymi Lignum Suberalatum and Ginseng Radix(MEG) was investigated in db/db mice. Treatment group was administered orally with MEG formula at a dose of 300 mg/kg for 5 weeks, and blood glucose, insulin and lipid levels were determined. MEG treatment group showed a marked decrease in fasting blood glucose level and insulin resistance index(IRI) compared to those in diabetic control. Improvement of insulin resistance(60.6%) was indicative of reducing lipid levels in plasma and triglyceride contents in muscle and adipose tissue. In addition, expressions of an insulin responsive gene, glucose transporter 4(Glut4), in muscle and adipose tissue were upregulated in MEG treatment group. Compared islet morphology between groups, MEG formula prevented the ${\beta}$-cell destruction caused by high blood glucose. Taken together, MEG formula can act as an anti-hyperglycemic agent with insulin sensitizing effect, and thus deserves a clinical trial in the future.

• Genomics & Informatics
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• 제12권4호
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• pp.240-246
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• 2014

Mutation in HNF1B, the hepatocyte nuclear factor-$1{\beta}$ (HNF-$1{\beta}$) gene, results in maturity-onset diabetes of the young (MODY) 5, which is characterized by gradual impairment of insulin secretion. However, the functional role of HNF-$1{\beta}$ in insulin secretion and glucose metabolism is not fully understood. We identified a family with early-onset diabetes that fulfilled the criteria of MODY. Sanger sequencing revealed that a heterozygous P159L (CCT to CTT in codon 159 in the DNA-binding domain) mutation in HNF1B was segregated according to the affected status. To investigate the functional consequences of this HNF1B mutation, we generated a P159L HNF1B construct. The wild-type and mutant HNF1B constructs were transfected into COS-7 cells in the presence of the promoter sequence of human glucose transporter type 2 (GLUT2). The luciferase reporter assay revealed that P159L HNF1B had decreased transcriptional activity compared to wild-type (p < 0.05). Electrophoretic mobility shift assay showed reduced DNA binding activity of P159L HNF1B. In the MIN6 pancreatic ${\beta}$-cell line, overexpression of the P159L mutant was significantly associated with decreased mRNA levels of GLUT2 compared to wild-type (p < 0.05). However, INS expression was not different between the wild-type and mutant HNF1B constructs. These findings suggests that the impaired insulin secretion in this family with the P159L HNF1B mutation may be related to altered GLUT2 expression in ${\beta}$-cells rather than decreased insulin gene expression. In conclusion, we have identified a Korean family with an HNF1B mutation and characterized its effect on the pathogenesis of diabetes.

• 한국임상약학회지
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• 제27권4호
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• pp.214-220
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• 2017

Background: Dapagliflozin is an oral selective inhibitor of sodium-glucose cotransporter 2(SGLT2), the kidney transporter chiefly responsible for glucose reabsorption from the glomerular filtrate. Because this mechanism does not require the action of insulin, dapagliflozin rarely causes hypoglycemia. Dapagliflozin may affect blood glucose control as well as blood pressure and the body weight which are one of the cardiovascular disease risk factors. However, dehydration and ketoacidosis are reported as the side effects of the dapagliflozin treatment and the safety issues have been occurred. The aim of this study is to analyze the effectiveness and adverse events of dapagliflozin in Korean patients. Methods: From December 2014 to August 2015, we retrospectively reviewed the electronic medical records of type 2 diabetes patients who were prescribed dapagliflozin at Severance Hospital. Results: A total of 202 Korean patients were enrolled in this study. The effectiveness in the reduction of blood glucose was statistically significant(p<0.001). Dapagliflozin decreased 0.74% of HbA1c after 24 weeks. Significantly more participants achieved the target HbA1c level(HbA1c<7%) after 24 weeks(n=42, 35.3%) than before taking dapagliflozin(n=21, 17.6%). Blood pressure decreased 5.7 mmHg systolic blood pressure(SBP), 1.9 mmHg diastolic blood pressure(DBP) after 24 weeks. More than one quarter of participants(n=35, 29.4%) experienced weight loss. Most common adverse event was genitourinary symptoms. Conclusion: In this study, the effectiveness of dapagliflozin in improving glycemic control, blood pressure control, and weight loss was statistically significant. However, elderly and female patients, who have higher incidence of adverse events, should use dapagliflozin cautiously.

• 대한수의학회지
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• 제37권2호
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• pp.301-310
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• 1997

Diabetes mellitus is associated with a wide range of pathophysiological in the kidney. This study was designed to examine the effects of high glucose concentration on IGF-I binding and glucose transporters in renal proximal tubule cells. The results were as follows : The binding of $^{125}I-IGF-I$ reached the peak at the 30 minutes and gradually decreased by the time dependent manner. The binding of $^{125}I-IGF-I$ was inhibited by the unlabelled IGF-I($10^{-14}{\sim}10^{-8}M$) in a concentration dependent manner. The relative affinity of IGF-I receptor for IGF-I, IGF-II and insulin exhibited typical type 1 binding(IGF-I > insulin > IGF-II). However IGF-II did not compete for the cultured cell membrane $^{125}I-IGF-I$ binding site at $10^{-14}{\sim}10^{-8}M$. Under optimal conditions, IGF-I binding to the membranes from 5mM and 20mM glucose treated cells was analyzed. It was found that 20mM glucose treated cells exhibited higher binding activity for IGF-I. In order to further substantiate this increase in IGF-I binding sites, we performed affinity-labelling studies. The cross-linked cell membrane subjected to SDS-PAGE; labelled material was detected by autoradiography. 20mM glucose treated cells exhibited higher levels. The initial rate of $methyl-{\alpha}-D-glucopyranoside({\alpha}-MG)$ uptake was significantly lower($74.41{\pm}6.71%$) in monolayers treated with 20mM glucose than those of 5mM glucose. However, 3-O-methyl-D-glucose(3-O-MG) uptake was not affected by glucose concentration in culture media. IGF-I significantly increased ${\alpha}-MG$ uptake in both 5mM and 20mM glucose treated cells. However, 3-O-MG uptake was not affected by IGF-I in both conditions. In conclusion, 20mM glucose increased binding sites of $^{125}I-IGF-I$, inhibited Na/glucose cotransporter activity. But 20mM glucose did not change facilitated glucose transporter.

• Asian Pacific Journal of Cancer Prevention
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• 제17권1호
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• pp.147-151
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• 2016

Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity and some of these have been documented in association or preceded by oral epithelial dysplasia (OED). Aggressive cancers with fast growth have demonstrated overexpression of some glucose transporters (GLUTs). Thus, the aim of this study was to analyze the immunohistochemical expression of the glucose transporter, GLUT-1, in OEDs and OSCCs, seeking to better elucidate the biological behavior of neoplasias. Fifteen cases were selected this research of both lesions. Five areas were analyzed from each case by counting the percentage of positive cells at 400x magnification. Immunoreactivity of GLUT-1 was observed in 100% of the samples ranging from 54.2% to 86.2% for the OSCC and 73.9% to 97.4% for the OED. Statistical test revealed that there was greater overexpression of GLUT-1 in OED than the OSCC (p=0.01). It is believed the high expression of GLUT-1 may reflect the involvement of GLUT-1 in early stages of oral carcinogenesis.

• 대한의생명과학회지
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• 제12권1호
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• pp.17-22
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• 2006

The baculovirus expression system is a powerful method for producing large amounts of the human erythrocyte-type glucose transport protein, heterologously. Characterization of the expressed protein is expected to show its ability to transport sugars directly. To achieve this, it is a prerequisite to know the properties of the endogenous sugar transport system in Spodoptera frugiperda Clone 21 (Sf21) cells, which are commonly employed as a host permissive cell line to support the baculovirus replication. The Sf21 cells can grow well on TC-100 medium that contains 0.1% D-glucose as the major carbon source, strongly suggesting the presence of endogenous glucose transport system. However, unlike the human glucose transport protein that has a broad substrate and inhibitor specificity, very little is known about the nature of the endogenous sugar transport system in Sf21 cells. In order to characterize further the inhibitor recognition properties of the Sf21 cell transporter, the ability of phloretin, cytochalasin B and D-fructose to inhibit 2-deoxy-D-glucose (2dGlc) transport was examined by measuring inhibition constants $(K_i)$. The $K_i's$ for reversible inhibitors were determined from plots of uptake versus inhibitor concentration. The 2dGlc transport in the Sf21 cells was very potently inhibited by phloretin, the aglucone of phlorizin with a $K_i$ similar to the value of about $2{\mu}M$ reported for inhibition of glucose transport in human erythrocytes. However, the Sf21 cell transport system was found to differ from the human transport protein in being much less sensitive to inhibition by cytochalasin B (apparent $K_i$ approximately $10\;{\mu}M$). In contrast, It is reported that the inhibitor binds the human erythrocyte counterpart with a $K_d$ of approximately $0.12\;{\mu}M$. Interestingly, the Sf21 glucose transport system also appeared to have high affinity for D-fructose with a $K_i$ of approximately 5mM, contrasting the reported $K_m$ of the human erythrocyte transport protein for the ketose of 1.5M.

• Journal of Nutrition and Health
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• 제55권1호
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• pp.70-84
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• 2022

Purpose: Skeletal muscles display significant heterogeneity in metabolic responses, owing to the composition of metabolically distinct fiber types. Recently, numerous studies have reported that in skeletal muscles, suppression of genes related to fatty acid channeling alters the triacylglycerol (TAG) synthesis and switches the energy substrates. However, such responses may differ, depending on the type of muscle fiber. Hence, we conducted in vitro and animal studies to compare the metabolic responses of different types of skeletal muscle fibers to the deficiency of fatty acyl-CoA synthetase (Acsl)6, one of the main fatty acid-activating enzymes. Methods: Differentiated skeletal myotubes were transfected with selected Acsl6 short interfering RNA (siRNA), and C57BL/6J mice were subjected to siRNA to induce Acsl6 deficiency. TAG accumulation and expression levels of insulin signaling proteins in response to acute glucose supplementation were measured in immortalized cell-based skeletal myotubes, oxidative muscles (OM), and glycolytic muscles (GM) derived from the animals. Results: Under conditions of high glucose supplementation, suppression of the Acsl6 gene resulted in decreased TAG and glycogen synthesis in the C2C12 skeletal myotubes. The expression of Glut4, a glucose transporter, was similarly downregulated. In the animal study, the level of TAG accumulation in OM was higher than levels determined in GM. However, a similar decrease in TAG accumulation was obtained in the two muscle types in response to Acsl6 suppression. Moreover, Acsl6 suppression enhanced the phosphorylation of insulin signaling proteins (Foxo-1, mTORc-1) only in GM, while no such changes were observed in OM. In addition, the induction ratio of phosphorylated proteins in response to glucose or Acsl6 suppression was significantly higher in GM than in OM. Conclusion: The results of this study demonstrate that Acsl6 differentially regulates the energy metabolism of skeletal muscles in response to glucose supplementation, thereby indicating that the fiber type or fiber composition of mixed muscles may skew the results of metabolic studies.