Diabetes & Metabolism Journal

Volume 29(1); January 2005

Review

The Role of AMPK in Vascular Endothelium.: Woo Je Lee, Jin Yob Kim, Eun Hee Koh, Sung Min Han, Min Seon Kim, Ki Up Lee, Joong Yeol Park; Korean Diabetes J. 2005;29(1):1-5. Published online January 1, 2005

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Abstract PDF: No abstract available.

Original Articles

AMPK Activator AICAR Inhibits Hepatic Gluconeogenesis and Fatty Acid Oxidation.: Jin Yob Kim, Eun Hee Koh, Woo Je Lee, Seong Min Han, Ji Young Youn, Hye Sun Park, Hyun Sik Kim, Min Seon Kim, Joong Yeol Park, Ki Up Lee; Korean Diabetes J. 2005;29(1):6-14. Published online January 1, 2005

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Abstract PDF: BACKGROUND
Recent studies have demonstrated that adiponectin and metformin activate AMPK in the liver, and adiponectin and metformin stimulate fatty acid oxidation while inhibiting glucose production in liver. These results are in contrast to previous studies that have demonstrated that increased fatty acid oxidation in the liver is associated with increased gluconeogenesis. The present study was undertaken to reinvestigate the effects of AMPK activation by AICAR on hepatic fatty acid oxidation and gluconeogenesis. METHODS: HePG2 cells were treated with various concentrations of AICAR, and then the fatty acid oxidation and gluconeogenesis of the cells were determined. To investigate the in vivo effect of AICAR, Sprague-Dawely rats were infused with AICAR (bolus, 40 mg/g; constant, 7.5 mg/g/min-1) for 90min. RESULTS: Incubation of the HePG2 cells with higher concentrations (=1 mM) of AICAR increased fatty acid oxidation and gluconeogenesis. On the other hand, incubation of HePG2 cells with lower concentrations (0.05 and 0.1 mM) of AICAR decreased fatty acid oxidation and gluconeogenesis. Consistent with this in vitro data, the intravenous administration of AICAR to rats lowered their plasma glucose concentration and inhibited hepatic gluconeogenesis. Fatty acid oxidation in the liver tissue was significantly decreased by the administration of AICAR. CONCLUSION: The present study has demonstrated that AICAR decreased gluconeo-genesis in the liver. In contrast to previous studies, AICAR profoundly decreased hepatic fatty acid oxidation in rats and also in cultured hepatocytes

Increase in Fatty Acid Oxidation by AICAR: the Role of p38 MAPK.: Woo Je Lee, Jin Yob Kim, Sung Jin Bae, Eun Hee Koh, Sung Min Han, Hye Sun Park, Hyun Sik Kim, Min Seon Kim, Joong Yeol Park, Ki Up Lee; Korean Diabetes J. 2005;29(1):15-21. Published online January 1, 2005

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Abstract PDF: BACKGROUND
AMPK is an enzyme that increases glucose transport and fatty acid oxidation in skeletal muscle. The activation of AMPK stimulates fatty acid oxidation by decreasing the acetyl CoA carboxylase (ACC) activity and the concentration of malonyl-CoA. However, a recent study has reported a dissociation of AMPK activity and ACC phosphorylation in skeletal muscle during periods of prolonged exercise. This suggested that there is an additional mechanism for AMPK-induced fatty acid oxidation in skeletal muscle. METHODS: Plamitate oxidation was measured via the generation of [3H]-water generation from 9,10[3H]-palmitate after treating various concentrations of AICAR on the C2C12 mouse skeletal muscle cell line. Western analysis was used to test for the possible activation of p38 MAPK by AICAR. Involvement of p38 MAPK in the AICAR-induced increase in fatty acid oxidation was tested for by using SB203580, a p38 MAPK inhibitor. RESULTS: C2C12 cell treated with AICAR exhibited a dose-dependent increase in fatty acid oxidation compared to the cells that were not treated with AICAR. Western blot analysis revealed that phosphorylation of p38 MAPK was increased 2.5 folds after AICAR treatment. The increase of fatty acid oxidation with AICAR treatment was significantly inhibited by a treatment of SB203580; this indicated the involvement of p38 MAPK on the AICAR-induced increase in fatty acid oxidation. CONCLUSION: AICAR stimulated the fatty acid oxidation by activating p38 MAPK. This is a novel pathway by which AMPK activation in skeletal muscle increases the fatty acid oxidation

Increased Plasma Dipeptidyl Peptidase IV Activities in ob/ob Mice.: Sang Dal Rhee, Young Sil Lee, Hye Sung Lee, Won Hoon Jung, Hyae Gyeong Cheon, Jin Hee Ahn, Sung Su Kim, Sang Gi Paik, Sung Don Yang; Korean Diabetes J. 2005;29(1):22-29. Published online January 1, 2005

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Abstract PDF: BACKGROUND
Dipeptidyl peptidase IV (DPP IV/CD26), a multi-functional glycoprotein, cleaves and inactivates major insulinotropic hormones, such as glucagon-like protein (GLP)-1 and glucose dependent insulinotrophic polypeptide (GIP). METHODS: The plasma DPP IV activities in ob/ob mice were measured at 4, 8 and 13 weeks of age and the correlation between the plasma glucose concentration and DPP IV activity analyzed at 7~9 weeks of age. The glucose lowering effects of P32/98, a DPP IV inhibitor, was assessed with the oral glucose tolerance test. RESULTS: The plasma DPP IV activities in ob/ob mice were higher than those in lean mice. The plasma DPP IV activity was correlated with the plasma glucose concentration both in male and female ob/ob mice. The glucose lowering effect of DPP IV inhibitor was more prominent in ob/ob than in lean mice. CONCLUSION: The plasma DPP IV activities in ob/ob mice were higher than in lean control mice, which may contribute to the higher glucose lowering effect of the DPP IV inhibitor in ob/ob mice

Genetic Polymorphism of Glucagon-Like Peptide 1 Receptor in Korean Type 2 Diabetes Mellitus.: Kyung Wook Lee, Meihua Jiang, Shanji Piao, Eun A Kim, Seong Bin Hong, Moon Suk Nam, Yong Seong Kim, Kyong Soo Park, Hyun Chul Lee; Korean Diabetes J. 2005;29(1):30-38. Published online January 1, 2005

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Abstract PDF: BACKGROUND
Glucagon-like peptide-1 (GLP-1) is a hormone secreted by intestinal L-cells, which stimulates insulin secretion from cells. The biological action of GLP-1 is mediated by the glucagon-like peptide-1 receptor (GLP-1R), which is 463 amino acids in size, with 7 transmembrane domains. Because GLP-1 plays an important modulatory role in regulating glucose-stimulated insulin, the GLP-1R could be a candidate gene contributing to impaired -cell function and the development of this genetically heterogeneous disorder. Recently, four GLP-1R SNPs were identified in Caucasian diabetic individuals, and for the SNP at the Leu- 260Phe (A/C) position, statistically significant differences were detected in the distribution of genotypes between type 2 diabetic and nondiabetic subjects. We replicated the genetic association between the SNP at the leu260Phe (A/C) position in the GLP-1R gene and Korean type 2 diabetes mellitus. METHODS: The Leu260Phe polymorphism in the GLP-1R gene was determined using a PCR- RFLP method (the genotypes were determined according to the results of polymerase chain reaction products after digestion and the digestive enzyme was BbsI) in 419 Korean type 2 diabetic patients and 345 nondiabetic subjects. RESULTS: In contrast to the Caucasian report, there was no significant difference in the frequencies of alleles, and genotypes between Korean type 2 diabetic and nondiabetic subjects. When analyzed according to gender, BMI and age of onset, the genotype distribution of type 2 diabetic subjects was not significantly different from nondiabetic subjects. CONCLUSION: The Leu260Phe polymorphism in the GLP-1R gene was not associated with type 2 diabetes mellitus, and we were unable to replicate the genetic association between this polymorphism and Korean type 2 diabetes mellitus

Effects of Aging and Obesity on Insulin Secretion and Sensitivity.: J Y Kim, J H Jee, H J Kim, B W Lee, Y J Chung, J H Chung, Y K Min, M S Lee, M K Lee, K W Kim; Korean Diabetes J. 2005;29(1):39-47. Published online January 1, 2005

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Abstract PDF: BACKGROUND
Type 2 diabetes is occurring in epidemic proportions worldwide and aging has been defined as one of the risk factors for the progression to diabetes. The mechanism responsible for deterioration of glucose tolerance with aging is still unclear. It has been debated whether this deterioration results from an abnormal beta cell secretory function or/and decreased insulin sensitivity, from the aging process per se, or some other factors, such as an increase in BMI and abdominal fat. The changes in the insulin secretion and sensitivity were assessed in relation to aging and obesity, and the association between obesity and factors influencing glucose homeostasis in obese subjects evaluated. METHODS: 530 individuals, aged 24 to 75 years, having undergone a 75 g OGTT were enrolled, and the insulinogenic index and HOMA-IR calculated for each subject. 212 individuals were obese, i.e. a BMI above 25, which was evaluated from the body composition by CT at the umbilicus and thigh levels. RESULTS: There was negative correlation between the insulinogenic index and age, but not between HOMA-IR and age. In relation to increasing age, the body composition changed toward a metabolically obese state, with increasing WHR, visceral fat area, VSR and VWR. Both the insulinogenic index and HOMA-IR were positively correlated with the anthropometric parameters. CONCLUSION: The age-associated deterioration in glucose tolerance may be due to decreases in both insulin secretion and insulin sensitivity from changes in body composition

Waist Circumference as a Risk Factor for Metabolic Syndrome in Korean Adult ; Evaluation from 5 Different Criteria of Metabolic Syndrome.: H J Lee, H S Kwon, Y M Park, H N Chun, Y H Choi, S H Ko, J M Lee, K H Yoon, B Y Cha, W C Lee, K W Lee, H Y Son, S K Kang, M S Ahn, J M Kang, D S Kim; Korean Diabetes J. 2005;29(1):48-56. Published online January 1, 2005

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Abstract PDF: BACKGROUND
Many different criteria for defining metabolic syndrome have been suggested. The prevalence of metabolic syndrome differs according to each set of criteria. This study was performed to estimate the prevalence of metabolic syndrome in middle-aged Korean people using five different criteria. METHODS: This was a population based, cross-sectional study including 5,330 participants (2,197 males and 3,133 females), over the age 40, conducted in a rural area of Korea. The prevalence of metabolic syndrome was assessed according to the NCEP-ATP III criterion, Asian Pacific region criterion for abdominal obesity (modified ATP III), WHO criterion, American Association of Clinical Endocrinologists (AACE) and European Group for the Study of Insulin (EGIR) criterion. We performed anthropometry and laboratory test on the 5,330 subjects, and the prevalence of metabolic syndrome was determined according to the five different definition. RESULTS: The prevalence of metabolic syndrome using the modified ATP III, NCEP- ATP III, WHO, AACE and EGIR criteria were 33.8 (27.0% in men and 38.7% in women), 23.8 (17.5% in men and 28.3% in women), 23.7 (26.5% in men and 21.7% in women.), 30.1 (22.4% in men and 35.4% in women) and 15.2% (12.9% in men and 16.9% in women), respectively. CONCLUSION: The prevalence of metabolic syndrome was quite different in the same population according to the different definitions applied. Further studies, including a prospective study on metabolic syndrome, will be needed to clarify the definition and clinical characteristics of metabolic syndrome in Korea

The Thickness of Carotid Artery Intima-Media Thickness in Hypertriglyceridemic Hyperapo B Type 2 Diabetes.: Ji Hyun Lee, Duck Soo Chung; Korean Diabetes J. 2005;29(1):57-64. Published online January 1, 2005

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Abstract PDF: BACKGROUND
Atherosclerotic diseases such as cardiovascular disease and cerebrovascular disease are major causes of diabetes mellitus-related morbidity and mortality. The frequency of macrovascular disease in type 2 diabetic patients varies geographically, and this suggests that factors other than diabetes play an important role in the pathogenesis of their vascular disease. One such factor may be the dyslipoproteinemias that are common in diabetic patients. There were many studies showing that hypertriglyceridemia with an elevated apolipoprotein B (apo B) level was associated with an increased risk for coronary disease in type 2 diabetes patients. Meanwhile, an increase in the intima-media thickness (IMT) of the carotid artery has been previously reported in patients with type 2 diabetes, and this is related to the atherosclerotic risk factors. The aim of this study was to evaluate the relationship between the carotid artery IMT and lipoprotein and apolipoprotein, and we also wanted to assess the role of hypertriglyceridemic hyperapo B for the cardiovascular risk factors in the type 2 diabetic patients. METHODS: The carotid artery IMT was measured using high resolution B-mode ultrasono graphy in 117 type 2 diabetes. At the same time, we analyzed the patients characteristics including height, weight, body mass index, blood pressure, duration of diabetes and history of hypertension. Laboratory parameters such as fasting blood glucose, HbA1c, total cholesterol, triglyceride, LDL-cholesterol, HDL-cholesterol, apolipoprotein A and B were included in this study. We defined hypertrigl yceridemic hyperapo B as when the triglyceride level was over 1.7 mmol/L and the apolipoprotein B level was over 1.20 g/L. RESULTS: Thirty-three patients (28%) were classified as having hypertriglyceridemic hyperapo B. Age (r = 348, P = 0.001), duration of diabetes (r = 0.438, P = 0.001), hypertension (P = 0.001), and LDL-cholesterol (r = 0.225, P = 0.018) were statistically significant for the carotid artery IMT values in diabetic patients. However, there were no correlations between carotid artery IMT and total cholesterol, triglyceride, HDL- cholesterol, and apolipoprotein A and B. Upon multiple regression analysis, age, duration of diabetes and LDL-cholesterol were statistically significant for the carotid artery IMT values in diabetic patients (R2 = 0.296). Hypertriglyceridemic hyperapo B diabetic patients didn't have higher carotid artery IMT values than the other patients. CONCLUSION: The increment of carotid artery IMT is affected by age, blood pressure, duration of diabetes and LDL-cholesterol. However, our study did not show any association between carotid artery IMT and hypertriglyceridemic hyperapo B

Maximal Oxygen Uptake (VO2max) and Metabolic Syndrome.: Mira Kang, Ji Dong Sung, Byung Chul Yoo, Yoon Ho Choi, Sae Young Jae, Jae Hoon Chung, Yong Ki Min, Myung Shik Lee, Kwang Won Kim, Moon Kyu Lee; Korean Diabetes J. 2005;29(1):65-71. Published online January 1, 2005

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Abstract PDF: BACKGROUND
A number of studies have demonstrated an inverse relationship between cardiorespiratory fitness and metabolic syndrome. However, whether the maximal oxygen uptake (VO2max) is dependent on the number of metabolic components or on particular metabolic component remains to be assessed. METHODS: A total of 1,432 Korean subjects were studied. Each individual was assessed for the presence of metabolic syndrome using the modified NCEP-ATP III criteria. All subjects underwent a graded symptom-limited maximal exercise test to determine their VO2max, using a treadmill according to the Bruce protocol. RESULTS: The age-adjusted prevalence of metabolic syndrome in all subjects was 20.4%. The odds ratios for metabolic syndrome were higher in men, the elderly, the obese and those with a lower VO2max. The difference in the VO2max was dependent only on the presence of metabolic syndrome, not on the number of components. CONCLUSION: There were no significant differences in the VO2max according to the presence of particular metabolic components. These results suggest that the VO2max reflects the metabolic syndrome state, rather than the metabolic components, and might be a factor in determining metabolic syndrome

Effects of the Glycemic Index of Dietary Carbohydrates on Insulin Requirement in Type 1 Diabetics on Continuous Subcutaneous Insulin Infusion.: Hye Jin Lee, Kwon Beom Kim, Kyung Ah Han, Kyung Wan Min, Eung Jin Kim, Ki Nam Kim; Korean Diabetes J. 2005;29(1):72-77. Published online January 1, 2005

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Abstract PDF: BACKGROUND
For ideal glycemic control, the pump user should have a meal planning approach that is as precise and flexible as the pump. Counting carbohydrate is simple and works, but is not a perfect system. Many researches indicate that not all carbohydrates create an equal response when it comes to their effect on blood glucose levels. For a better match between the glucose and insulin profiles, the glycemic index as along with counting carbohydrate might be considered. Therefore, we investigated whether the same amount of carbohydrates with different glycemic indices might require different insulin doses. METHODS: Five type 1 diabetics, using portable external pumps, whose basal rates were correctly set to maintain their blood glucose levels with in the target range under 12 hours fasting conditions, were enrolled. 50 grams of 4 carbohydrate containing foods, with different glycemic indices, were administered for 4 consecutive days to diabetic patients in an overnight fasting state. The test foods were rice, apple, milk and orange juice, for which the glycemic indices were 83, 54, 39 and 97, respectively. The insulin requirement for each food was determined so that the blood glucose level reached the target range four hours after eating. RESULTS: The glycemic indices for each food/rice ratio were significantly correlated with the insulin requirement (r = 0.586, P < 0.01). CONCLUSION: The meal-related insulin dose should be changed according to the glycemic index of the meal. Therefore both amount and source of carbohydrate determine the glucose and insulin responses of type 1 diabetic subjects

Case Report

Sphenoid Sinus Aspergillosis with Ophthalmoplegia that Occurred in Patients with Diabetes Mellitus.: Oh Dae Kwon, Jong Yup Bae; Korean Diabetes J. 2005;29(1):78-82. Published online January 1, 2005

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Abstract PDF: Ophthalmoplegia that is caused by spheniod sinus aspergillosis is a rare disease. We report here on two cases of sphenoid sinus aspergillosis with diplopia that occurred in a diabetic patient and an immunocompetent patients. The diabetic patient showed a more rapid progression, severer symptoms and a delayed and incomplete recovery from the neurological deficits. The other patient had milder symptoms, a slower disease course and a more rapid recovery. We suggest that immediate imaging should be performed to diagnose the cause of diplopia in those patients presenting with atypical unilateral persistent facial pain and diplopia, and especially for those patient with diabetes mellitus

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