Diabetes & Metabolism Journal

Volume 31(6); November 2007

Review

The Role of Glomerular Podocytes in Diabetic Nephropathy.: Eun Young Lee, Choon Hee Chung; Korean Diabetes J. 2007;31(6):451-454. Published online November 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.6.451

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Diabetic nephropathy is the most common cause of end-stage renal disease and accounts for significant morbidity and mortality among individuals with diabetes mellitus. Therefore, the clarification of the pathogenesis of diabetic nephropathy is an urgent issue. Podocytes cover the outer layer of the glomerulus and maintain its integrity so that fluid and toxins exit in urine, but cells and important proteins are kept in the blood stream. Diabetes mellitus alters this structure, it becomes scarred and then the ability of the kidney to clear toxins is lost. Recent evidence shows that early in diabetes the podocyte number is reduced, areas of the glomerular basement membrane are denuded, and podocyte number predicts long-term urinary albumin excretion in the patients with diabetes and microalbuminuria. These results suggest that podocytes play a critical role in the early stage of diabetic nephropathy. It is the purpose of this article to review the pathogenetic role of podocytes in diabetic nephropathy.

Citations

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Inhibition of dipeptidyl peptidase-4 (DPP4), antioxidant, antiglycation and anti-inflammatory effect of Ferulic acid against streptozotocin toxicity mediate nephropathy in diabetic rats
Maryam A. AL-Ghamdi, Said S. Moselhy
Environmental Science and Pollution Research.2022; 30(12): 33942. CrossRef
Study of Antiglycation, Hypoglycemic, and Nephroprotective Activities of the Green Dwarf Variety Coconut Water (Cocos nucifera L.) in Alloxan-Induced Diabetic Rats
Isabella F.D. Pinto, Railmara P. Silva, Adriano de B. Chaves Filho, Lucas S. Dantas, Vanderson S. Bispo, Isaac A. Matos, Felipe A.M. Otsuka, Aline C. Santos, Humberto Reis Matos
Journal of Medicinal Food.2015; 18(7): 802. CrossRef
Effects of ferulic acid on diabetic nephropathy in a rat model of type 2 diabetes
Ran Choi, Bo Hwan Kim, Jarinyaporn Naowaboot, Mi Young Lee, Mi Ri Hyun, Eun Ju Cho, Eun Soo Lee, Eun Young Lee, Young Chul Yang, Choon Hee Chung
Experimental and Molecular Medicine.2011; 43(12): 676. CrossRef

Original Articles

Association of Kir6.2 and Peroxisome Proliferator-activated Receptor-gamma (PPARgamma) Polymorphisms with Type 2 Diabetes in Koreans.: Jung Eun Lee, Su Won Kim, Hyun Ae Seo, Jae Han Jeon, Seong Su Moon, Hee Kyung Kim, Yun Jeong Doh, Bo Wan Kim, Jung Guk Kim, Min Yoo, In Kyu Lee; Korean Diabetes J. 2007;31(6):455-464. Published online November 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.6.455

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Abstract PDF: BACKGROUND
The type 2 diabetes is a typical polygenic disease complex, for which several common risk alleles have been identified. Several variants may contribute significantly to the risk of type 2 diabetes conferring insulin resistance of liver, muscle and fat (Pro12Ala) and a relative insulin secretory deficiency (Glu23Lys). In this study, we evaluated the association of Pro12Ala variant of the peroxisome proliferator- activated receptor-gamma and the Glu23Lys variant of the ATP-sensitive potassium channel, Kir6.2 (KCNJ11) with the type 2 diabetes in Korean population. METHOD: This study included 331 subjects consisting of 172 patients with type 2 diabetes and 159 non- diabetic control subjects enrolled from the Kyungpook, Keimyung and Catholic university hospital in Daegu, Korea. We genotyped Kir6.2 (Glu23Lys) and PPARgamma (Pro12Ala) polymorphism and examined their association with the type 2 diabetes. RESULT: In the separate analyses, the Kir6.2 Glu23Lys (P = 0.385) and the PPARgamma Pro12Ala (P = 0.191) polymorphism showed no significant association with type 2 diabetes. In addition, the results of our study showed no evidence of a synergistic interaction between Kir6.2 and PPARgamma gene in each group (P = 0.110, P = 0.276). CONCLUSION: In this study, no association was seen between the genetic polymorphisms of Kir6.2, PPARgamma and type 2 diabetes. However, to clarify whether genetic polymorphisms of these genes contribute to the development of type 2 diabetes, further studies involving larger Korean populations may be needed.

Comparison of Minicircle with Conventional Plasmid for the Non-viral Vascular Endothelial Growth Factor (VEGF) Gene Therapy.: Minjeong Kwon, Soonhee Lee, Heysook Chung, Changshin Yoon, Mikyung Kim, Jeonghyun Park; Korean Diabetes J. 2007;31(6):465-471. Published online November 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.6.465

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Abstract PDF: BACKGROUND
Delayed wound healings in diabetic patients are related with the impairment of the expressions of various growth factors. Treatments using growth factors have been attempted on diabetic foot ulcer. VEGF (vascular endothelial growth factor) accelerates neo-angiogenesis on the early phase of the wound healing and exerts chemo-attractive effect for the other growth factors and cytokines. Non-viral gene transfer strategies are attractive tool for the gene therapy due to the safety and the versatility, but the low efficiency has been the serious problem. METHODS: We performed the VEGF gene therapy using reconstructed minicircle MINI-pbetaVEGF DNA with a polymeric carrier, polyethylenimine (PEI, 25 kDa) in HEK293, CHO, and NIH3T3 cell lines, and compared its efficiency with the conventional VEGF plasmid pbetaVEGF. RESULTS: The levels of expressed VEGF were higher in the groups using BPEI (branched PEI) as a gene carrier than naked plasmid transfer in all cell lines (P < 0.05). The minicircle MINI-pbetaVEGF DNA showed much higher VEGF expression than conventional plasmid pbetaVEGF (P < 0.05). CONCLUSION: Minicircle DNA MINI-pbetaVEGF showed much higher transfection efficiency than conventional plasmid pbetaVEGF. It might be used in actual human clinical trial due to its higher efficiency and possible safety for the treatment of diabetic foot ulcer.

Inflammatory Markers are Associated with Microvascular Complications in Type 2 Diabetes.: Sun Mee Yang, Sung Yong Kim, Ki Young Lee, Yeun Sun Kim, Moon Suk Nam, Ie Byung Park; Korean Diabetes J. 2007;31(6):472-479. Published online November 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.6.472

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Abstract PDF

BACKGROUND
Inflammatory markers are known to be sensitive predictors of atherosclerotic disease such as coronary heart disease. Diabetic patients have higher level of inflammatory markers such as fibrinogen, high sensitivity C-reactive protein (hsCRP) or IL-6. We investigated the association of inflammatory markers with microvascular complications in type 2 diabetes. METHODS: We studied cross-sectionally 244 consecutive patients with type 2 diabetes without macrovascular disease such as cerebral infarct, coronary heart disease and peripheral arterial disease. The urinary albumin/creatinine ratio was determined in a morning, untimed, urine specimen. Ophthalmoscopic examinations were performed to evaluate diabetic retinopathy. Diabetic neuropathy was examined by 10-g monofilament, Neuropathic Disability Score and Michigan Neuropathy Screening Instrument. RESULTS: 47 patients (23.5%) had diabetic retinopathy, 81 (34.6%) had nephropathy and 132 (54.2%) had neuropathy. Fibrinogen and erythrocyte sedimentation rate (ESR) were significantly higher in the patients with nephropathy, retinopathy and neuropathy than in those without (P = 0.009, 0.003 and 0.047; P = 0.011, 0.02 and 0.006 , respectively). There were no differences in the hsCRP and IL-6 level between in patients with microvascular complications and in those without. Inflammatory parameters were correlated with each other. The hsCRP was correlated with IL-6 (r = 0.40, P < 0.001) and fibrinogen (r = 0.45, P < 0.001), but fibrinogen was not significantly correlated with IL-6 (r = 0.13, P = 0.08). CONCLUSION: Although IL-6, hsCRP and fibrinogen may be associated with microvascular complications in type 2 diabetes, we show that fibrinogen is a strong marker of microvascular complications.

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Hesperetin suppresses LPS/high glucose-induced inflammatory responses via TLR/MyD88/NF-κB signaling pathways in THP-1 cells
Aeri Lee, HyunJi Gu, Min-Hee Gwon, Jung-Mi Yun
Nutrition Research and Practice.2021; 15(5): 591. CrossRef

Peroxisome Proliferator-activated Receptor-gamma (PPARgamma) Polymorphism in Korean Women with Polycystic Ovary Syndrome.: Jee Young Oh, Hyejin Lee, Young Sun Hong, Yeon Ah Sung, Hye Won Chung; Korean Diabetes J. 2007;31(6):480-487. Published online November 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.6.480

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Abstract PDF: BACKGROUND
Polycystic ovary syndrome (PCOS) is a common endocrine disease affecting 5~10% of women with reproductive age. Familial aggregation suggests the evidence supporting a genetic basis for PCOS. The mode of inheritance of PCOS is not yet clear, however, probably polygenic and might be related to insulin resistance. Polymorphism of peroxisome proliferator-activated receptor (PPAR)-gamma gene is a susceptible gene for the development of obesity and diabetes. In this study, we examined the frequency and genetic effect of PPAR-gamma polymorphism on insulin resistance or hyperandrogenemia in Korean women with PCOS. METHODS: One-hundred twenty five Korean women with PCOS were evaluated for their metabolic and reproductive hormonal status. PPAR-gamma polymorphism was analyzed. RESULTS: Genetic frequency of PPAR-gamma was not significantly different between women with PCOS (n = 125) and those with regular menstrual cycles (n = 344). PCOS with Pro12Ala polymorphism had significantly higher levels of waist circumference and subcutaneous fat area compared with those with Pro12Pro genotype. They also had tendency of higher levels of fasting glucose concentration, body mass index (BMI) and visceral fat area. After BMI adjustment, this polymorphism was related to lower fasting insulin and higher insulin sensitivity index, and higher sex hormone binding globulin and lower free testosterone levels. CONCLUSION: Pro12Ala polymorphism of PPAR-gamma gene might be associated with obesity. However, after BMI adjustment, it may have favorable effect on insulin resistance and hyperandrogenemia. Because this study has limitations to conclude the genetic causality, further study is needed to support these findings.

The Effect of Alpha-Lipoic Acid on the Protection of Epidermal Nerve Fibers and Microcapillaries in the Streptozotocin-Induced Diabetic Rats.: Ming Han Piao, Heung Yong Jin, Sun Kyung Song, Seun Mi Kang, So Young Kim, Ji Hyun Park, Hong Sun Baek, Tae Sun Park; Korean Diabetes J. 2007;31(6):488-497. Published online November 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.6.488

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Abstract PDF: BACKGROUND
Diabetic neuropathy is associated with risk factors for macrovascular diseases and other microvascular complications. Alpha-lipoic acid (ALA) administration has been reported to improve metabolic abnormalities and ameliorate peripheral polyneuropathy in diabetic patients. In addition, ALA improves endoneurial nutritive neural blood flow and nerve conduction velocity in diabetic rats. But it is not clear whether ALA has a preservation effect on microvasculature in addition to the effect on intraepidermal nerve fibers (IENFs). We investigated the effect of ALA on intraepidermal nerve fiber density (numbers/mm) and cutaneous capillary length in streptozotocin-induced diabetic rats. METHODS: The rats were randomly divided into 3 groups: diabetes without diet control, diabetes with diet control, and diabetes with ALA treatment. Diabetes was induced by a single intraperitoneal injection of streptozotocin (60 mg/kg) and the effect of ALA treatment was assessed by IENF immunostained with protein gene product 9.5 and by quantification of total cutaneous capillary length with mouse anti-rat reca-1 immunostaining. RESULTS: The value of IENF density significantly increased in ALA treatment group compared with other groups (P < 0.05). Quantification of microvascularity was also significantly increased in ALA treatment group compared with other groups (P < 0.05). CONCLUSION: The results of this study suggest that ALA administration in diabetic rats may be beneficial in the prevention of peripheral neuropathy associated with improvement of microvascularity. And the symptomatic amelioration after ALA treatment may be attributed to this morphological improvement.

Relationship between Endothelial-dependent/-independent Vasodilation and Carotid Intimal- media Thickness in Newly-diagnosed Korean Type 2 Diabetic Patients.: Jung Ho Choi, Kyung Wan Min, Hyo Jeong Kim, Bo kyung Koo, Chae Young Lim, Hyun Jin Kim, Gang Seo Pak, Kyung Ah Han, Eung Jin Kim; Korean Diabetes J. 2007;31(6):498-506. Published online November 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.6.498

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Abstract PDF: BACKGROUND
The relative effect of diabetes on the risk of cardiovascular disease in Asian population is much the same as that in Western populations. Although multiple atherosclerotic risk factors have been documented in Asia, precise estimates of vascular reactivity might provide more critical informations for the prevention and the control of diabetes-related cardiovascular mortality and morbidity. The aims of this study were to estimate the vascular reactivity directly and evaluate its relationship with other cardiovascular risk factors and carotid intimal-media thickness (IMT) in newly-diagnosed Korean type 2 diabetic patients. METHODS: We measured flow-mediated vasodilation (FMD) and endothelial-independent vasodilation (EID) of the brachial artery using high-resolution ultrasonography in total of 121 (M; N = 68, F; N = 53) diabetic patients. We assessed conventional cardiovascular risk factors such as age, smoking, obesity, hypertension, hyperlipidemia or family history of cardiovascular disease and analyzed the association among FMD/EID with cardiovascular risk factors, carotid IMT or the total number of risk factors. RESULTS: The mean values of age, smoking, BMI, waist, systolic blood pressure and diastolic blood pressure were 51.2 +/- 12.3 years, 11.0 +/- 15.8 pack years, 25.0 +/- 3.2 kg/m2, 86 +/- 9 cm, 123 +/- 16 mmHg and 79 +/- 12 mmHg. The mean values of HbA1c, fasting blood glucose, total cholesterol, triglyceride, LDL-cholesterol and HDL-cholesterol were 8.4 +/- 2.0%, 166 +/- 51 mg/dL, 187 +/- 37 mg/dL, 166 +/- 143 mg/dL, 114 +/- 30 mg/dL and 46 +/- 12 mg/dL. FMD and EID were estimated by 6.1 +/- 2.8% and 16.6 +/- 5.6% respectively. The mean/maximal carotid IMT were 0.63 +/- 0.12/0.76 +/- 0.16 mm and the number of risk factors besides diabetes mellitus were 2.3 +/- 1.3. After adjusting age, FMD was associated only with smoking, but EID was associated with smoking, systolic/diastolic blood pressure, mean/maximal carotid IMT and number of risk factors by partial correlations. Age, smoking and EID were independent risk variables for carotid IMT, analyzed by multiple regression test. CONCLUSION: These findings suggest that impaired vascular reactivity detected by EID is closely related to carotid IMT, an useful surrogate marker for atherosclerosis, in newly-diagnosed Korean type 2 diabetic patients.

The Plasma Adiponectin Levels in Patients with Newly Diagnosed Type 2 Diabetes.: Ihn Suk Lee, Yun Jeung Kim, Jong Im Kim, Jea Hyung Park, Bon Jeong Ku, Kang Seo Park, Tae Yong Lee, Young Kun Kim; Korean Diabetes J. 2007;31(6):507-516. Published online November 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.6.507

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Abstract PDF: BACKGROUND
Adiponectin is secreted from adipose tissue and plays an important role in the regulation of glycemia and insulin resistance. In this study, the relationship between adiponectin and the adiposity, body composition, insulin sensitivity, lipid profile were respectively examined in newly diagnosed type 2 diabetes. METHODS: Total 1993 were participated in the Korea Rural Genomic Cohort Study (Geumsan County). After a 12-hour overnight fast, all subjects underwent 75-g oral glucose tolerance test. 105 of those were studied as newly diagnosed type 2 diabetes. The body composition was analyzed by means of bioelectric impedance analysis and the insulin sensitivity was estimated by fasting insulin, HOMA-IR and QUICKI method, respectively. RESULTS: Adiponectin positively correlated with high-density lipoprotein cholesterol (r = 0.246, P < 0.05). Adiponectin inversely associated with waist circumference (r = - 0.408, P < 0.01), triglyceride (r = -0.274, P < 0.05), ferritin (r = -0.260, P < 0.05), visceral fat (r = -0.248, P < 0.05), high sensitivity C-reactive protein (r = -0.228, P < 0.05) and body mass index (r = -0.225, P < 0.05). In multiple linear regression, waist circumference and high-density lipoprotein cholesterol were analyzed as independent variables of serum adiponectin. CONCLUSION: Adiponectin concentrations were closely related to waist circumference in newly diagnosed type 2 diabetes.

Case Reports

A Case of Insulinoma Associated with Type 2 Diabetes Mellitus.: Sung Soo Yoo, Wan Sub Shim, Chul Hyun Kim, Ki Cheol Ha, Seung Min Lye, Eun Joo Kim, So Hun Kim, Seong Bin Hong, Moonsuk Nam, Yong Seong Kim; Korean Diabetes J. 2007;31(6):517-519. Published online November 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.6.517

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Abstract PDF: An insulinoma is an endocrine tumor of the pancreas derived from the beta cells with abnormal insulin secretion. An insulinoma is rare, the incidence being estimated at only four per one million person-years. The association of diabetes mellitus and insulinoma is extraordinarily rare, but we should not overlook an insulinoma as a possible cause of hypoglycemia in patients with diabetes mellitus. A 70-year-old diabetic man who had been treated with oral hypoglycemic agents for type 2 diabetes suffered from night sweating for 10 days. Even after he stopped taking his oral hypoglycemic agents, the night sweating continued. The patient was admitted to evaluate the cause of the recurrent hypoglycemic events. After a 72-hour fasting test and selective arterial calcium stimulation test with venous sampling, he was diagnosed with insulinoma accompanied by type 2 diabetes mellitus. In the course of the study, the patient was also incidentally diagnosed with lung cancer.

A Case of Cured Diabetes Mellitus after Occult Malignant Pheochromocytoma Removal.: Ho Chan Cho, Hye Soon Kim, Yoon Jung Kim, Yu Jin Hah, Nam Keong Kim, Mi Kyung Kim, Keun Gyu Park, Yong Hoon Kim, Sun Young Kwon; Korean Diabetes J. 2007;31(6):520-524. Published online November 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.6.520

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Abstract PDF

Pheochromocytoma is characterized by a combination of various clinical manifestations that include the classic triad of severe headache, palpitations and diaphoresis. In addition, hyperglycemia can be caused by overproduction of catecholamines, which are secreted by a catecholamine-secreting neoplasm of adrenal or extra-adrenal chromaffin tissue. We encountered a case of diabetes with an occult malignant adrenal pheochromocytoma, who did not have any classic manifestations. A 37-year-old male was admitted because of polydipsia, polyuria, and weight loss. Fasting blood glucose level was 497 mg/dL, hemoglobin A1c level was 15%, and diabetic retinopathy and peripheral polyneuropathy were also accompanied. Incidentally, right adrenal mass was detected by ultrasonography of abdomen. Urinary excretion of total metanephrine and epinephrine were elevated. Adrenal CT showed a 7.1 cm sized right adrenal cystic mass with enhancing solid portion and hemorrhagic content. The scan with 123I-MIBG revealed the cystic mass with increased rim uptake in the region of right adrenal gland. After removal of the tumor, the increased levels of catecholamine were normalized. Moreover, blood glucose level was normalized without administration of insulin or oral hypoglycemic agents. The pathologic examination showed that the neoplasm was a malignant adrenal pheochromocytoma. We report this case that diabetes was cured after removal of malignant tumor with literature review at first in Korea.

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Pheochromocytoma with Markedly Abnormal Liver Function Tests and Severe Leukocytosis
Chai Ryoung Eun, Jae Hee Ahn, Ji A Seo, Nan Hee Kim
Endocrinology and Metabolism.2014; 29(1): 83. CrossRef

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