Alpha-lipoic acid attenuates adipocyte differentiation and lipid accumulation in 3T3-L1 cells via AMPK-dependent autophagy

Hahm, Jong Ryeal,Noh, Hae Sook,Ha, Ji Hye,Roh, Gu Seob,Kim, Deok Ryong Elsevier 2014 Life sciences Vol.100 No.2

RKIP phosphorylation–dependent ERK1 activation stimulates adipogenic lipid accumulation in 3T3-L1 preadipocytes overexpressing LC3

Hahm, Jong Ryeal,Ahmed, Mahmoud,Kim, Deok Ryong Elsevier 2016 Biochemical and biophysical research communication Vol.478 No.1

<P><B>Abstract</B></P> <P>3T3-L1 preadipocytes undergo adipogenesis in response to treatment with dexamethaxone, 1-methyl-3-isobutylxanthine, and insulin (DMI) through activation of several adipogenic transcription factors. Many autophagy-related proteins are also highly activated in the earlier stages of adipogenesis, and the LC3 conjugation system is required for formation of lipid droplets. Here, we investigated the effect of overexpression of green fluorescent protein (GFP)-LC3 fusion protein on adipogenesis. Overexpression of GFP-LC3 in 3T3-L1 preadipocytes using poly-<SMALL>L</SMALL>-lysine-assisted adenoviral GFP-LC3 transduction was sufficient to produce intracellular lipid droplets. Indeed, GFP-LC3 overexpression stimulated expression of some adipogenic transcription factors (e.g., C/EBPα or β, PPARγ, SREBP2). In particular, SREBP2 was highly activated in preadipocytes transfected with adenoviral GFP-LC3. Also, phosphorylation of Raf kinase inhibitory protein (RKIP) at serine 153, consequently stimulating extracellular-signal regulated kinase (ERK)1 activity, was significantly increased during adipogenesis induced by either poly-<SMALL>L</SMALL>-lysine-assisted adenoviral GFP-LC3 transduction or culture in the presence of dexamethasone, 1-methyl-3-isobutylxanthine, and insulin. Furthermore, RKIP knockdown promoted ERK1 and PPARγ activation, and significantly increased the intracellular accumulation of triacylglycerides in DMI-induced adipogenesis. In conclusion, GFP-LC3 overexpression in 3T3-L1 preadipocytes stimulates adipocyte differentiation via direct modulation of RKIP-dependent ERK1 activity.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Overexpression of GFP-LC3 in 3T3-L1 cells produces intracellular lipid droplets. </LI> <LI> SREBP2 is highly activated in preadipocytes transfected with adenoviral GFP-LC3. </LI> <LI> RKIP phosphorylation at serine 153 is significantly increased during adipogenesis. </LI> <LI> RKIP knockdown promotes ERK1 and PPARγ activation during adipogenesis. </LI> <LI> RKIP-dependent ERK1 activation increases triacylglycerides in adipocytes. </LI> </UL> </P>

Comparative analysis of fat and muscle proteins in fenofibrate-fed type II diabetic OLETF rats: the fenofibrate-dependent expression of PEBP or C11orf59 protein

( Jong Ryeal Hahm ),( Jin Sook Ahn ),( Hae Sook Noh ),( Seon Mi Baek ),( Ji Hye Ha ),( Tae Sik Jung ),( Yong Jun An ),( Duk Kyu Kim ),( Deok Ryong Kim ) 생화학분자생물학회 (구 한국생화학분자생물학회) 2010 BMB Reports Vol.43 No.5

Fenofibrate, an agonist of PPARα, plays an important role in activating many proteins catalyzing lipid metabolism, and it also has a considerable effect on improvement of insulin sensitivity in the diabetic condition. To investigate fenofibrate- dependent expression of peripheral tissue proteins in diabetes, we analyzed whole muscle or fat proteins of fenofibrate-fed OLETF rats, an animal model of type II diabetes, using 2-dimensional gel electrophoresis. We found that many proteins were specifically expressed in a fenofibrate-dependent manner in these diabetic rats. In particular, a functionally unknown C11orf59 protein was differentially expressed in the muscle tissues (about 5-fold increase) in fenofibrate-fed OLETF rats as compared to control rats. Additionally, the signal proteins phosphatidylethanolamine binding protein and IkB interacting protein were differentially regulated in the fenofibrate-treated adipose tissues. We suggest here that these proteins might be involved in controlling lipid or carbohydrate metabolism in diabetes via PPARα activation. [BMB reports 2010; 43(5): 337-343]

원저 및 증례 : 조기에 발견된 횡문근융해를 동반한 전격성 제1형 당뇨병 1예

백종하 ( Jong Ha Baek ),이경주 ( Kyeong Ju Lee ),함종렬 ( Jong Ryeal Hahm ),정정화 ( Jung Hwa Jung ),김수경 ( Soo Kyoung Kim ),정순일 ( Soon Il Chung ),정태식 ( Tae Sik Jung ) 대한당뇨병학회 2010 임상당뇨병 Vol.11 No.1

Fulminant type 1 diabetes is characterized by an abrupt onset, severe diabetic ketoacidosis at diagnosis and a relatively low HbA1c. Rhabdomyolysis is not uncommonly combined with diabetic ketoacidosis or hyperglycemic hyperosmolar coma. Rhabdomyolysis increases the development of acute renal failure and mortality of the patients with hyperglycemic diabetic emergency. A 34-year-old man presented with 2-days duration of oliguria, vomiting and lethargy. Formerly, he developed polyuria and flu-like symptoms such as generalized myalgia and headache for 7 days. Initial investigation showed metabolic acidosis (arterial pH 7.093, bicarbonate 5.1 mmol/L), severe hyperglycemia (glucose 1,576 mg/dL), a relatively low HbA1c (7.1%) and acute renal failure (blood urea nitrogen 77 mg/dL and creatinine 4.4 mg/dL). Both serum and 24-hour urine C-peptide levels were checked at very low range and islet autoantibody tests were all negative. Serum creatinine kinase was elevated to 2,397 U/L and urine myoglobin test was positive. The patient recovered from acute renal failure and rhabdomyolysis after fluid and insulin therapy. He discharged on admission 17th days and controlled diabetes by self injection of basal and bolus insulin. (Korean Clinical Diabetes J 11:79-85, 2010)

폐 선양낭성암에 동반된 중추성 요붕증으로 발현한 뇌하수체 종양 1예

이강완,함종렬,정정화,강미연,이기동,김현진,정순일 대한내분비학회 2003 Endocrinology and metabolism Vol.18 No.3

저자들은 다음, 다뇨의 증상을 호소한 52세 여자환자에서 폐에 원발성으로 발생한 선양낭성암의 전이로 추정되는 뇌하수체 종양에 의한 중추성 요봉증을 경험하였기에 문헌 고찰과 함께 증례 보고하는 바이다. The metastatic tumor occurs in about 6% to 20% of all cases with central diabetes insipidus. Many kinds of cancers such as breast, lung, colon, prostate, leukemia, and lymphoma can metastasize to the pituitary and its stalk. Primary adenoid cystic carcinoma arising in the bronchus is an uncommon disease. It is histologically and ultrastructurally identical to salivary gland adenoid cystic tumor and is regarded as a slowly growing, low graded-malignancy. This is a case report of a 52-year-old woman with diabetes insipidus caused by a pituitary tumor that might have been associated with adenoid cystic carcinoma arising in the bronchus. The patient was diagnosed by water deprivation test, chest CT scan, bronchoscopic biopsy, and brain MRI scan. The water deprivation test showed the patient had central diabetes insipidus, while chest CT scan revealed a lung mass lesion with distal right intermediate bronchial obstruction. The primary malignancy was confirmed by bronchoscopic biopsy. Finally, we confirmed that the patient had a 7mm-sized in the posterior pituitary gland and a thickened stalk by brain MRI scan (J Kor Soc Endocrinol 18:311~317, 2003).

Assessment of glycemic control in patients with type 2 diabetes mellitus treated with metformin–sulfonylurea combination: Results of a multicenter, cross-sectional, observational study in Korea

Kim, Sin Gon,Hahm, Jong Ryeal,Kim, Duk Kyu,Cho, Sung Rae,Choi, Dong Seop John Wiley & Sons Ltd 2015 Journal of diabetes investigation Vol.6 No.3

<P><B>Aims/Introduction</B></P><P>To assess the current status of glycemic control in patients with type 2 diabetes treated with a combination of metformin and sulfonylurea for >3 months, as measured by glycosylated hemoglobin (HbA1c).</P><P><B>Materials and Methods</B></P><P>Data on patient demographics, diabetic complications, HbA1c, fasting plasma glucose (FPG) and type of treatment were collected in this multicenter, cross-sectional, non-interventional study.</P><P><B>Results</B></P><P>From April 2008 to February 2009, 5,628 patients were recruited from 299 centers in Korea. Patients characteristics (mean ± SD) were as follows: age 58.4 ± 10.8 years, duration of diabetes 6.1 ± 4.7 years, body mass index 24.7 ± 2.9 kg/m<SUP>2</SUP>, HbA1c 7.77 ± 1.22%, FBG 147.4 ± 46.5 mmol/L and FPG 164.0 ± 54.3 mmol/L. The most common diabetic complication was neuropathy (22.5%), followed by retinopathy (18.3%) and microalbuminuria (16.1%). Just 1,524 (27.1%) patients achieved HbA1c ≤7%. A higher number of patients (32.6%) treated by endocrinologists achieved HbA1c ≤7% than those treated by internists (24.4%) and primary care physicians (23.2%). In multivariate analyses, diabetic retinopathy (odds ratio 0.455, 95% confidence interval 0.341–0.606), nephropathy (odds ratio 0.639, 95% confidence interval 0.43–0.949), diabetes for ≥5 years (odds ratio 0.493, 95% confidence interval 0.4–0.606) and older age added by 1 year (odds ratio 1.019, 95% confidence interval 1.01–1.029) was significantly associated with achieving target HbA1c. In addition, treatment by endocrinologists rather than internists significantly increased chances of achieving target HbA1c (odds ratio 1.417, 95% confidence interval 1.146–1.751).</P><P><B>Conclusions</B></P><P>The majority of patients with type 2 diabetes in Korea had inadequate glycemic control, despite receiving a combination of metformin and sulfonylurea.</P>

Prognostic value of total triiodothyronine and free thyroxine levels for the heart failure in patients with acute myocardial infarction

( Min Gyu Kang ),( Jong Ryeal Hahm ),( Kye-hwan Kim ),( Hyun-woong Park ),( Jin-sin Koh ),( Seok-jae Hwang ),( Jin-yong Hwang ),( Jong Hwa Ahn ),( Yongwhi Park ),( Young-hoon Jeong ),( Jeong Rang Park 대한내과학회 2018 The Korean Journal of Internal Medicine Vol.33 No.3

Background/Aims: Although a low triiodothyronine (T3) state is closely associated with heart failure (HF), it is uncertain whether total T3 levels on admission is correlated with the clinical outcomes of acute myocardial infarction (AMI). The aim of this study is to investigate the prognostic value of total T3 levels for major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with AMI undergone percutaneous coronary intervention (PCI). Methods: A total of 765 PCI-treated AMI patients (65.4 ± 12.6 years old, 215 women) between January 2012 and July 2014 were included and 1-year MACCEs were analyzed. We assessed the correlation of total T3 and free thyroxine (fT4) with prevalence of 1-year MACCEs and the predictive values of total T3, fT4, and the ratio of total T3 to fT4 (T3/fT4), especially for HF requiring re-hospitalization. Results: Thirty patients (3.9%) were re-hospitalized within 12 months to control HF symptoms. Total T3 levels were lower in the HF group than in the non-HF group (84.32 ± 21.04 ng/dL vs. 101.20 ± 20.30 ng/dL, p < 0.001). Receiver operating characteristic curve analysis showed the cut-offs of total T3 levels (≤ 85 ng/dL) and T3/fT4 (≤ 60) for HF (area under curve [AUC] = 0.734, p < 0.001; AUC = 0.774, p < 0.001, respectively). In multivariate analysis, lower T3/fT4 was an independent predictor for 1-year HF in PCI-treated AMI patients (odds ratio, 1.035; 95% confidential interval, 1.007 to 1.064; p = 0.015). Conclusions: Lower levels of total T3 were well correlated with 1-year HF in PCI-treated AMI patients. The T3/fT4 levels can be an additional marker to predict HF.

A 27-Year-Old Woman Diagnosed as Polycystic Ovary Syndrome Associated with Graves' Disease

Jung, Jung Hwa,Hahm, Jong Ryeal,Jung, Tae Sik,Kim, Hee Jin,Kim, Ho Soo,Kim, Sungsu,Kim, Soo Kyoung,Lee, Sang Min,Kim, Deok Ryong,Choi, Won Jun,Seo, Yeong Mi,Chung, Soon Il The Japanese Society of Internal Medicine 2011 Internal medicine Vol.50 No.19

<P>Polycystic ovary syndrome (PCOS) and Graves' disease are the common causes of menstrual irregularity leading to infertility in women of child-bearing age. A 21-year-old female patient visited us with complaints of oligomenorrhea and hand tremor. She was diagnosed as having PCOS and hyperthyroid Graves' disease, simultaneously. She had low body weight (BMI: 16.4 kg/m<SUP>2</SUP>), mild hirsutism, and thyrotoxicosis. The patient was treated with anti-thyroid drug and beta-blocker for about two years, and then recovered to normal thyroid function. Although some studies have suggested a connection between PCOS and autoimmune thyroiditis, no study indicated that PCOS is associated with Graves' disease until now. Here, we describe the first case report of a lean woman with normal insulin sensitivity presenting PCOS and Graves' disease simultaneously.</P>

A Case of Hyperglycemic Hyperosmolar State Associated with Graves' Hyperthyroidism: A Case Report

Moon, Sung Won,Hahm, Jong Ryeal,Lee, Gyeong-Won,Kang, Mi Yeon,Jung, Jung Hwa,Jung, Tae Sik,Lee, Kang Wan,Jung, Kyoung Ah,Ahn, Yong Jun,Kim, Sunjoo,Kim, Me Ae,Kim, Deok Ryong,Chung, Soon Il,Park, Myoun The Korean Academy of Medical Sciences 2006 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.21 No.4

<P>Hyperglycemic hyperosmolar state (HHS) is an acute complication mostly occurring in elderly type 2 diabetes mellitus (DM). Thyrotoxicosis causes dramatic increase of glycogen degradation and/or gluconeogenesis and enhances breakdown of triglycerides. Thus, in general, it augments glucose intolerance in diabetic patients. A 23-yr-old female patient with Graves' disease and type 2 DM, complying with methimazole and insulin injection, had symptoms of nausea, polyuria and generalized weakness. Her serum glucose and osmolarity were 32.7 mM/L, and 321 mosm/kg, respectively. Thyroid function tests revealed that she had more aggravated hyperthyroid status; 0.01 mU/L TSH and 2.78 pM/L free T3 (reference range, 0.17-4.05, 0.31-0.62, respectively) than when she was discharged two weeks before (0.12 mU/L TSH and 1.41 pM/L free T3). Being diagnosed as HHS and refractory Graves' hyperthyroidism, she was treated successfully with intravenous fluids, insulin and high doses of methimazole (90 mg daily). Here, we described the case of a woman with Graves' disease and type 2 DM developing to HHS.</P>

Case Reports : A Case of Cushing`s Syndrome Presenting as Endometrial Hyperplasia

Sang Min Lee,Jong Ryeal Hahm,Tae Sik Jung,Jung Hwa Jung,Mi Yeon Kang,Sun Joo Kim,Soon Il Chung 대한내과학회 2008 The Korean Journal of Internal Medicine Vol.23 No.1

We describe here the case of a 39-year-old woman with a cortisol-producing adrenal adenoma and she presented with endometrial hyperplasia and hypertension without the specific characteristics of Cushing`s syndrome. The patient had consulted a gynecologist for menometrorrhagia 2 years prior to her referral and she was diagnosed with endometrial hyperplasia and hypertension. Her blood pressure and the endometrial lesion were refractory despite taking multiple antihypertensives and repetitive dilation and curettage and progestin treatment. On admission, the clinical examination revealed mild central obesity (a body mass index of 22.9 kg/m2, a waist circumference of 85 cm and a hip circumference of 94cm), but there was no hirsutism and myopathy. She showed impaired glucose tolerance on an oral glucose tolerance test. The biochemical hypercortisolemia together with the prolactin and androgen levels were evaluated to explore the cause of her anovulation. Adrenal Cushing`s syndrome was confirmed on the basis of the elevated urinary free cortisol (454 μg/24h, normal range: 20-70) with a suppressed ACTH level (2.0 pg/mL, normal range: 6.0-76.0) and the loss of circadian cortisol secretion. A CT scan revealed a 3.1 cm, hyperechoic, well-marginated mass in the left adrenal gland. Ten months post-adrenalectomy, the patient had unintentionally lost 9 kg of body weight, had regained a regular menstrual cycle and had normal thickness of her endometrium.