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Biomedical subjects

B S Cha

Publications and source records attributed to B S Cha.

14 recordsLinked to original sources
PubMed2006

Tissue-specific regulation of malonyl-CoA decarboxylase activity in OLETF rats.

AIM: The intracellular concentration of malonyl-CoA, a key regulator of fatty acid oxidation, is determined both from its synthesis by acetyl-CoA carboxylase and from its degradation by malonyl-CoA decarboxylase (MCD). The aim of our study was to investigate the activity and mRNA expression of MCD under insulin resistance and after treatment with insulin sensitizers in different tissues. METHODS: We treated 18-week Otusuka Long-Evans Tokushima Fatty (OLETF) rats with pioglitazone (10 mg/kg/day) or metformin (300 mg/kg/day) for 8 weeks and determined the activity and mRNA expression of MCD in diabetic OLETF and non-diabetic Long-Evans Tokushima Otsuka (LETO) rats in myocardial and skeletal muscles, and in liver. RESULTS: The MCD activities of myocardial and skeletal muscles were remarkably reduced in OLETF rats compared with LETO rats (995 +/- 114 vs. 2012 +/- 359, 58 +/- 11 vs. 167 +/- 40 pmol/min/mg protein; p = 0.005 and p = 0.010). Surprisingly, after pioglitazone treatment, not after metformin, the MCD activities of myocardial and skeletal muscles (1906 +/- 320 and 259 +/- 44 pmol/min/mg protein) increased up to the levels in LETO rats. MCD mRNA expression in OLETF rats was also reduced in myocardial and skeletal muscles vs. LETO rats (p = 0.049 and p = 0.008) and was unchanged by pioglitazone or metformin treatment. In the liver, MCD activity and mRNA expression were similar in OLETF and LETO rats. CONCLUSION: Pioglitazone treatment restored MCD activity to non-diabetic level and improved the restrained fatty acid metabolism in myocardial and skeletal muscles caused by insulin-resistant diabetic status.

Animals↗
PubMed2004

Sibutramine improves fat distribution and insulin resistance, and increases serum adiponectin levels in Korean obese nondiabetic premenopausal women.

The aim of this study was to evaluate the effects of sibutramine on body composition and fat distribution, insulin resistance, and serum adiponectin levels in obese women. A total of 28 obese, premenopausal women (mean age, 34.5 +/- 13.7 years; BMI, 31.00 +/- 4.10 kg/m2) was studied before and after 12-week-course of sibutramine (10mg/day). Sibutramine treatment reduced body mass index (P < 0.05) and total body fat (P < 0.05). Abdominal subcutaneous and visceral fat areas (ASFA and AVFA) and mid-thigh low density muscle areas (LDMA) measured by computed-tomography decreased significantly (all, P < 0.05). Insulin resistance (IR) calculated from the homeostasis model assessment (HOMA) method decreased (P < 0.05) and serum adiponectin levels increased significantly (P < 0.05). In our sequential data, the changes of fasting serum insulin levels and the HOMA-IR scores, serum free fatty acids and triglyceride levels, serum adiponectin levels and the mid-thigh LDMA preceded significant changes of body weight, total body fat, and abdominal fat distribution, suggesting sibutramine might improve insulin sensitivity directly by alterations of fatty acid metabolism or secondarily by increasing serum adiponectin levels. Conclusively, sibutramine improved fat distribution and insulin resistance, and increased serum adiponectin levels in Korean obese nondiabetic premenopausal women.

Adiponectin↗
PubMed2004

An implication of hypertriglyceridemia in the progression of diabetic nephropathy in metabolically obese, normal weight patients with type 2 diabetes mellitus in Korea.

This study was undertaken to investigate diverse risk factors affecting the progression of diabetic nephropathy (DN) by observing the changes of 24 h urinary albumin excretion (24 h UAE) in 90 abdominally obese, normal weight, type 2 diabetic patients with normo- or micro-albuminuria. Patients were divided into three groups according to the 24h UAE; normo-, micro-, and macro-albuminuria group. After 4 years of follow-up, patients were divided into either progression or non-progression group according to the changes of 24 h UAE. About 37% of the normo-albuminuria group and 18% of the micro-albumiuria group were classified into the progression group. The initial serum creatinine levels and the initial and follow-up post-prandial plasma glucose levels were significantly higher in the progression group than in the non-progression group. Most remarkably, the initial and follow-up serum triglyceride (TG) levels (190 +/- 132 versus 132 +/- 49 mg/dl and 191 +/- 124 versus 133 +/- 41 mg/dl, P < 0.01 in both) were significantly higher in the progression group than in the non-progression group, suggesting hypertriglyceridemia might be included in the progression factors of DN. The increases in 24-hour UAE were positively associated with the initial and follow-up post-prandial plasma glucose levels (P < 0.05 in both), the initial and follow-up serum creatinine levels (P < 0.05 in both), and the initial serum TG levels (P < 0.05). Whereas, insulin users or patients with retinopathy at follow-up (P < 0.05 in both) showed more rapid progression of albuminuria, ACE inhibitors or acarbose (P < 0.05 in both) use turned out to protect against it.

Albuminuria↗
PubMed2004

Insulin sensitivity in physically fit and unfit children of parents with Type 2 diabetes.

AIMS: First-degree relatives of patients with Type 2 diabetes mellitus (T2DM) are often reported to be insulin resistant. We wanted to identify early metabolic abnormalities in this condition, and determine whether they are altered by regular physical training. METHODS: We measured insulin sensitivity using the euglycaemic glucose clamp technique and insulin response to oral glucose in 10 unfit (did not participate in routine physical exercise) offspring of T2DM parents and 10 unfit control subjects, and compared them with six fit (routinely swam for 3 h/day 5 days/week) offspring of T2DM parents and six fit controls with no family history of T2DM. RESULTS: Unfit offspring had a higher plasma glucose response than the other three groups. The mean area under the glucose curve was also significantly higher in unfit offspring than in the other three groups (12.6 +/- 0.6 vs. 10.4 +/- 0.4, 9.6 +/- 0.5, and 9.5 +/- 0.7 mmol/l per hour for the unfit controls, fit offspring and fit controls, respectively; P < 0.05). The corresponding insulin response of unfit offspring was significantly higher at 60 min in the oral glucose tolerance test (OGTT) that that of fit offspring or fit controls. In addition, the mean area under the insulin curve was significantly greater in unfit offspring than in either fit offspring or fit controls (868 +/- 172 vs. 294 +/- 71, 287 +/- 43 mmol/l per hour, respectively; P < 0.05). Moreover, the glucose disposal rate (GDR), measured using a euglycaemic clamp, was significantly lower in unfit and fit offspring than in unfit and fit controls (5.6 +/- 0.3 vs. 8.6 +/- 0.3 mg/kg per minute; P < 0.01 and 9.3 +/- 0.9 vs. 12.1 +/- 0.8 mg/kg per minute, respectively; P < 0.015), whereas the GDR was similar in unfit controls and fit offspring (8.6 +/- 0.4 vs. 9.3 +/- 0.9 mg/kg per minute; P > 0.05). CONCLUSION: These results support the concept that early metabolic abnormalities, as reflected by a decreased GDR (insulin sensitivity) in the offspring of T2DM patients, may be improved by increased physical fitness.

Administration, Oral↗
PubMed2003

Therapeutic effect of recombinant human erythropoietin on anaemia with erythropoietin deficiency in diabetic patients.

AIMS: The aim of this study was to investigate the therapeutic effect of recombinant human erythropoietin (rHuEpo) on anaemia with erythropoietin deficiency in diabetic patients. METHODS: Twenty diabetic patients with anaemia and Epo deficiency were enrolled. All patients were treated with rHuEpo (Epokine; 4000 U/day s.c., three times a week) for 8 weeks. RESULTS: The responder group (n = 14) had significant increments in haemoglobin compared with the non-responder group (n = 6) (P < 0.05). No significant differences were found between the responder and non-responder groups in terms of duration of diabetes mellitus, serum creatinine level, 24-h urine albumin excretion rates, frequency of diabetic microangiopathy, or HbA1c. There was no difference between the two groups in terms of serum iron and total iron-binding capacity (TIBC). Serum ferritin level was significantly higher in the responder group than in the non-responder group (240.3 +/- 108.4, 25.8 +/- 3.0 micro g/l, P < 0.05), as was transferrin saturation (32.7 +/- 7.9%, 21.2 +/- 5.3%, P < 0.05). CONCLUSIONS: rHuEpo could be useful in the treatment of anaemia with erythropoietin deficiency in diabetic patients, and the degree of iron storage and functional iron deficiency might be the main cause of hyporesponsiveness to rHuEpo.

Anemia↗
PubMed2001

beta-Cell dysfunction rather than insulin resistance is the main contributing factor for the development of postrenal transplantation diabetes mellitus.

BACKGROUND: Our study was undertaken to investigate the pathogenesis and possible risk factors for postrenal transplantation diabetes mellitus (PTDM). METHODS: We recruited 114 patients with normal glucose tolerance (NGT) and performed both 75-g oral glucose tolerance tests (OGTT) and short insulin tolerance tests 1 week before and 9-12 months after transplantation. RESULTS: The subjects were classified into three groups by World Health Organization criteria on the basis of OGTT after transplantation: (a) 36 (31.6%) subjects with normal glucose tolerance; (b) 51 (45.7%) subjects with impaired glucose tolerance (IGT); and (c) 27 (23.7%) subjects with postrenal transplantation diabetes mellitus. Dosages of steroid and cyclosporine were equivalent among the three groups. Before transplantation, the fasting and 2-hr plasma glucose and proinsulin/insulin (PI/I) ratios were significantly higher in the IGT and PTDM groups than in the NGT group, but the insulin sensitivity index (ISI) was not significantly different among the three groups. In addition, the area under the curve-insulin on OGTT was significantly lower in the PTDM group than in the NGT group. After transplantation, however, the ISI was increased in all groups. Furthermore, the ISI and PI/I ratios revealed significantly higher values in the PTDM group than in the NGT group after transplantation. CONCLUSIONS: These results revealed that fasting and 2-hr plasma glucose levels, as well as the proinsulin/insulin ratio before transplantation, are both possible indicators of beta-cell dysfunction and may be predictors for the development of PTDM. Furthermore, beta-cell dysfunction, rather than insulin resistance, was proven to be the main factor for the pathogenesis of PTDM.

Adult↗
PubMed2001

Peroxisome proliferator-activated receptor (PPAR) gamma and retinoid X receptor (RXR) agonists have complementary effects on glucose and lipid metabolism in human skeletal muscle.

AIMS/HYPOTHESIS: To determine the independent and potentially synergistic effects of agonists for PPAR gamma and RXR on glucose and lipid metabolism, as well as gene expression, in human skeletal muscle cell cultures. METHODS: Fully differentiated myotubes from non-diabetic subjects and subjects with Type II (non-insulin-dependent) diabetes mellitus were chronically (2 days) treated with LG100268 (4 mumol/l), an RXR agonist, or troglitazone (4.6 mumol/l), a PPAR gamma agonist or both, to determine the effects on glucose uptake, activity of glycogen synthase and palmitate oxidation. RESULTS: The combination of both agents increased glucose uptake (60 +/- 9% compared to control subjects) but not either agent alone (16 +/- 9 and 26 +/- 6% for LG100268 and troglitazone, p < 0.01, respectively). The agent LG100268 alone had little effect on the activity of glycogen synthase but the effect of troglitazone increased with LG100268 (p < 0.05). With chronic exposure, LG100268 upregulated palmitate oxidation (53 +/- 12% increase, p < 0.005), in a way similar to troglitazone (68 +/- 23%, p < 0.005). Synergism was observed when both agonists were combined (146 +/- 38%, p < 0.005 vs either agent alone). Treatment with either agent led to about a twofold increase in the expression of fatty acid transporter (FAT/CD36). Troglitazone upregulated PPAR gamma protein expression, whereas LG100268 had no effect. Furthermore, neither LG100268 nor troglitazone had any effect on the protein expression of RXR isoforms or PPAR alpha. CONCLUSION/INTERPRETATION: Co-activation of PPAR gamma and RXR results in additive or synergistic effects on glucose and lipid metabolism in skeletal muscle, but unlike troglitazone, LG100268 does not alter expression of its own receptor.

CD36 Antigens↗
PubMed2001

Low-dose growth hormone treatment combined with diet restriction decreases insulin resistance by reducing visceral fat and increasing muscle mass in obese type 2 diabetic patients.

OBJECTIVE: To evaluate the effects of low-dose growth hormone (GH) therapy combined with diet restriction on changes in body composition and the consequent change in insulin resistance in newly-diagnosed obese type 2 diabetic patients. DESIGN: Double-blind and placebo-controlled trial of 25-kcal/kg IBW diet daily with GH (n=9; rhGH, 0.15 IU/kg body weight/week) or placebo (n=9) for 12 weeks. SUBJECTS: Eighteen newly-diagnosed obese type 2 diabetic patients (age 42--56 y, body mass index 28.1+/-2.7 kg/m(2)). MEASUREMENTS: Body composition and fat distribution parameters (by bioelectrical impedance analyzer and CT scans), serum IGF-1; serum glucose, insulin and free fatty acid (FFA) during oral glucose tolerance test (OGTT); HbA(1c); serum lipid profiles; and glucose disposal rate (GDR) by euglycemic hyperinsulinemic clamp at baseline and after treatment. RESULTS: The fraction of body weight lost as fat lost was significantly greater (0.98+/-0.39 vs 0.52+/-0.32 kg/kg, P<0.05) and visceral fat area was decreased more in the GH-treated group compared to the placebo-treated group (27.9 vs 21.6%, P<0.05). Lean body mass and muscle area were reduced in the placebo-treated group, whereas an increase in both was observed in the GH-treated group. GDR the was significantly increased in only the GH-treated group (4.67+/-1.05 vs 6.95+/-0.91 mg/kg/min, P<0.05). The GH-induced increase in GDR was positively correlated with the decrease in the ratio of visceral fat area/muscle area (r=0.588, P=0.001). Serum glucose levels and insulin- and FFA-area under the curve during OGTT and HbA(1c) were significantly decreased after GH treatment. LDL-cholesterol level was decreased in only the GH-treated group. CONCLUSION: Low-dose GH treatment combined with dietary restriction resulted not only in a decrease of visceral fat but also in an increase of muscle mass with a consequent improvement of the insulin resistance observed in obese type 2 diabetic patients.

Adipose Tissue↗
PubMed2000

Identification of glucokinase mutation in subjects with post-renal transplantation diabetes mellitus.

Mutations in the glucokinase (GCK) gene are considered to be a possible cause of maturity-onset diabetes of the young. The purpose of this study was to evaluate the contribution of this gene to the development of post-renal transplantation diabetes mellitus (PTDM). Identification of the GCK mutation was attempted in 58 selected renal allograft recipients with PTDM and 45 normal controls. The exons in the GCK gene were examined using polymerase chain reaction (PCR), followed by an analysis of single-stranded DNA conformational polymorphism (SSCP). The abnormal bands were then confirmed by DNA sequencing analysis. The family members of the patients affected with GCK mutation were also examined. Two of the 58 PTDM patients (3. 4%) were found to have GCK mutations. One had the mutation on exon 5 and the other on intron 7. One control subject had the mutation on intron 9. The mutation on exon 5 was identified as a substitution of CCT (proline) for CTT (leucine) at codon 164, which has never been reported before. The family members of the PTDM patient with a mutation on exon 5 were analyzed by PCR, followed by SSCP, and two of them had the same mutation. The abnormal band seen on SSCP analysis of exon 7 was identified as the C-->T substitution at the 39th nucleotide in intron 7. Two of the family members also displayed the same bands on the SSCP. One of the 45 normal controls had a known polymorphism located at the 8th nucleotide in intron 9. We found a GCK mutation on the exon in subjects with PTDM and we speculate that this mutation may be one of the possible contributing factors of PTDM, although variations of the GCK gene are not common causes of PTDM.

Adult↗
PubMed2000

Chronic alcohol intake differently influences glucose metabolism according to nutritional status.

We investigated the potential different effects of a chronic alcohol intake on glucose metabolism according to nutritional status in growing rats. Eighty weanling 4-week-old male Sprague Dawley rats were fed with low (5%, wt/wt) or control (22%) protein diet for 8 weeks. Each group was subdivided into alcohol (5 g/kg(-1) x day(-1)) or saline gavage rats during the last 4 weeks. At 12 weeks of age, we measured the weights of the body, pancreas, and epididymal fat; glycogen synthase activity of gastrocnemius muscle; and insulin content of the pancreas. We performed an ip glucose tolerance test and a euglycemic hyperinsulinemic clamp test. Weight gain was almost arrested in protein-deficient rats. The relative weight and insulin content of the pancreas and glycogen synthase activity were not different among the four groups, but the relative amount of epididymal fat decreased only in protein-deficient saline rats. Insulin response after glucose challenge and glucose disposal rate during the euglycemic clamp were both markedly decreased in protein-deficient saline rats, but not changed in protein-deficient alcohol rats. Protein-deficiency per se causes deterioration both in insulin secretory function and in sensitivity, but these defects are protected by a chronic alcohol intake. In a protein-sufficient state, alcohol intake gives no additional effects on glucose metabolism. Therefore, according to individual nutritional status, the metabolic effect of alcohol intake appears differently.

Adipose Tissue↗
PubMed1997

Effect of obesity on total and free insulin-like growth factor (IGF)-1, and their relationship to IGF-binding protein (BP)-1, IGFBP-2, IGFBP-3, insulin, and growth hormone.

OBJECTIVES: We investigated the effect of obesity on the serum levels of total and free IGF-1 and their relationship to the circulating levels of insulin and IGF binding proteins (IGFBPs) in age and sex-matched groups. SUBJECTS: The study included 43 obese subjects (ideal body weight; IBW > 120%) and 45 controls (IBW < 100%). All of the subjects were male. MEASUREMENT: Total IGF-1, free IGF-1, IGFBP-1, IGFBP-2, IGFBP-3, and insulin were measured in obese subjects and normal control subjects. RESULTS: No significant differences in the circulating levels of total and IGFBP-3 were observed between the obese and control groups. In contrast to total IGF-1, free IGF-1 in obese subjects was significantly increased compared to normal controls (P < 0.05). Serum total and free IGF-1 were inversely correlated with age (r = -0.42, P = 0.001, and -0.44, P = 0.001). Fasting serum insulin concentrations were elevated in all the obese subjects (P < 0.05) and positively correlated with IBW (r = 0.57, P = 0.001). The levels of serum GH and IGFBP-1 were suppressed in all the obese subjects (P < 0.05). IGFBP-1 was inversely correlated with IBW (r = -0.51, P = 0.001) and serum insulin concentrations (r = -0.48, P = 0.001). The IGFBP-2 concentrations were also suppressed in obese subjects and inversely related to free IGF-1 (r = -0.48, P = 0.001). Using multiple linear regression analysis, total IGF-1 and insulin concentrations were positively correlated (r = 0.58, P = 0.001) and free IGF-1 and IGFBP-1 concentrations were negatively correlated (r = -0.57, P = 0.001). CONCLUSION: We confirmed that total IGF-1 and IGFBP-3 concentrations were not significantly different between the obese and control groups, despite GH hyposecretion in obesity. We also found that free IGF-1 concentrations were higher in obese subjects than in normal controls. It seems likely that overnutrition and chronic hyperinsulinaemia in obesity may alter this regulated growth response by insulin stimulation of IGF-1 production and suppression of hepatic IGFBP-1 and IGFBP-2 production, which may inhibit IGF-1 bioactivity.

Adult↗
PubMed1995

Relationships among 64k autoantibodies, pancreatic beta-cell function, HLA-DR antigens and HLA-DQ genes in patients with insulin-dependent diabetes mellitus in Korea.

OBJECTIVES: Among autoantibodies detected in patients with insulin-dependent diabetes mellitus (IDDM), antibodies to 64,000(Mr) islet protein(64k), now recognized as glutamic acid decarboxylase(GAD), appear to be an even more predictive marker of IDDM than islet cytoplasmic antibody (ICA) or insulin autoantibody (IAA). We examined the relationships among 64k autoantibodies, pancreatic beta-cell function, HLA-DR antigens and HLA-DQ genes in patients with IDDM in Korea. METHODS: To identify the 64k autoantibody, the immunoprecipitation method was performed for 35 patients with IDDM and 10 normal controls. In patients with IDDM, serum C-peptide levels were measured and HLA-DR typings and HLA-DQA1 and DQB1 gene typings were performed. RESULTS: 12 of 35 (34%) patients with IDDM were positive for 64k autoantibody in contrast to none of 10(0%) normal controls. There were no differences in residual pancreatic beta-cell function between 64k autoantibody positive and negative groups. 64k autoantibody was detected more frequently in patients with recent (duration < 6 months, 10/25[40%]) and young -aged(aged < 15 years, 7/18[39%]) onset of IDDM. All of 3(100%) patients with HLA-DR3/DR4 heterotypes were positive in 64k autoantibody, in contrast to 1 of 7(14%) patients without HLA-DR3 nor DR4. The frequencies of HLA-DQA1*0301, HLA-DQB1*0201, DQB1* 0302 and DQB1*0303 gene types were higher in patients with 64k autoantibody (12/12 [100%]) vs. without 64k autoantibody 18/22[81%], 5/11[45%] vs. without 64k autoantibody 5/22[23%], 5/11[45%] vs. without 64k autoantibody 8/22[36%] and 6/11 [55%] vs. without 64k autoantibody 9/22[41%]. CONCLUSIONS: There results suggest that 64k autoantibodies have some relationship with HLA-DR, DQA1 and DQB1 genes, but not with residual pancreatic beta-cell function in Korean patients with IDDM.

Adolescent↗