Sung Hee Ihm

The relationship between serum resistin, leptin, adiponectin, ghrelin levels and bone mineral density in middle-aged men

Objective Body weight is a significant predictor of bone mass. Hormonal factors such as sex hormones, insulin, leptin and adiponectin are thought to play a role in the mechanisms controlling the association of body weight and fat mass with bone mass. However, contradictory results have been reported for the association between serum adipocytokines and bone mineral density (BMD). We therefore examined whether the serum adipocytokine and ghrelin levels, markers of fat metabolism, are associated with BMD in male adults.

Circulating osteoprotegerin and receptor activator of NF‐κB ligand system are associated with bone metabolism in middle‐aged males

Objectiveu2002 Osteoporosis is a growing health problem in males as well as in females. Sex hormones and insulin‐like growth factor‐I (IGF‐I) have been shown to be the major determinants in male bone metabolism. Osteoprotegerin (OPG) is a recently identified cytokine that acts as a decoy receptor for the receptor activator of NF‐κB ligand (RANKL). OPG and RANKL have been shown to be important regulators of osteoclastogenesis. However, the relationship between the OPG‐RANKL system and male bone status in human populations are unclear. Thus, the aim of this study was to investigate the relationship between the OPG‐RANKL system and bone mineral metabolism in males.

Insulin dose titration system in diabetes patients using a short messaging service automatically produced by a knowledge matrix.

BACKGROUNDnWe designed a system for diabetes patients treated with glargine, a long-acting insulin, to make an automatic adjustment of insulin dose based on glucose level data and to provide the patients with the needed insulin dose by using a short message service (SMS). We also compared diabetes patients who used our system with patients who received the conventional titration scheme.nnnMETHODSnIncluded were 100 type 2 diabetes patients whose blood glucose was suboptimally controlled on their previous antidiabetes treatment. Each participant was assigned to either the intervention or control group, each with 50 patients, using adaptive randomization. We applied our system to the intervention group for 12 weeks, whereas the control group received a conventional titration scheme, seeking a target fasting blood glucose of <120 mg/dL.nnnRESULTSnThe fasting and postprandial glucose levels of the intervention group declined earlier than those of the control group. Lastly, a greater (P = 0.023) reduction in hemoglobin A(1C) from baseline to the end point was observed in the intervention group (from 9.8 +/- 1.3% to 7.4 +/- 0.7%) than in the control group (from 9.8 +/- 1.2% to 7.8 +/- 0.8%). The incidence of symptomatic, asymptomatic, and nocturnal hypoglycemia was similar in both groups. There was a small increase in body weight from baseline to the end point with both the intervention (2.4 +/- 3.0 kg) and control (2.2 +/- 2.8 kg) groups.nnnCONCLUSIONSnThis study demonstrated that SMS based on our specialized Internet-supported system is an effective and safe approach to long-acting insulin dose adjustments in patients with type 2 diabetes.

Delivery of hypoxia-inducible VEGF gene to rat islets using polyethylenimine

Islet transplantation is a promising strategy for treatment of diabetes. However, islets are exposed to hypoxia in the process of isolation and transplantation and prone to apoptosis. Vascular endothelial growth factor (VEGF) gene transfer is one of the promising strategies to address this problem. However, VEGF expression in the cells under normoxia is undesirable since it may induce pathological angiogenesis. Therefore, VEGF expression should be regulated to avoid this problem. In this study, hypoxia-inducible VEGF gene was transferred to islets using a non-viral carrier. Rat islets were transfected with high molecular weight PEI (25 kDa, PEI25K), low molecular weight PEI (2 kDa, PEI2K), and polyamidoamine dendrimer (PAMAM). PEI25K had higher transfection efficiency to rat islets than PAMAM or PEI2K. The hypoxia-inducible gene expression vector, pRTP801-Luc or pRTP801-VEGF was transferred to rat islets using PEI25K. Transfection assay with pRTP801-Luc showed that luciferase expression was induced in rat islets under hypoxia. In addition, transfer of pRTP801-VEGF showed that VEGF gene expression was higher under hypoxia than normoxia in rat islets. In conclusion, delivery of pRTP801-VEGF using PEI25K induces VEGF level specifically under hypoxia and may be useful for the development of anti-apoptotic strategies for islet transplantation.

Enhanced protection of Ins-1 β cells from apoptosis under hypoxia by delivery of DNA encoding secretion signal peptide-linked exendin-4

In this study, we developed an expression system of exendin-4, a glucagon-like peptide (GLP-1) analog, using a secretion signal peptide (SP) to facilitate exendin-4 secretion. For delivery of the exendin-4 expression system, high-molecular-weight polyethylenimine (25 kDa, PEI25k), low-molecular-weight polyethylenimine (2 kDa, PEI2k), and polyamidoamine (PAMAM) dendrimers were evaluated as gene carriers to Ins-1 β cells. As a result, PEI25k showed the highest transfection efficiency. For the construction of the exendin-4 expression vector, DNA coding the SP sequence was inserted upstream of the exendin-4 cDNA, resulting in the construction of pβ-SP-Ex-4. Transfection assay showed that the secretion level of exendin-4 increased in the pβ-SP-Ex-4 transfected cells, compared with the pβ-Ex-4 transfected cells. To identify the β-cell protection effect of pβ-SP-Ex-4 delivery, the Ins-1 β cells were transfected with pβ-SP-Ex-4 or pβ-Ex-4 and incubated under normoxia or hypoxia. An MTT assay showed that the pβ-SP-Ex-4 transfected cells had higher β-cell viability than the pβ-Ex-4 transfected cells under hypoxia. In addition, the pβ-SP-Ex-4 transfected cells exhibited lower caspase-3 activity than the pβ-Ex-4 transfected cells. Therefore, PEI25k/pβ-SP-Ex-4 complex may be useful to protect isolated β cells from apoptosis during transplantation.

Gestational hyperlipidemia and acute pancreatitis with underlying partial lipoprotein lipase deficiency and apolipoprotein E3/E2 genotype

We report the case of a patient who experienced extreme recurrent gestational hyperlipidemia. She was diagnosed with partial lipoprotein lipase (LPL) deficiency but without an associated LPL gene mutation in the presence of the apolipoprotein E3/2 genotype. This is the first reported case of extreme gestational hyperlipidemia with a partial LPL deficiency in the absence of an LPL gene mutation and the apolipoprotein E 3/2 genotype. She was managed with strict dietary control and medicated with omega-3 acid ethyl esters. A patient with extreme hyperlipidemia that is limited to the gestational period should be considered partially LPL-deficient. Extreme instances of hyperlipidemia increase the risk of acute pancreatitis, and the effect of parturition on declining plasma lipid levels can be immediate and dramatic. Therefore, decisions regarding the timing and route of delivery with extreme gestational hyperlipidemia are critical and should be made carefully.