• Journal of Yeungnam Medical Science
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• v.14 no.1
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• pp.53-66
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• 1997

Insulin resistance is a prominent feature of diabetic state and has heterogeneous nature. However, the pathogenetic sequence of events leading to the emergence of the defect in insulin action remains controversial. It is well-known that prolonged hyperglycemia and hyperinsulinemia are one of the causes of development of insulin resistance, but both hyperglycemia and hyperinsulinemia stimulate glucose uptake in peripheral tissue. Therefore, it is hypothesized that insulin resistance may be generated by a kind of protective mechanism preventing cellular hypertrophy. In this study, to evaluate whether the acutely increased glucose uptake inhibits further glucose transport stimulated by insulin, insulin sensitivity was measured after preloaded glucose infusion for 2 hours at various conditions in rats. And also, to evaluate the mechanism of decreased insulin sensitivity, insulin receptor binding affinity and glucose transporter 4 (GLUT4) protein of plasma membrane of gastrocnemius muscle were assayed after hyperinsulinemic euglycemic clamp studies. Experimental animals were divided into five groups according to conditions of preloaded glucose infusion: group I, basal insulin ($14{\pm}1.9{\mu}U/ml$) and basal glucose ($75{\pm}0.7mg/dl$), by normal saline infusion; group II, normal insulin ($33{\pm}3.8{\mu}U/ml$) and hyperglycemia ($207{\pm}6.3mg/dl$), by somatostatin and glucose infusion; group III, hyperinsulinemia ($134{\pm}34.8{\mu}U/ml$) and hyperglycemia ($204{\pm}4.6mg/dl$), by glucose infusion; group IV, supramaximal insulin ($5006{\pm}396.1{\mu}U/ml$) and euglycemia ($l00{\pm}2.2mg/dl$), by insulin and glucose infusion; group V, supramaximal insulin ($4813{\pm}687.9{\mu}U/ml$) and hyperglycemia ($233{\pm}3.1mg/dl$), by insulin and glucose infusion. Insulin sensitivity was assessed with hyperinsulinemic euglycemic clamp technique. The amounts of preloaded glucose infusion(gm/kg) were $1.88{\pm}0.151$ in group II, $2.69{\pm}0.239$ in group III, $3.54{\pm}0.198$ in group IV, and $4.32{\pm}0.621$ in group V. Disappearance rates of glucose (Rd, mg/kg/min) at steady state of hyperinsulinemic euglycemic clamp studies were $16.9{\pm}3.88$ in group I, $13.5{\pm}1.05$ in group II, $11.2{\pm}1.17$ in group III, $13.2{\pm}2.05$ in group IV, and $10.4{\pm}1.01$ in group V. A negative correlation was observed between amount of preloaded glucose and Rd (r=-0.701, p<0.001) when all studies were combined. Insulin receptor binding affinity and content of GLUT4 were not significantly different in all experimental groups. These results suggest that increased glucose uptake may inhibit further glucose transport and lead to decreased insulin sensitivity.

• Journal of Korean Academy of Nursing
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• v.34 no.6
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• pp.1108-1116
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• 2004

Purpose: This research was conducted to provide basic information about the effects of aerobic exercise on physiological change in middle-aged obese women according to differences of ${\beta}$3-adrenergic receptor polymorphisms. Method: Twenty-nine middle aged obese women with over 30%BMI were divided into three groups according to ${\beta}$3-adrenergic receptor gene polymorphism[Variable Group(VG):9, Normal Group(NG):10, Control Group(CG):10]. The VG and NG groups performed walking at 50% exercise intensity for 30 minutes a day, 4 days a week, for 12 weeks. The data was analyzed using the SPSS program. Result: The level of leptin, insulin and % body fat in the VG and NG groups was significantly lower than those of the CG after 12 weeks. In addition, the level of HDL-C in the VG and NG was significantly higher than that of the CG after 12 weeks. However, TC, TG and body weight between groups didn't appear significant at the end of 12 weeks. Conclusions: Aerobic exercise didn't cause differences in persons with differing ${\beta}$3-adrenergic receptor gene polymorphisms, but aerobic exercise affected the physiological change in middle-aged obese women. The findings suggest that aerobic exercise is a desirable nursing intervention for obesity control in middle-aged obese women.

• Korean Journal of Pharmacognosy
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• v.45 no.1
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• pp.28-34
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• 2014

Rhei Rhizoma (RR) and Moutan cortex (MC) have been reported to have anti-inflammatory effects. However, little is known about the effects of RR and MC on endothelial inflammation and insulin resistance (IR). This study aims to investigate whether the water extracts of RR and MC could exert protection against palmitic acid (PA)-induced inflammation and IR in human umbilical vein endothelial cells (HUVECs). HUVECs were pretreated for 6 h with RR or MC, and then exposed to PA for 24 h. The levels of interleukin-6 (IL-6) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) were determined by enzyme-linked immunosorbant assay kits. Western blot analysis was performed for activation of nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and insulin receptor substrate-1 (IRS-1). In HUVECs stimulated with PA, both RR and MC significantly inhibited the production of TNF-${\alpha}$ and IL-6 and the activation of NF-${\kappa}B$. At the same concentrations, the inhibitory effects of RR were more potent than those of MC. PA reduced insulin-induced phosphorylation of IRS-1, which was reversed by RR and MC. The results suggest that RR and MC are effective in inhibiting PA-associated endothelial inflammation and ameliorating IR by beneficial regulation of NF-${\kappa}B$ and IRS-1 activation.

• The Korean Journal of Zoology
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• v.38 no.3
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• pp.426-432
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• 1995

Expression of $\beta$-lactoglobulin gene in mammary tissue is strongly induced by lactogenic hormones such as prolactin, glucocorticoid, and insulin. In order to elucidate the regulatory mechanism underlying such hormonal induction, the response of the caprine $\beta$-lactoglobulin gene promoter to lactogenic hormones was analyzed in cultured HC11 mammary cells. Expression with serial deletions of the 5' -regulatory sequence of the $\beta$-lactoglobulin promoter revealed that two regions are responsible for a substantial change in hormonal indudbility. The region upstream of-1692, which exhibited strong repression of the downstream promoter, mediated the induction by insulin. This insulin-response was independent of the other two lactogenic hormones, prolactin and glucocorticoid. The other region from -740 to -470, which showed strong activation of the $\beta$-lactoglobulin promoter in confluent HC11 mammary cells, mediated mainly the response to a glucocorticoid analogue, dexametasone. The induction by the latter region, however, was suppressed by the usptream repression without insulin treatment. These results suggest that the induction of $\beta$-lactoglobulin promoter activity by lactogenic hormones in mammary cells may be achieved by the combined action of derepression by in sulin and activation by glucocorticoid and prolactin. Dexametasone response by the latter region seems to be mediated by the glucocorticoid receptor site around -7OObp.

• Molecules and Cells
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• v.38 no.12
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• pp.1044-1053
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• 2015

This study first investigated the effects of corn gluten hydrolysate (CGH) (1.5 g/day) administration for 7 days on appetite-responsive genes in lean Sprague-Dawley (SD) rats. In a second set of experiments, the metabolic changes occurring at multiple time points over 8 weeks in response to CGH (35.33% wt/wt) were observed in high-fat (HF, 60% of energy as fat) diet-fed SD rats. In lean rats, the hypothalamus neuropeptide-Y and proopiomelanocortin mRNA levels of the CGH group were significantly changed in response to CGH administration. In the second part of the study, CGH treatment was found to reduce body weight and perirenal and epididymal fat weight. CGH also prevented an increase in food intake at 2 weeks and lowered plasma leptin and insulin levels in comparison with the HF group. This reduction in the plasma and hepatic lipid levels was followed by improved insulin resistance, and the beneficial metabolic effects of CGH were also partly related to increases in plasma adiponectin levels. The Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR), an index of insulin resistance, was markedly improved in the HF-CGH group compared with the HF group at 6 weeks. According to the microarray results, adipose tissue mRNA expression related to G-protein coupled receptor protein signaling pathway and sensory perception was significantly improved after 8 weeks of CGH administration. In conclusion, the present findings suggest that dietary CGH may be effective for improving hyperglycemia, dyslipidemia and insulin resistance in diet-induced obese rats as well as appetite control in lean rats.

• Development and Reproduction
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• v.20 no.3
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• pp.179-185
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• 2016

The insulin-like growth factor (IGF) pathway is a key signal transduction pathway involved in cell proliferation, migration, and apoptosis. In dairy cows, IGF family proteins and binding receptors, including their intracellular binding partners, regulate mammary gland development. IGFs and IGF receptor interactions in mammary glands influence the early stages of mammogenesis, i.e., mammary ductal genesis until puberty. The IGF pathway includes three major components, IGFs (such as IGF-I, IGF-II, and insulin), their specific receptors, and their high-affinity binding partners (IGF binding proteins [IGFBPs]; i.e., IGFBP1-6), including specific proteases for each IGFBP. Additionally, IGFs and IGFBP interactions are critical for the bioactivities of various intracellular mechanisms, including cell proliferation, migration, and apoptosis. Notably, the interactions between IGFs and IGFBPs in the IGF pathway have been difficult to characterize during specific stages of bovine mammary gland development. In this review, we aim to describe the role of the interaction between IGFs and IGFBPs in overall mammary gland development in dairy cows.

• Biomedical Science Letters
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• v.10 no.3
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• pp.203-210
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• 2004

It has been reported that glomerulosclerosis mediated by the dysfunction of mesangial cells and insulin-like growth factors (IGFs) are associated with the development of diabetic nephropathy. However, it is not yet known the effect of high glucose on IGF-I, -II secretion, IGF-I receptor, and IGFBPs expression in the mesangial cells. Thus, this study was conducted to examine the effect of high glucose on IGF system and its involvement of protein kinase C (PKC) and oxidative stress in mesangial cells. In this study, high glucose (25 mM) increased IGF-I and IGF-II secretion and mRNA expression (P<0.05), which was blocked by PKC inhibitor (staurosporine, 10/sup -8/ M) and antioxidant (N-acetyl cystein, 10/sup -5/ M). High glucose decreased IGFBP-1 and -2 expression but increased IGFBP-5 expression. These alteration of IGFBPs by high glucose was also prevented by staurosporine and NAC, suggesting the role of PKC and oxidative stress. Indeed, high glucose increased PKC activity. Furthermore, high glucose-induced increase of lipid peroxide (LPO) formation was blocked by PKC inhibitors. In conclusion, high glucose alters IGF system via PKC-oxidative pathways in mesangial cells.

• Development and Reproduction
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• v.21 no.1
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• pp.93-100
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• 2017

Obesity is characterized by a state of chronic low-grade inflammation and insulin resistance, which are aggravated by the interaction between hypertrophic adipocytes and macrophages. In this study, we investigated the effects of tangeretin on inflammatory changes and glucose uptake in a coculture of hypertrophic adipocytes and macrophages. Tangeretin decreased nitric oxide production and the expression of interleukin (IL)-6, $IL-1{\beta}$, tumor necrosis $factor-{\alpha}$, inducible nitric oxide synthase, and cyclooxygenase-2 in a coculture of 3T3-L1 adipocytes and RAW 264.7 cells. Tangeretin also increased glucose uptake in the coculture system, but did not affect the phosphorylation of insulin receptor substrate (IRS) and Akt. These results suggest that tangeretin improves insulin resistance by attenuating obesity-induced inflammation in adipose tissue.

• Interdisciplinary Bio Central
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• v.3 no.2
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• pp.6.1-6.3
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• 2011

Diabetes Mellitus (DM), often simply referred to as diabetes, has developed into a major health concern affecting more than 200 million people worldwide with approximately 4 million deaths per year attributed to the presence of the disease. Diabetes mellitus is categorized as Type 1 and Type 2, where Type 1 diabetes represents a lack of insulin production, and Type 2 diabetes is characterized by a relative lack of insulin receptor (i.e., decreased sensitivity to the effect of insulin) and cased by a complex interplay between genetic factors and environmental factors. Up to date, various studies on the pathology and mechanism in terms of genetic experiments have been conducted and approximately hundreds of genes were reported as diabetes mellitus associated genes. At this point, to support studies on the cause and mechanism of diabetes mellitus, an efficient database system to provide genetic variants related to diabetes mellitus is needed. DMBase is an integrated web-based genetic information resource for diabetes mellitus designed to service genomic variants, genes, and secondary information derived for diabetes mellitus genetics researchers. The current version of DMBase documents 754 genes with 3056 genetic variants and 66 pathways. It provides many effective search interfaces for retrieving diabetes mellitus and genetic information. A web interface for the DMBase is freely available at http://sysbio.kribb.re.kr/dmBase.

• Food Science of Animal Resources
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• v.43 no.1
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• pp.170-183
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• 2023

This study evaluated the effects of milk fermented with Pediococcus acidilactici strain BE and Pediococcus pentosaceus strain M103 on diabetes in rats (Rattus norvegicus). The bacteria were separately used as starter cultures for milk fermentation, and the products were then fed to diabetic rats for 15 days. Blood glucose levels, immunohistochemical and histological indicators, lipid profiles, and total lactic acid bacterium counts were evaluated before and after treatment. The administration of milk fermented with P. acidilactici strain BE reduced blood glucose levels from 410.27±51.60 to 304.07±9.88 mg/dL (p<0.05), similar to the effects of metformin (from 382.30±13.39 mg/dL to 253.33±40.66 mg/dL, p<0.05). Increased insulin production was observed in diabetic rats fed milk fermented with P. acidilactici strain BE concomitant with an increased number and percentage area of immunoreactive beta-cells. The structure of insulin-producing beta-cells was improved in diabetic rats fed milk fermented with P. acidilactici strain BE or metformin (insulin receptor substrate scores of 5.33±0.94 and 3.5±0.5, respectively). This suggests that the administration of milk fermented with P. acidilactici BE potentially reduces blood glucose levels and improves pancreatic beta-cell function in diabetic rats.