• Molecules and Cells
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• v.43 no.1
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• pp.66-75
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• 2020

Saturated fatty acids contribute to β-cell dysfunction in the onset of type 2 diabetes mellitus. Cellular responses to lipotoxicity include oxidative stress, endoplasmic reticulum (ER) stress, and blockage of autophagy. Palmitate induces ER Ca²⁺ depletion followed by notable store-operated Ca²⁺ entry. Subsequent elevation of cytosolic Ca²⁺ can activate undesirable signaling pathways culminating in cell death. Mitochondrial Ca²⁺ uniporter (MCU) is the major route for Ca²⁺ uptake into the matrix and couples metabolism with insulin secretion. However, it has been unclear whether mitochondrial Ca²⁺ uptake plays a protective role or contributes to lipotoxicity. Here, we observed palmitate upregulated MCU protein expression in a mouse clonal β-cell, MIN6, under normal glucose, but not high glucose medium. Palmitate elevated baseline cytosolic Ca²⁺ concentration ([Ca²⁺]_i) and reduced depolarization-triggered Ca²⁺ influx likely due to the inactivation of voltage-gated Ca²⁺ channels (VGCCs). Targeted reduction of MCU expression using RNA interference abolished mitochondrial superoxide production but exacerbated palmitate-induced [Ca²⁺]_i overload. Consequently, MCU knockdown aggravated blockage of autophagic degradation. In contrast, co-treatment with verapamil, a VGCC inhibitor, prevented palmitate-induced basal [Ca²⁺]_i elevation and defective [Ca²⁺]_i transients. Extracellular Ca²⁺ chelation as well as VGCC inhibitors effectively rescued autophagy defects and cytotoxicity. These observations suggest enhanced mitochondrial Ca²⁺ uptake via MCU upregulation is a mechanism by which pancreatic β-cells are able to alleviate cytosolic Ca²⁺ overload and its detrimental consequences.

• Journal of Applied Biological Chemistry
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• v.53 no.1
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• pp.44-50
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• 2010

Tae-Um-Jo-wee-Tang (TUJWT) and Do-Dam-Tang (DDT) have been used as an anti-obesity herbal medicine but their effect and mechanism of action have not been studied. We investigated the effects of TUJWT and DDT on energy and glucose homeostasis using Sprague Dawley female rats with diet-induced obesity. The mechanisms of action of TUJWT and DDT were studied whether they had anti-obesity effects. Rats fed a high-fat diet were divided into 3 groups: rats in each group received 2 g water extracts of modified TUJWT and DDT, or 2 g cellulose per kg body weight (a negative control) on a daily basis. A further group was fed a low-fat diet as a positive control. We found that DDT significantly decreased body weight and body fat (mesenteric fat and retroperitoneal fat) more than the control. This decrease was due to the reduction in energy intake but no changes of energy expenditure. However, DDT increased fat oxidation as a major energy source than the control. In addition, modified TUJWT and DDT improved glucose tolerance without changing serum insulin levels during an oral glucose tolerance test. In conclusion, DDT have a better anti-obesity effect than TUJWT by decreasing energy intake in female rats with diet-induced obesity. It also improves glucose tolerance.

• Journal of Pharmaceutical Investigation
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• v.33 no.3
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• pp.171-178
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• 2003

Drug interactions with food, on occasion, lead to serious nutritional and functional changes in the body as well as alterations of pharmacological effect. It, therefore, should be necessary to take drug interactions with food into consideration for effective and safe therapeutics. Diabetes mellitus is a heterogeneous group of disorders characterzed by abnormal glucose homeostasis, resulting in hyperglycemia, and is associated with increased risk of microvascular, macrovascular, and neuropathic complications. However, the precise mechanism of diabetes mellitus remains unclear. Three basic objectives in the care of diabetic patients are maintaining optimal nutrition, avoiding hypo- or hyperglycemia and preventing complications. Laminaria japonica is a brown macroalgae which can be used as a functional diet due to high content of diatery fiber. The purpose of this study was to investigate the effect of Laminaria japonica diet on the pharmacokinetics of metformin which are frequently used in the treatment of diabetes. Diabetic rats induced by streptozotocin were employed in this study. Blood concentrations of oral hypoglycemic agent, metformin, were measured by HPLC and resultant pharmacokinetic parameters were calculated by RSTRIP. The mechanisms of drug interaction with food were evaluated on the basis of pharmacokinetic parameters such as $k_{a},\;t_{1/2},\;C_{max},\;t_{max}$, and AUC. Administration of metformin in normal and diabetic rats treated with Laminaria japonica diet showed significant decrease in AUC, $C_{max},\;and\;k_a$, and increase in $t_{max}$, compared to those with normal diet. This might result from adsortion of metformin on components of Laminaria japonica, causing delayed absorption. The oral glucose test showed that Laminaria japonica diet could lower blood glucose level probably through either inhibiting the activity of disaccharidases, intestinal digestive enzymes, or delaying the absorption of glucose. More studies should be followed to fully understand pharmacokinetic changes of metformin caused by long-term Laminaria japonica diet.

• Korean Journal of Veterinary Research
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• v.39 no.1
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• pp.77-84
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• 1999

Anesthetic agents are useful in inducing the anesthesia for surgical operations and various biological experiments, but they can disturb the body homeostasis and cause the stress in animals. Much efforts have been directed on reducing such side effects of anesthesia. In this work, we measured the serum ACTH, corticosterone and glucose concentration in rabbits to compare the degree of stress induced by two commonly-used anesthetics, ketamine, xylazine, and the combination of xylazine and ketamine. 1. The anesthesia was induced in about 10 min in the rabbits treated with xyalzine, ketamine and xylazine-ketamine. The duration of complete loss of righting reflex were 12, 13 and 115 min in the groups treated with xylazine, ketamine and xylazine-ketamine, respectively. 2. Serum ACTH concentrations in all treatment groups were higher than those in control group. At 30 min after the administration of the drugs, serum ACTH levels in ketamine-treated group were significantly higher than those in control, xylazine- and xylazine-ketamine-treated groups. However, at 1, 2, 5 and 9 hours after the drug administration, serum ACTH levels in xylazine-treated-group were higher than those in control. 3. Serum corticosterone levels in xylazine- and xylazine-ketamine-treated groups were lower than those in control or ketamine-treated groups at 0.5 and 1 hour after the administration. However, at 5 and 9 hours after the administration, serum corticosterone levels in xylazine- and xylazine-ketamine-treated groups were significantly higher than those in ketamine-treated group or control. 4. Serum glucose levels transiently increased to 3 times of the pre-injection levels at 0.5 and 1 hours after the administration in xylazine or xylazine-ketamine-treated groin, but were not changed in control and ketamine-treated group. These results indicate that xylazine-induced stress lasts longer than ketamine-induced, suggesting that the difference in stress-related hormone levels during anesthesia could be due to the differences in modes of actions of individual drugs used and the depth of anesthesia.

• The Korea Journal of Herbology
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• v.32 no.1
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• pp.15-23
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• 2017

Objectives : It is well known that Sibjotang (Shizaotang), traditional herbal medicine formula, regulates the body fluid blood pressure homeostasis. This study is to investigate whether Sibjotang improves diabetic renal dysfunction in type II diabetes mellitus animal model, db/db mice. Methods : The animals model were divided into three groups at the age of 8 weeks; control group (C57BLKS/J-db/m mice), diabetic group [(C57BLKS/J+Lepr)-db/db mice], and Sibjotang group [(C57BLKS/J+Lepr)-db/db mice + Sibjotang 100 mg/kg/day]. During 8 weeks of treatment, blood glucose and urinary albumin excretion were checked in metabolic chamber at 8, 12, and 16 weeks of age, respectively. Results : Body weight and food intake of diabetic group were significantly higher than control group after 8 weeks administration. However, there were not significant different between the diabetic group and Sibjotang group. Urinary albumin excretion was significantly decreased in the Sibjotang group than the diabetic group. In addition, supplementation with Sibjotang significantly lowered levels of blood glucose, insulin, and homeostatic model assessment-insulin resistance (HOMA-IR), suggesting reduced insulin resistance. The ratio of mesangial matrix/glomerular area was markedly larger in diabetic group than control group, whereas Sibjotang significantly reduced this expansion. Moreover, immunohistological study revealed that Sibjotang attenuated the increase of transforming growth $factor(TGF)-{\beta}$ expression in kidney. Conclusion : Sibjotang ameliorates diabetes-associated renal injury through the improvement of the blood glucose and insulin sensitivity, and inhibiting the $TGF-{\beta}1$ expression. Therefore, Sibjotang may be a new therapeutic formula for the treatment of diabetic-associated renal dysfunction.

• Clinical and Experimental Pediatrics
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• v.49 no.6
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• pp.665-671
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• 2006

Purpose : To study the effects of growth hormone(GH) treatment on glucose metabolism and insulin resistance in children with idiopathic short stature(ISS). Methods : Glucose and insulin concentrations were measured during oral glucose tolerance test (OGTT) before and after GH treatment(0.6-0.7 IU/kg/week) in 20 patients with ISS. Insulin resistance was assessed by homeostasis model assessment(HOMA). Results : During OGTT, the mean blood glucose level did not show any significant changes after GH treatment. However, mean blood insulin levels of fasting and 30 minutes of OGTT showed significant increases after GH treatment, accompanying significant increases of insulin resistance. There was no difference in change of glucose, insulin levels and insulin resistance before and after GH treatment between two groups of body mass indices(BMI) of 25< and >25. There also was no significant difference between two groups of with and without family histories of diabetes mellitus (DM). There was no case of newly developed impaired glucose tolerance, fasting glucose tolerance, nor newly developed DM. Conclusion : GH treatment with doses of 0.6-0.7 IU/kg/week for mean 9.6 months in patients with ISS did not show any significant changes in blood glucose levels during OGTT. However, GH treatments induced considerably higher fasting insulin levels compared to pretreatment, resulting in statistically higher insulin resistance. Higher BMI and family history of DM did not induce any significant changes in glucose, insulin level and insulin resistance after GH treatment than the other groups.

• Development and Reproduction
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• v.20 no.3
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• pp.187-196
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• 2016

The objective of the current study was to determine acute plasma stress responses in two size groups of juvenile Epinephelus akaara (average body weight: $8.4{\pm}2.1$ and $3.3{\pm}0.6g$; 150 and 120 days after hatch, respectively) exposed to abrupt salinity drops (from 34 practical salinity unit, PSU seawater to 18, 10 PSU (experiment 1) or 26, 18, 10 PSU (experiment 2), respectively). Plasma glucose, glutamic oxalate transaminase, glutamic pyruvate transaminase, red blood cell counts, and gill histology were determined during 72 h exposure. Significantly increased plasma glucose, glutamic oxalate transaminase levels, and red blood cell counts were observed in fish exposed to 18 or 10 PSU. Histological changes, such as hyperplasia and lifting of epithelium in the gill secondary lamellae, were also observed in fish exposed to 18 or 10 PSU at 72 h post-drop. E. akaara exposed to sudden salinity drops to 18 or 10 PSU still seems to undergo the primary adjustment phase before fish reaches a new homeostasis, whereas fish exposed to 26 PSU seems to mount osmotic changes. Therefore, the no observed adverse effect levels for 72 h acute salinity challenge was 26 PSU in our study, and salinity drop to 18 PSU and below can possibly cause acute adverse effect, in which fish could be vulnerable to additional stresses such as a temperature changes or handling stress.

• The Korean Journal of Nuclear Medicine
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• v.18 no.1
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• pp.39-44
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• 1984

It is well known that glucagon, like insulin, is very important in the moment-to-moment control of the homeostasis of glucose, and of amino acids. Glucagon has been shown to have potent glycogenolytic, gluconeogenic and lipolytic activities. Attention to its role in the pathogenesis of diabetes mellitus and hypoglycemia has been also advanced recently. To evaluate the diurnal variation of plasma glucagon concentration, we measured serum glucose, insulin, and plasma glucagon every 30 minutes or every hour in 7 normal Korean adults. Results were as follows: 1) Although plasma glucagon concentration showed wide individual variations, it had a tendency to decrease after meals. After lunch and dinner, plasma glucagon concentration had gradually declined and reached its nadir at postprandial 2-2.5 hours. The minimal level of plasma glucagon was at 4 A.M. 2) Serum insulin:plasma glucagon ratios were increased promptly after meals. Especially after lunch, its peak was prominent $(3.65{\pm}1.95)$. The minimal level of serum insulin:plasma glucagon ratio appeared at 6 A.M.

• Nutrition Research and Practice
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• v.8 no.2
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• pp.172-176
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• 2014

BACKGROUND/OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is becoming an important public health problem as metabolic syndrome and type 2 diabetes have become epidemic. In this study we investigated the protective effect of Cordyceps militaris (C. militaris) against NAFLD in an obese mouse model. MATERIALS/METHODS: Four-week-old male ob/ob mice were fed an AIN-93G diet or a diet containing 1% C. militaris water extract for 10 weeks after 1 week of adaptation. Serum glucose, insulin, free fatty acid (FFA), alanine transaminase (ALT), and proinflammatory cytokines were measured. Hepatic levels of lipids, glutathione (GSH), and lipid peroxide were determined. RESULTS: Consumption of C. militaris significantly decreased serum glucose, as well as homeostasis model assessment for insulin resistance (HOMA-IR), in ob/ob mice. In addition to lowering serum FFA levels, C. militaris also significantly decreased hepatic total lipids and triglyceride contents. Serum ALT activities and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-6 (IL-6) levels were reduced by C. militaris. Consumption of C. militaris increased hepatic GSH and reduced lipid peroxide levels. CONCLUSIONS: These results indicate that C. militaris can exert protective effects against development of NAFLD, partly by reducing inflammatory cytokines and improving hepatic antioxidant status in ob/ob mice.

• Molecules and Cells
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• v.40 no.6
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• pp.393-400
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• 2017

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by lack of insulin and high glucose levels. T2DM can cause bone loss and fracture, thus leading to diabetic osteoporosis. Promoting osteogenic differentiation of osteoblasts may effectively treat diabetic osteoporosis. We previously reported that Sirtuin 1 (Sirt1), a $NAD^+$-dependent deacetylase, promotes osteogenic differentiation through downregulation of peroxisome proliferator-activated receptor (PPAR) ${\gamma}$. We also found that miR-132 regulates osteogenic differentiation by downregulating Sirt1 in a $PPAR{\beta}/{\delta}$-dependent manner. The ligand-activated transcription factor, $PPAR{\alpha}$, is another isotype of the peroxisome proliferator-activated receptor family that helps maintain bone homeostasis and promot bone formation. Whether the regulatory role of $PPAR{\alpha}$ in osteogenic differentiation is mediated via Sirt1 remains unclear. In the present study, we aimed to determine this role and the underlying mechanism by using high glucose (HG) and free fatty acids (FFA) to mimic T2DM in MC3T3-E1 cells. The results showed that HG-FFA significantly inhibited expression of $PPAR{\alpha}$, Sirt1 and osteogenic differentiation, but these effects were markedly reversed by $PPAR{\alpha}$ overexpression. Moreover, siSirt1 attenuated the positive effects of $PPAR{\alpha}$ on osteogenic differentiation, suggesting that $PPAR{\alpha}$ promotes osteogenic differentiation in a Sirt1-dependent manner. Luciferase activity assay confirmed interactions between $PPAR{\alpha}$ and Sirt1. These findings indicate that $PPAR{\alpha}$ promotes osteogenic differentiation via the Sirt1-dependent signaling pathway.