Endocrinology and Metabolism

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Influence of Vitamin D Deficiency on Progression of Experimental Otitis Media in Rats: Hee-Bok Kim, So Hyun Lim, Chang Gun Cho, Han Seok Choi; Endocrinol Metab. 2018;33(2):296-304. Published online June 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.2.296

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Background

Vitamin D plays an important role in the immune response against infection. The purpose of the present study was to investigate the influence of vitamin D deficiency on the progression of otitis media (OM) using an experimental rat model.

Methods

Four-week-old male Sprague-Dawley rats (n=72) were divided into two groups based on their diet: a control diet group (n=36) and a vitamin D-deficient diet group (n=36). After 8 weeks of diet, experimental OM was induced by inoculation of non-typeable Haemophilus influenzae in the middle ear cavity. The rats were evaluated with otomicroscopy to determine the inflammation in the middle ear mucosa on days 1, 2, 4, 7, and 14 post-inoculation. Bullae from sacrificed rats were collected and analyzed histologically.

Results

The middle ear mucosa from rats with vitamin D deficiency showed a significantly higher thickness than that of controls during the course of OM. The maximum mucosal thickness was 56.0±9.1 µm in the vitamin D deficiency group, and 43.9±9.8 µm in the control group, although there was no significant difference in the tympanic membrane score between the two groups evaluated with otomicroscopy. An immunohistochemical study showed increased expression of interleukin 6 (IL-6) and tumor necrosis factor α in rats manifesting vitamin D deficiency and decreased expression of IL-10 compared with controls.

Conclusion

Our results showed that vitamin D deficiency may exacerbate the pathophysiological changes of OM via altered cytokine production. Therefore, maintaining vitamin D status in the optimal range may be beneficial for proper management of OM.

Citations

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The role of vitamin D in subjective tinnitus—A case-control study
Magdalena Nowaczewska, Stanisław Osiński, Maria Marzec, Michał Wiciński, Katarzyna Bilicka, Wojciech Kaźmierczak, Rafael da Costa Monsanto
PLOS ONE.2021; 16(8): e0255482. CrossRef
Vitamin D and Otitis Media
Rebecca E. Walker, Jim Bartley, Carlos A. Camargo, Edwin A. Mitchell
Current Allergy and Asthma Reports.2019;[Epub] CrossRef

The Effect of Leptin Level Fluctuations by a Repeated Fasting/Refeeding on the Leptin Sensitivity in OLETF Rats.: Sung Chul Park, Yong Hoon Park, So Young Park, Jong Yeon Kim, Yoon Ki Park, Tae Hyung Lee, Kyu Chang Won, Yong Woon Kim; J Korean Endocr Soc. 2008;23(5):310-318. Published online October 1, 2008; DOI: https://doi.org/10.3803/jkes.2008.23.5.310

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BACKGROUND
Leptin resistance is a common feature in obese subjects and animals, and this is commonly accompanied with hyperleptinemia. We speculated that one of the causes of leptin resistance is a persistently elevated leptin concentration and then we hypothesized that fluctuations of serum leptin would increase leptin sensitivity in the leptin-resistant state. METHODS: We used a repeated fasting and refeeding (RFR) protocol to produce fluctuation in leptin levels in 7 month-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats and Long-Evans Tokushima Otsuka (LETO) rats, We then measured the leptin sensitivity following an intracerebroventricular (i.c.v.) infusion of leptin. RESULTS: The OLETF rats exhibited severe visceral fat deposition, hyperleptinemia and leptin resistance. However, in the OLETF-RFR rats, the anorexic effect following i.c.v. leptin infusion was restored. Moreover, the visceral fat mass and serum leptin levels decreased, while the serum adiponectin levels were elevated in the OLETF-RFR rats compared to the OLETF-Control rats. The leptin receptor content in the hypothalamus increased in the OLETF-RFR rats compared to the OLETF-Control rats, and the leptin receptor content in the OLETF-RFR rats decreased compared to that in the the LETO-Control rats. CONCLUSION: These results suggest that the intermittent suppression of the serum leptin level reversed the leptin resistance in OLEFT rats, and this may have occurred due to an increased number of leptin receptors in the hypothalamus.

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Reduced Striatal Dopamine Transporter Availability and Heightened Response to Natural and Pharmacological Stimulation in CCK-1R-Deficient Obese Rats
Sevag Hamamah, Andras Hajnal, Mihai Covasa
International Journal of Molecular Sciences.2023; 24(11): 9773. CrossRef
Improvement of Leptin Resistance
Yong Woon Kim
Yeungnam University Journal of Medicine.2013; 30(1): 4. CrossRef
The Effect of Food Restriction on Appetite Regulating Hormones and Adiponectin Activity
Ki Hoon Kim, Hyun Kook Kim
Korean Journal of Nutrition.2012; 45(1): 5. CrossRef
The Effect of Leptin Level Fluctuations by a Repeated Fasting/Refeeding on the Leptin Sensitivity in OLETF Rats
Min Seon Kim
Journal of Korean Endocrine Society.2008; 23(5): 298. CrossRef

Effects of S-allylcysteine on Oxidative Stress in Streptozotocin-Induced Diabetic Rats.: Chul Ho Shin, Jahei Ihm; J Korean Endocr Soc. 2008;23(2):129-136. Published online April 1, 2008; DOI: https://doi.org/10.3803/jkes.2008.23.2.129

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BACKGROUND
An increase in oxidative stress is postulated to contribute to the development of diabetic complications and the use of antioxidant therapy could be protective against these processes. This study was performed to investigate the role of the antioxidant S-allylcysteine (SAC), a water-soluble component of aged garlic, for reducing levels of oxidative stress that occurs in diabetic rats. METHODS: SAC (100 mg/head/day) was administered orally to streptozotocin-induced diabetic rats for eight weeks. The effects of SAC on the levels of markers of oxidative stress (malondialdehyde and glutathione) and mRNA expression of antioxidant enzymes were measured in the liver and kidney. RESULTS: SAC-fed rats showed lower cholesterol and triacylglyceride levels than untreated diabetic rats. Malondialdehyde levels were increased in the liver and kidney of diabetic rats and SAC administration lowered the levels in both organs. Glutathione levels were lower in the liver and kidney of diabetic rats, and SAC administration restored the glutathione to a level similar in non-diabetic rats. In the liver and kidney of untreated diabetic rats, mRNA expression of catalase, superoxide dismutase and glutathione reductase were down regulated, and administration of SAC increased expression of these enzymes. CONCLUSION: Our results have shown that administration of SAC to diabetic rats can lower blood lipid levels and alleviate oxidative stress in the diabetic tissues, suggesting that SAC might have beneficial effects in a prevention trial for diabetic complications.

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Effect of Garlic and Aged Black Garlic on Hyperglycemia and Dyslipidemia in Animal Model of Type 2 Diabetes Mellitus
Yeong-Ju Seo, Oh-Cheon Gweon, Ji-Eun Im, Young-Min Lee, Min-Jung Kang, Jung-In Kim
Preventive Nutrition and Food Science.2009; 14(1): 1. CrossRef
Antioxidant effect of garlic and aged black garlic in animal model of type 2 diabetes mellitus
Young-Min Lee, Oh-Cheon Gweon, Yeong-Ju Seo, Jieun Im, Min-Jung Kang, Myo-Jeong Kim, Jung-In Kim
Nutrition Research and Practice.2009; 3(2): 156. CrossRef
Effects of Adenophora triphylla Ethylacetate Extract on mRNA Levels of Antioxidant Enzymes in Human HepG2 Cells
Hyun-Jin Choi, Soo-Hyun Kim, Hyun-Taek Oh, Mi-Ja Chung, Cheng-Bi Cui, Seung-Shi Ham
Journal of the Korean Society of Food Science and Nutrition.2008; 37(10): 1238. CrossRef

Naloxone Increases the Anorexic Effect of MTII in OLETF Rats.: Jang Ho Bae, Yong Hoon Park, Sung Ho Kim, So Young Park, Jong Yeon Kim, Jo Young Son, Jung Yoon Huh, Kyu Chang Won, Yong Woon Kim; J Korean Endocr Soc. 2008;23(1):18-26. Published online February 1, 2008; DOI: https://doi.org/10.3803/jkes.2008.23.1.18

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BACKGROUND
Leptin, an adipocyte-derived hormone, inhibits obesity in lean subjects, but is not widely used because of leptin resistance. Thus, circumventing the arcuate nucleus of the hypothalamus, the site responsible for leptin resistance, has been evaluated for treatment of obesity. However, chronic treatment of melanotan II (MTII), a synthetic agonist of the melanocortin 3/4 receptor, induces tachyphylaxis. Here, we evaluated whether naloxone, a non-specific agouti-related peptide (AgRP) antagonist, increases the anorexic effect of MTII in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. METHODS: We measured food intake following intracerebroventricular (i.c.v.) infusion of MTII and/or naloxone in OLETF rats. Sprague-Dawley rats were used as a normal control group. RESULTS: The anorexic effect of i.c.v. MTII infusion decreased with time in OLETF rats, indicating the development of tachyphylaxis. In normal control rats, naloxone alone decreased AgRP expression in the hypothalamus but failed to induce anorexia. Moreover, there was no additional anorexic effect with co-treatment of naloxone and MTII. In OLETF rats, naloxone alone did not show an anorexic effect despite increased POMC expression in the hypothalamus. However, naloxone sensitized the anorexic effect of MTII when treated together. CONCLUSION: These results suggest that naloxone augmented the anorexic effect of MTII when treated together in OLETF rats, but had no effect alone. These results suggest that a combination therapy of naloxone and a melanocortin receptor activator would be an effective modality for treatment of obesity.

Citations

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Naloxone Increases the Anorexic Effect of Melanocortin II
Seungjoon Park
Journal of Korean Endocrine Society.2008; 23(1): 15. CrossRef

Effects of alpha-Lipoic Acid on Bone Metabolism in Rats with Low Bone Mass.: Jung Min Koh, Hee Sook Lee, Duk Jae Kim, Ghi Su Kim; J Korean Endocr Soc. 2005;20(5):476-487. Published online October 1, 2005; DOI: https://doi.org/10.3803/jkes.2005.20.5.476

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Growing evidence has shown a biochemical link between increased oxidative stress and reduced bone density. In our previous study, alpha-lipoic acid (alpha-LA), a thiol antioxidant, suppressed both osteoclastogenesis and bone resorption, and also prevented TNF-alpha-induced apoptosis of osteoblast lineages. The effects of alpha-LA were investigated on bone metabolism in rats with a low bone mass. METHODS: An ovariectomy (OVX) or Talc injection (inflammation-mediated osteopenia, IMO) was performed in 12 week old female Sprague-Dawley rats. Diets containing either 0.3%, 0.5% or 1.0% alpha-LA were administered to the OVX rats for 16 weeks, and to the IMO rats for 21 days. The bone mineral densities (BMD) of the anterior-posterior lumbar spine and total femur were measured using dual-energy X-ray absorptiometry (Hologic QDR 4500-A), with small animal software. The plasma bone specific alkaline phosphatase activity (BSAP) and urinary free deoxypyridinoline concentration (DPD) were determined using enzyme immunoassay methods. RESULTS: The body weights were significantly decreased in the OVX rats on the diets containing 0.3 and 0.5% alpha-LA than in the OVX control. No significant differences in the BMD at either site were noted between rats administered the diets with or without alpha-LA. However, the administration of various doses of alpha-LA noticeably decreased the level of urinary DPD in both the OVX and IMO rats. High doses of alpha-LA (0.5% and/or 1.0%) also decreased the levels of plasma BSAP in both models. CONCLUSION: Although no increase in BMD was demonstrated by the administration of alpha-LA, these results suggest that alpha-LA suppresses the rates of bone turnover in rats with a low bone mass

Regulation of FSH Gene Expression and Release in Cultured Rat Anterior Pituitary Cells.: Min Seok Cheon, Deok Bae Park, Yong Bin Park, Kyung Yoon Kam, Kyung Za Ryu; J Korean Endocr Soc. 2000;15(2):179-189. Published online January 1, 2001

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Abstract PDF: BACKGROUND
FSH is a heterodimeric glycoprotein and is composed of alpha and beta subunits. alpha subunit is common to FSH and LH, while an unique beta subunit determines the biological specificity of each hormone. The synthesis of beta subunit is the primary rate-limiting step in the synthesis of each hormone. Although FSH plays a pivotal role in folliculogenesis and ovulation, very little studies have been performed on the regulation of FSH beta gene expression. Therefore, the present study attempted to examine the effect of GnRH or activin on the expression of FSH beta mRNA as well as FSH release and signaling pathway involved in their actions. METHODS: The primary cultures of rat anterior pituitary were used for this study. To determine FSH beta mRNA levels, northern blotting method was used. The concentration of FSH in the culture medium was evaluated by using a specific radioimmunoassay for rat FSH. RESULTS: PMA, an activator of PKC, increased FSH beta mRNA levels and FSH release, whereas forskolin, an activator of adenylate cyclase, showed no effect. The application of GnRH augmented FSH release, but not FSH beta mRNA levels. However, the administration of activin increased FSH beta mRNA levels as well as FSH release. Staurosporine, an inhibitor of PKC, suppressed activin-induced increment of FSH beta mRNA levels and FSH release. CONCLUSION: The present study demonstrated that activin rather than GnRH is a major regulator for FSH beta mRNA expression, and suggest that PKC-dependent pathway is also involved in the action of activin on the expression of FSH beta mRNA and FSH release.

Effect of ICV Corticosterone on hypothalamic NPY mRNA Expression in food-restricted, Adrenalectomized Rats.: Yeo Joo Kim, Mi Rim Kim, Moon Seok Nam, Yong Sung Kim; J Korean Endocr Soc. 1998;13(2):150-155. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Adrenalectomy does impair the expression of hypothalamic NPY gene in the rat and replacement of glucocorticoid by intracerebroventricular(ICV) route resulted in a normalization of refeeding hyperphagia and weight gain in adrenalectomized(ADX), food-deprived rats. The purpose of this study was to assess the direct effect of CNS glucocorticoid on hypothalamic NPY gene expression which occurs following food deprivation in ADX rats. METHODS: Adult male Wistar rats were fitted with ICV cannulae and restricted the food intake for 14 days. Adrenalectomy and sham operation were done on the 10th day and single ICV corticosterone acetate(100ug/2uL) was given in one ADX group(ADX+CORT, n=9) and vehicle (2uL) was given in another ADX group(ADX+VEH, n=9) and sham rats(SHAM+VEH, n=7). After experiment, we measured NPY mRNA on arcuate nucleus by in situ hybridization. RESULTS: The rate of weight loss of ADX rats closely parallded that of sham-operated rats. Plasma glucose and insulin levels were not significantly different in three groups. Hybridization density on the ARC in ADX+VEH rats(0.42+/-0.02uCi/g: p<0.05) was significantly reduced compared to that in sham controls(0.68+/-0. 11uCi/g). ICV corticosterone injection increased the hybridization density in ADX+CORT rats(0.53+/-0.04uCi/g) compared to vehicle alone, although this did not reach that of controls. NPY gene expression was 40% in ADX+VEH rats and 62% in ADX+CORT rats compared to control rats. CONCLUSIONS: These results are consistent with the hypothesis that CNS glucocorticoid deficiency appears to be responsible for the impairment of refeeding hyperphagia in ADX rats and the effect of CNS glucocorticoid deficiency is a manifestation of impaired activation of hypothalamic NPY gene expression in the ARC.

Antioxidative Effect of Melatonin in Streptozotocin-Induced Diabetic Rats.: Hyung Joon Yoo, Do Ho Moon, Hong Bae Chung, Myung Soo Ahn, Kwang Sik Yoon, Byoung Jin Ahn, Jin Shin, An Chul Chung, Young Joong Cho, Hong Woo Nahm; J Korean Endocr Soc. 1998;13(1):45-51. Published online January 1, 2001

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Abstract PDF: BACKGROUND
An increase in oxidative stress has been suggested to play major roles in the complications of diabetes. The bulk of the experimental data favors enhanced free radicals in diabetes and antioxidant defense mechanisms may be reduced in diabetes. Melatonin, the major secretory product of the pineal gland has been shown to be a potent and specific hydroxyl radical scavenger. The purpose of our study was to determine the antioxidative effeet of melatonin in streptozotocin-induced diabetic rats. METHODS: Sprague-Dawley rats weighing 200-240 g were divided into 3 groups: normal controls(n-7), diabetic contmls(n-9), melatonin-treated diabetic animals(n-9). Diabetes was induced by intraperitoneal injection of streptozotoein(55 mg/kg body weight) and melatonin(6 mg/kg body weight) was orally administered for 20 days. At day 20 after streptozotocin administration, blood was collected for the assay of glucose, albumin and cholesterol. Erythrocyte membrane lipid peroxidation was determined by malonyldialdehyde(MDA) reactivity. RESULTS: 1) The MDA resctivity of erytbrocyte membrane in melatonin-treated diabetic animals (meanstandard deviation: 5.52+-1.52nmol/ml packed cells) were lower(p<0.05) than that in diabetic controls(7.68+-1.16nmol/mL packed cells). But, there was no significant difference between melatonin-treated diabetic animals and normal contls(4.93+-1.19 nmol/mL packed cells). 2) There were no significant differences of blood glucose and body weight between diabetic controls and melatonin-treated diabetic animals. CONCLUSION: These results show the antioxidative effect of melatonin in streptozotocin-induced diabetic rats. Further clinical and long-term experimental studies are needed to assess the effect of melatonin on development and progression of diabetic complications.

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