• Journal of Ginseng Research
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• 제41권4호
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• pp.503-512
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• 2017

Background: Chronic heavy alcohol consumption may raise the risk of developing type 2 diabetes mellitus. Saponins inhibit apoptosis of pancreatic islet cells and reduce lipid parameters. The present study was designed to investigate the effect of saponin on chronic ethanol-treated diabetic rats. Methods: Long-Evans Tokushima Fatty (LETO) and Otsuka Long-Evans Tokushima Fatty (OLETF) rats were pair-fed a Lieber-DeCarli diet with and without 5% ethanol for 12 wks. Two weeks after starting the pair-feeding with the Lieber-DeCarli diet, intraperitoneal injection of saponin was performed for 10 wks. To perform the experiments, rats were divided as follows: LETO-Control (LC), LETO-Ethanol (LE), LETO-Ethanol-Saponin (LES), OLETF-Control (OC), OLETF-Ethanol (OE), and OLETF-Ethanol-Saponin (OES). Results: The weights of epididymal and mesenteric fat tissue in LES and OES rats were the lightest from among the LETO and OLETF groups, respectively. The secretion of alanine aminotransferase and cholesterol in OES rats decreased significantly compared to their secretion in OC and OE rats, respectively. The islets of the pancreas in LE and OE rats showed clean, unclear, and smaller morphology compared to those of LC, LES, OC, and OES rats. In addition, the expression of insulin in the islets of the pancreas in LC, LES, OC, and OES rats was higher than in LE and OE rats. Conclusion: Saponin may not only be helpful in alleviating the rapid progress of diabetes due to chronic alcohol consumption in diabetic patients, but may also show potential as an antidiabetic drug candidate for diabetic patients who chronically consume alcohol.

• Molecules and Cells
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• 제47권1호
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• pp.100004.1-100004.11
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• 2024

Insulin is essential for maintaining normoglycemia and is predominantly secreted in response to glucose stimulation by β-cells. Incretin hormones, such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide, also stimulate insulin secretion. However, as obesity and type 2 diabetes worsen, glucose-dependent insulinotropic polypeptide loses its insulinotropic efficacy, whereas GLP-1 receptor (GLP-1R) agonists continue to be effective owing to its signaling switch from Gs to Gq. Herein, we demonstrated that endoplasmic reticulum (ER) stress induced a transition from Gs to Gq in GLP-1R signaling in mouse islets. Intriguingly, chemical chaperones known to alleviate ER stress, such as 4-PBA and TUDCA, enforced GLP-1R's Gq utilization rather than reversing GLP-1R's signaling switch induced by ER stress or obese and diabetic conditions. In addition, the activation of X-box binding protein 1 (XBP1) or activating transcription factor 6 (ATF6), 2 key ER stress-associated signaling (unfolded protein response) factors, promoted Gs utilization in GLP-1R signaling, whereas Gq employment by ER stress was unaffected by XBP1 or ATF6 activation. Our study revealed that ER stress and its associated signaling events alter GLP-1R's signaling, which can be used in type 2 diabetes treatment.

• 생명과학회지
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• 제18권11호
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• pp.1584-1591
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• 2008

클로렐라의 생리활성작용 중 인슐린작용 활성 및 항당뇨효능이 보고된 바 있으나 클로렐라 열수 추출물(Chlorella hot water extract, CE)에 의한 혈당치 조절에 관한 연구는 보고된 바 없다. 따라서 본 실험에서는 실험적인 당뇨유발물질 streptozotocin (STZ)을 성장기 SD계 수컷 흰쥐에 단회 복강 주사하여 당뇨를 유발시킨 CE 무첨가 STZ-Control군, CE 3% 첨가 STZ+CE3군 및 CE 6% 첨가 STZ+CE6군, 그리고 정상군(Normal군)으로 실험 설계하여 4주간 식이와 함께 물을 자유 급여하였다. 공복 및 비공복시 혈당치는 정상군보다 당뇨 대조군에서 현저히 증가하여 당뇨 유발이 확인되었고, 이러한 혈당치 증가는 클로렐라 열수 추출물 분말 3% 첨가 STZ+CE3군 및 6% 첨가 STZ+CE6군에서 각각 감소하였다. 혈중 인슐린 농도는 당뇨 대조군에서 낮게 나타났으나 클로렐라 열수 추출물 분말 첨가식이 투여군들에서 인슐린 농도 감소현상이 상쇄되었다. 또한 정상군보다 STZ- 당뇨 대조군에서 Fructosamine 및 뇨당이 증가하였으나, 클로렐라 추출물 투여 STZ+CE3군 및 STZ+CE6군에서 감소하는 경향을 나타내었고, 특히 이러한 효과는 클로렐라 열수 추출물 첨가농도 의존적이었다. 클로렐라 추출물 투여군에서 혈당치 감소의 기작을 검토하기 위하여 인슐린 합성과 분비에 관여하는 췌장의 췌도 베타세포의 면역반응에 의한 조직검사에서 정상군의 정상적인 둥근 모양의 형태를 잘 유지하고 있었으나, STZ-당뇨 대조군에서는 베타세포가 심하게 파괴되어 극소수 존재함으로서 면역 반응성이 매우 미약하였다. 그러나 클로렐라 열수 추출물 투여군에서 농도 의존적으로 베타세포가 많아지면서 정상군과 비슷한 췌도 세포의 형태를 유지하고 있었다. 클로렐라 열수 추출물은 STZ 에 의해 파괴된 베타세포를 회복시키는 효능이 강한 것으로 보여 진다. 이러한 결과는 클로렐라 열수 추출물에 의해 인슐린을 생산해 내는 췌도 베타세포가 회복됨에 따라 인슐린 증강 작용으로 혈당치 강하 효과가 실험 동물을 통하여 확인되었다.

• 생명과학회지
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• 제16권5호
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• pp.767-772
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• 2006

Sprague-Dawley 수컷에 streptozotocin (50 mg/kg body weight)을 복강 주사하여 유발시킨 당뇨군에서 베타인(1%, w/w) 첨가에 의한 항당뇨 및 간보호 효과를 검토하였다. Streptozotocin-유발 당뇨군에서 혈당치 및 fructosamine 농도가 현저히 증가하였고, 이러한 증가는 베타인 투여로 감소하였다. 간 기능의 biomarker로 사용되는 alanine aminotransferase (AST) 및 aspartate aminotransferase (ALT) 활성은 당뇨군에서 현저히 증가한 반면 간보호 효과가 있는 베타인 투여 당뇨군에서는 정상군 수준으로 회복됨으로써 당뇨성 간 손상에 효과가 있는 것으로 나타났다. 혈중 중성지질 농도는 당뇨군에서 현저히 증가하였으나, 베타인 투여에 의해 정상군 수준까지 감소하였으나, 총 콜레스테롤 농도는 베타인 첨가에 의해 증가하였다. 췌장 조직의 조직검사에서 췌도 세포의 정상적인 타원형 모양이 정상군에서는 잘 유지되었으나, Streptozotocin-유발 당뇨군에서는 췌도 세포의 파괴가 일어났으며, 베타인 투여에 의해서는 회복된 것으로 나타났다. 이상의 결과로 볼 때 당뇨군에서 베타인 투여에 의한 혈당강하 효과는 췌장의 췌도세포 파괴 억제에 의한 것으로 시사되었다.

• 대한수의학회지
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• 제41권2호
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• pp.133-138
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• 2001

부란 1일부터 부화직후까지의 닭 태자 췌장에서 serotonin 면역반응세포들의 부위별 분포 및 상대적 빈도를 면역조직화학적 방법으로 검색하였다. 췌장은 해부학적으로 배쪽, 등쪽, 제 3엽 및 비장엽의 4개엽으로 구분하였으며, 각 엽은 조직학적으로 외분비 부분, light 및 dark 췌장섬의 3부분으로 세분하였다. 이들의 각 발생단계에 따른 닭 췌장에서 serotonin 면역반응세포들의 분포 및 빈도는 췌장의 엽, 조직학적 부위 및 발생단계에 따라서 매우 다양하게 관찰되었으나, 대체로 원형 또는 난원형의 형태로 모든 엽에서 관찰되었다. 외분비 부분에서 serotonin 면역반응세포들은 비장엽의 경우 부란 13일과 14일에서만 국한되어 관찰되었고, 제 3엽에서는 부란 10일부터 부란 19일 동안 관찰되었다. 또한 배쪽엽에서는 부란 10일부터 부화 직후까지 관찰되었으며, 등쪽엽에서는 부란 11일부터 부화 직후까지 관찰되었다. 췌장섬에서 이들 면역반응세포는 비장엽의 dark 췌장섬에서만 부란 15일과 부란 16일에 국한되어 극소수 관찰되었고 다른 엽 또는 light 췌장섬에서는 관찰되지 않았다. 결론적으로 serotonin 면역반응세포들은 부란 발생 초기에는 다수 관찰된 이후 발생단계에 따라 점차적으로 감소되며 이런 양상은 엽의 종류에 관계없이 나타나는 것으로 관찰되었다.

• BMB Reports
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• 제48권3호
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• pp.172-177
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• 2015

Upregulation of pro-inflammatory mediators contributes to ${\beta}$-cell destruction and enhanced infiltration of immune cells into pancreatic islets during development of type 1 diabetes mellitus. In this study, we examined the regulatory effects and the mechanisms of action of celastrol against cytotoxicity and pro-inflammatory immune responses in the RINm5F rat pancreatic ${\beta}$-cell line stimulated with a combination of interleukin-1 beta, tumor necrosis factor-alpha, and interferon-${\gamma}$. Celastrol significantly restored cytokine-induced cell death and significantly inhibited cytokine-induced nitric oxide production. In addition, the protective effect of celastrol was correlated with a reduction in pro-inflammatory mediators, such as inducible nitric oxide synthase, cyclooxygenase-2, and CC chemokine ligand 2. Furthermore, celastrol significantly suppressed cytokine-induced signaling cascades leading to nuclear factor kappa B (NF-${\kappa}B$) activation, including $I{\kappa}B$-kinase (IKK) activation, $I{\kappa}B$ degradation, p65 phosphorylation, and p65 DNA binding activity. These results suggest that celastrol may exert its cytoprotective activity by suppressing cytokine-induced expression of pro-inflammatory mediators by inhibiting activation of NF-${\kappa}B$ in RINm5F cells.

• Animal cells and systems
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• 제13권1호
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• pp.17-23
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• 2009

In previous studies, we found that Annexin I (Anx I) was co-secreted with insulin in response to glucose, and that extracellular Anx I stimulated the release of insulin via the Anx I binding site in rat pancreatic islets and the &-cell line. However, the role that Anx I plays in the insulin secretion was not established. Therefore, in this study, we evaluated the insulin secretion pattern in response to Anx I and the involvement of the cytoskeleton or PKC in Anx Istimulated insulin secretion in MIN6N8a cells. The peak time of insulin secretion in response to Anx I treatment corresponded with the second phase insulin secretion by glucose in the perifused pseudoislets. In addition, Anx I-stimulated insulin secretion was not affect by readily releasable pool depletion. Taken together, these findings indicate that Anx I treatment was associated with movement of the reserve pool of insulin. Furthermore, Anx I-stimulated insulin secretion was attenuated by treatment with a microfilament inhibitor, cytochalasin B, as well as by PKC down regulation. These results indicate that Anx I may be a regulator of second phase insulin secretion.

• Advances in Traditional Medicine
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• 제5권2호
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• pp.160-166
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• 2005

The present study was carried out to investigate the hypoglycemic effect of a polyherbal aqueous extract (Curcuma longa Linn., Emblica officinalis Gaertn., Trigonella foenum-graecum Linn., Enicostemma littorale Blume) in alloxan-induced diabetic rats. Short term experiments showed a decrease in blood glucose levels at $2^{nd}\;hr$ of administration of the aqueous extract in alloxan-induced diabetic rats with increase in serum insulin levels. The extract did not show any effect on blood glucose or serum insulin levels in normoglycaemic rats. Treatment with the extract (1.5 g dry plant equivalent extarct/100 g body weight/day) for 20 days in diabetic rats showed a significant decrease in blood glucose and glycosylated haemoglobin levels and an increase in serum insulin levels. The aqueous extract also showed an enhanced glucose-induced insulin release at 11.1 mM glucose from isolated rat pancreatic islets. The extract did not show any toxicity at the particular dose used.

• 대한의생명과학회지
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• 제24권4호
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• pp.311-318
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• 2018

Vitamin C (ascorbic acid) supplementation has been suggested to negatively correlate with obesity in humans and other animals. Previous studies, including ours, have demonstrated that a high-fat diet (HFD) induces obesity and related diseases such as hyperlipidemia, hyperglycemia, insulin resistance, and nonalcoholic fatty liver disease. Here, we investigated the effects of vitamin C on visceral adipocyte hypertrophy and glucose intolerance in C57BL/6J mice. Mice received a low-fat diet (LFD, 10% kcal fat), HFD (45% kcal fat), or the same HFD supplemented with vitamin C (HFD-VC, 1% w/w) for 15 weeks. Visceral adiposity and glucose intolerance were examined using metabolic measurements, histology, and gene expression analyses. Mice in the HFD-VC supplementation group had reduced body weight, mesenteric fat mass, and mesenteric adipocyte size compared with HFD-fed mice. Vitamin C intake in obese mice also decreased the mRNA levels of lipogenesis-related genes (i.e., stearoyl-CoA desaturase 1 and sterol regulatory element-binding protein 1c) in mesenteric adipose tissues, inhibited hyperglycemia, and improved glucose tolerance. In addition, vitamin C attenuated the HFD-induced increase in the size of pancreatic islets. These results suggest that vitamin C suppresses HFD-induced visceral adipocyte hypertrophy and glucose intolerance in part by decreasing the visceral adipose expression of genes involved in lipogenesis.

• 비만대사연구학술지
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• 제3권1호
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• pp.35-42
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• 2024

Serotonin, a biogenic amine widely found in many organisms, functions as both a neurotransmitter and hormone. Although serotonin is involved in various physiological processes, this study aimed to review its role in energy metabolism. Given that serotonin cannot cross the blood-brain barrier and is synthesized by two different isoforms of tryptophan hydroxylase in the central nervous system (CNS) and peripheral tissues, it is reasonable to assume that serotonin in the CNS and peripheral tissues functions independently. Recent studies have demonstrated how serotonin influences energy metabolism in metabolic target organs such as the intestines, liver, pancreas, and adipose tissue. In summary, serotonin in the CNS induces satiety and appetite suppression, stimulates thermogenesis, and reduces body weight. Conversely, serotonin in the periphery increases intestinal motility, stimulates gluconeogenesis in the liver, suppresses glucose uptake by hepatocytes, promotes fat uptake by liver cells, stimulates insulin secretion while suppressing glucagon secretion in the pancreatic islets, promotes lipogenesis in white adipose tissue, inhibits lipolysis and browning of white adipose tissue, and suppresses thermogenesis in brown adipose tissue, thereby storing energy and increasing body weight. However, considering that most experimental results were obtained using mice and conducted under specific nutritional conditions, such as high-fat diets, whether serotonin acts in the same way in humans, whether it will act similarly in individuals with normal versus obese weights, and whether its effects vary depending on the type of food consumed, remain unknown.