• 대한한의학회지
• /
• 제22권4호
• /
• pp.79-89
• /
• 2001

Objectives : This study has been carried out to investigate the effects of the Saengjinyanghyutang-gamibang and Rosa rugosa extracts on pancreas of the hyperglycemia mice induced with streptozotocin. Methods : We examined immunohistochemistry for insulin and COX-2, ultrastructural changes of acini by electron microscope, and changes of the blood glucose and BUN levels. Results : The ${\beta}-cells$ on Langerhnan's islet were destructed by administration of streptozotocin, so that few insulin-positive cells were observed in the control group. However, a lot of insulin-positive cells were observed in the experimental groups. These cells had recovered from the damage. As a result of COX-2 immunostain, COX-2 expression were highest in the control group other than the Saengjinyanghyutang-gamibang and Rosa rugosa extracts administered groups. As the electron microscopical observation, the centroacinar cells and acini of pancreas were destructed or damaged by administration of streptozotocin in the control group, but these recovered !Tom the damage in the other experimental groups. The levels of serum glucose were decreased remarkably on the Rosa rugosa and Saengjinyanghyutang-gamibang extracts administered groups compared with control group. Conclusions : These results suggest that administration of the Rosa rugosa and Saengjinyanghyultang-gamibang extracts to the mice reduced the damage induced by streptozotocin.

• Molecules and Cells
• /
• 제40권5호
• /
• pp.371-377
• /
• 2017

Despite the importance of the receptor activator of nuclear factor (NF)-kappaB ligand (RANKL)-RANK signaling mechanisms on osteoclast differentiation, little has been studied on how RANK expression is regulated or what regulates its expression during osteoclastogenesis. We show here that insulin signaling increases RANK expression, thus enhancing osteoclast differentiation by RANKL. Insulin stimulation induced RANK gene expression in time- and dose-dependent manners and insulin receptor shRNA completely abolished RANK expression induced by insulin in bone marrow-derived monocyte/macrophage cells (BMMs). Moreover, the addition of insulin in the presence of RANKL promoted RANK expression. The ability of insulin to regulate RANK expression depends on extracellular signal-regulated kinase 1/2 (ERK1/2) since only PD98059, an ERK1/2 inhibitor, specifically inhibited its expression by insulin. However, the RANK expression by RANKL was blocked by all three mitogen-activated protein (MAP) kinases inhibitors. The activation of RANK increased differentiation of BMMs into tartrate-resistant acid phosphatase-positive ($TRAP^+$) osteoclasts as well as the expression of dendritic cell-specific transmembrane protein (DC-STAMP) and d2 isoform of vacuolar ($H^+$) ATPase (v-ATPase) Vo domain (Atp6v0d2), genes critical for osteoclastic cell-cell fusion. Collectively, these results suggest that insulin induces RANK expression via ERK1/2, which contributes to the enhancement of osteoclast differentiation.

• Anatomy and Cell Biology
• /
• 제56권1호
• /
• pp.122-136
• /
• 2023

Depression is a prevalent global problem since ages, predominately treated with SSRI. Cipralex, is an antidepressant of the SSRIs class used as a remedy for mood, depression and anxiety. Silymarin (SIL), a natural free radical scavenging, has an antioxidant and anti-inflammatory properties. This hypothesis evaluates, for the first time, the role of cipralex on the structure of the endocrine and exocrine components of the pancreas and assess the beneficial effects of SIL on these changes. Forty-five rats were divided into control, cipralex, and cipralex plus SIL groups. During sacrifice, all rats and pancreases were weighed and the ratio of pancreatic weight (PW) to rat weight (RW) was calculated, blood samples were collected to estimate fasting glucose, insulin and amylase levels, the specimens were prepared for histological, immunohistochemical (inducible nitric oxide synthase [iNOS], tumour necrosis factor-alpha [TNF-α], caspase 3, proliferating cell nuclear antigen [PCNA], and anti-insulin antibody), and morphometrical studies. Cipralex group exhibited marked destruction of the pancreatic architecture of the exocrine and endocrine parts, with a dense collagen fiber deposition. Also, there is highly significant decrease (P<0.001) of PW/RT ratio, insulin, and amylase levels, the number and diameter of islets of Langerhans, the number of PCNA positive immunoreactive cells, and the number of insulin positive β-cells. Furthermore, a highly significant increase of glucose level, iNOS, TNF-α, and caspase-3 positive immunoreactive cells in the islets of Langerhans and acinar cells were observed. SIL improves the pancreatic histological architecture, weight loss, biochemical, and immunohistochemical analyses. Administering SIL is advantageous in managing cipralex induced pancreatic injury via its anti-inflammatory, antioxidant, and anti-apoptotic qualities.

• 한국식품영양과학회지
• /
• 제33권7호
• /
• pp.1133-1138
• /
• 2004

본 연구는 streptozotocin(STZ)을 투여하여 고혈당이 유발된 생쥐(UM군)에 생지황(Rhemanniae Radix) 전탕액의 투여(5.0 mL/kg/day, RR군)효과를 밝히기 위하여 수행하였다. STZ로 유발된 생쥐에 생지황 전탕액을 6주 동안 구강 투여한 후 혈당과 당내성 검사 및 췌장섬의 면역조직화학 검사를 하였다. 혈당수준은 RH군이 HM군에 비하여 2, 3, 5, 6주에서 유의성 있게 낮았으며, 당내성 검사 또한 RR군이 HM군에 비하여 우수한 결과를 보여 주었다. 6주 후 insulin-양성 5-세포들과 insulin-like growth factor-II 양성 물질들은 HM군에 비하여 RR군에서는 보다 높게 나타났다. HM군에서는 apoptosis 면역반응성 과립들이 췌장섬 전반에 걸쳐 관찰되었으나, RR군에서는 일부 세포들의 핵에서 면역반응성을 보여주었다. HM군에서는 대부분 췌장섬들이 파괴되어 소수 관찰되었으나 RR군은 다수 관찰되었다. 이와 같은 결과로 보아 생지황 전탕액은 STZ로 유발된 손상으로부터 췌장섬을 회복시키는 효과가 있는 것으로 사료된다.

• 동의생리병리학회지
• /
• 제26권4호
• /
• pp.497-505
• /
• 2012

To determine the effects of Banggihwanggi-tang(BGHGT) on obesity, the obesity-related factors[gastrin, calcitonin gene related peptide(CGRP), serotonin, ghrelin, obestatin, glucagon-like peptide-1(GLP-1), insulin, orexin, leptin] were investigated in the stomach, pancreas, brain of mice by immunohistochemical(IHC) methods for 4 weeks. The change of body weight was more reduced in BGHGT administered group than that of control group. The IHC density of the gastrin and CGRP positive cells on pylorus was higher in BGHGT administered group than that of control group. The number of ghrelin immunoreactive cells on stomach was lower in BGHGT administered group than that of control group. The IHC of GLP-1 positive cells did not observe in the stomach of BGHGT administered groups. The IHC density of GLP-1 in the pancreas was lower in BGHGT administered group than that of control group. The IHC density of insulin positive cells in the pancreas was lower in BGHGT administered group than that of control group. The IHC density of orexin positive neurons in the diencephalon was slightly higher in BGHGT administered group than that of control group. The IHC density of NPY and leptin positive neurons was slightly higher in BGHGT administered group than that of control group. The IHC density of serotonin positive neurons was higher in BGHGT administered group than that of control group. Therefore, we conclude that BGHGT activates appetite inhibitor through appetite related enteroendocrine cells and neuropeptides in stomach, pancreas and brain, and this activation may also be responsible for the inhibition of feeding behavior.

• 한국식품영양과학회지
• /
• 제31권6호
• /
• pp.1107-1111
• /
• 2002

배에서 추출한 phenolic compound가 streptozotocin(STZ)응 투여하고 고혈당을 유발시킨 생쥐에 미치는 영향을 밝히고자, 생쥐의 혈당, 혈중 creatinine, BUN의 변화 및 insulin-면역 조직화학적 검색과 췌장섬 $\beta$-세포의 전자현미경관찰을 통한 미세구조 변화를 관찰하였다. 실험군은 정상적인 동물 사료를 식이토록 한 대조군, 사료에 phenolic compound(PA군, 13 mg/g/kg/day; PB군,90 mg/kg/day)를 혼합하여 6주 동안 섭식하게 한 실험군으로 구분하였다. 대조군의 혈당 농도는 4주부터 높게 나타났으며, PA군의 혈당은 대조군에 비하여 유의성 (p<0.05)있게 감소하였으며, 특히 PB군에서는 4주부터 감소하기 시작하여 6주까지 유의성 (p<0.05)있게 감소하였다. BUN과creatinine의 농도는 대조군에 비하여 실험군에서 다소 감소하였으나 유의성은 없었다. STZ을 투여한 대조군의 췌장섬은 대부분 파괴되어 insulin-면역조직화학적 반응을 보인 세포들이 거의 관찰되지 않았으나, PB군에서는 다수의 췌장섬이 관찰될 뿐만 아니라 인슐린-면역조직화학 반응이 양성으로 관찰되었다. 전자현미경관찰 결과 대조군의 $\beta$-세포에서는 인슐린 함유 과립들이 소수 관찰되었으나 PB군에서는 이들 과립들이 다수 관찰되었다. 이상의 결과로 보아 phenolic compound를 섭식한 실험군 생쥐는 STZ에 의해서 손상된 췌장섬이 회복 또는 재생되어 $\beta$-세포의 인슐린 분비가 복원되 어 가고 있다고 사료되었다.

• 생명과학회지
• /
• 제33권11호
• /
• pp.859-867
• /
• 2023

루페올은 5환성 트리테르펜의 일종으로 많은 질병에 치료 효과가 있는 것으로 보고되었으나, 인슐린 저항성에 미치는 영향은 명확하지 않다. 본 연구에서는 3T3-L1 지방세포에서 루페올의 IRS-1 인산화 억제능을 통해 인슐린 저항성 개선효과를 조사하였다. 3T3-L1 세포를 배양하고 TNF-α를 24시간 동안 처리하여 인슐린 저항성을 유도하였다. 서로 다른 농도의 루페올(15, 30 μM) 또는 100 nM의 rosiglitazone을 처리한 세포를 배양한 후, 용해된 세포를 이용하여 western blotting을 시행하였다. 실험결과 루페올은 지방세포에서 TNF-α에 의해 유발되는 인슐린 신호전달의 음성 조절자와 염증 활성화 단백질 kinase에 대한 개선 효과를 나타냈다. 인슐린 신호전달의 음성 조절자인 PTP-1B와 JNK의 활성 및 IKK와 염증활성화 단백질키나아제의 활성을 억제하였다. 또한, 루페올은 IRS-1의 serine 인산화는 하향 조절하고 tyrosine 인산화는 상향 조절하였다. 그 후, 하향 조절된 PI3K/AKT 경로가 활성화되고, GLUT 4의 세포막 전위가 자극되어, 결과적으로 인슐린 저항성이 유도된 3T3-L1 지방세포에서에서 세포내 포도당 흡수가 증가하였다. 본 연구결과, 루페올은 3T3-L1 지방세포에서 인슐린 신호전달 및 염증 활성화 단백질 kinsase들의 음성 조절인자를 억제하여, IRS-1의 serine 인산화를 하향 조절함으로써 TNF-α 유발 인슐린 저항성을 개선할 수 있을 것으로 사료된다.

• Diabetes and Metabolism Journal
• /
• 제42권6호
• /
• pp.451-464
• /
• 2018

Latent autoimmune diabetes in adults (LADA) is a heterogeneous disease characterized by a less intensive autoimmune process and a broad clinical phenotype compared to classical type 1 diabetes mellitus (T1DM), sharing features with both type 2 diabetes mellitus (T2DM) and T1DM. Since patients affected by LADA are initially insulin independent and recognizable only by testing for islet-cell autoantibodies, it could be difficult to identify LADA in clinical setting and a high misdiagnosis rate still remains among patients with T2DM. Ideally, islet-cell autoantibodies screening should be performed in subjects with newly diagnosed T2DM, ensuring a closer monitoring of those resulted positive and avoiding treatment of hyperglycaemia which might increase the rate of ${\beta}-cells$ loss. Thus, since the autoimmune process in LADA seems to be slower than in classical T1DM, there is a wider window for new therapeutic interventions that may slow down ${\beta}-cell$ failure. This review summarizes the current understanding of LADA, by evaluating data from most recent studies, the actual gaps in diagnosis and management. Finally, we critically highlight and discuss novel findings and future perspectives on the therapeutic approach in LADA.

• 동의생리병리학회지
• /
• 제26권2호
• /
• pp.166-174
• /
• 2012

To determine the effects of Mahaengeuigam-tang(MHEGT) on obesity, the obesity-related factors (gastrin, CGRP, ghrelin, glucagon-like peptide-1, insulin, orexin, leptin, serotonin, NPY) were investigated in the stomach, pancreas, brain of mice by immunohistochemical methods for 4 weeks after Mahaengeuigam-tang(MHEGT) administration. The change of boy weight decreased in MHEGT administered group than that of control group. The immunohistochemical density of the gastrin and CGRP positive cells on pylorus of stomach increased in MHEGT administered group than that of control group. The number of ghrelin immunoreactive cells on stomach decreased in MHEGT administered groups than that of control group. The immunohistochemical density of GLP-1 in the pancreas decreased in MHEGT administered group than that of control group. The immunohistochemical density of insulin positive cells in the pancreas decreased in MHEGT administered group than that of control group. The immunohistochemical density of orexin and NPY positive neurons in the diencephalon was slightly stronger in MHEGT administered group than that of control group. The immunohistochemical density of serotonin and leptin positive neurons was stronger in MHEGT administered group than that of control group. These results demonstrate that Mahaengeuigam-tang(MHEGT) increased the immunohistochemical density of factors related to appetite inhibitors, and decreased the immunohistochemical density of factors related to stimulator of food intake in stomach, pancreas and brain.

• Archives of Pharmacal Research
• /
• 제27권3호
• /
• pp.324-333
• /
• 2004

To determine whether Insulin-like growth factor (IGF-I) treatment represents a potential means of enhancing the survival of cardiac muscle cells from adriamycin (ADR)-induced cell death, the present study examined the ability of IGF-I to prevent cell death. The study was performed utilising the embryonic, rat, cardiac muscle cell line, H9C2. Incubating cardiac muscle cells in the presence of adriamycin increased cell death, as determined by MTT assay and annexin V-positive cell number. The addition of 100 ng/mL IGF-I, in the presence of adriamycin, decreased apoptosis. The effect of IGF-I on phosphorylation of PI, a substrate of phosphatidylinositol 3-kinase (PI 3-kinase) or protein kinase B (AKT), was also examined in H9C2 cardiac muscle cells. IGF-I increased the phosphorylation of ERK 1 and 2 and $PKC{\;}{\zeta}{\;}kinase$. The use of inhibitors of PI 3-kinase (LY 294002), in the cell death assay, demonstrated partial abrogation of the protective effect of IGF-I. The MEK1 inhibitor-PD098059 and the PKC inhibitor-chelerythrine exhibited no effect on IGF-1-induced cell protection. In the regulatory subunit of PI3K-p85- dominant, negative plasmid-transfected cells, the IGF-1-induced protective effect was reversed. This data demonstrates that IGF-I protects cardiac muscle cells from ADR-induced cell death. Although IGF-I activates several signaling pathways that contribute to its protective effect in other cell types, only activation of PI 3-kinase contributes to this effect in H9C2 cardiac muscle cells.