• 제목/요약/키워드: Insulin secretion

검색결과 290건 처리시간 0.035초

HD047703, a New Promising Anti-Diabetic Drug Candidate: In Vivo Preclinical Studies

  • Kim, SoRa;Kim, Dae Hoon;Kim, Young-Seok;Ha, Tae-Young;Yang, Jin;Park, Soo Hyun;Jeong, Kwang Won;Rhee, Jae-Keol
    • Biomolecules & Therapeutics
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    • 제22권5호
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    • pp.400-405
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    • 2014
  • G-protein coupled receptor 119 (GPR119) has emerged as a novel target for the treatment of type 2 diabetes mellitus. GPR119 is involved in glucose-stimulated insulin secretion (GSIS) from the pancreatic b-cells and intestinal cells. In this study, we identified a novel small-molecule GPR119 agonist, HD047703, which raises intracellular cAMP concentrations in pancreatic ${\beta}$-cells and can be expected to potentiate glucose-stimulated insulin secretion from human GPR119 receptor stably expressing cells (CHO cells). We evaluated the acute efficacy of HD047703 by the oral glucose tolerance test (OGTT) in normal C57BL/6J mice. Then, chronic administrations of HD047703 were performed to determine its efficacy in various diabetic rodent models. Single administration of HD047703 caused improved glycemic control during OGTT in a dose-dependent manner in normal mice, and the plasma GLP-1 level was also increased. With respect to chronic efficacy, we observed a decline in blood glucose levels in db/db, ob/ob and DIO mice. These results suggest that HD047703 may be a potentially promising anti-diabetic agent.

Chronic saponin treatment attenuates damage to the pancreas in chronic alcohol-treated diabetic rats

  • Choi, Mi Ran;Kwak, Su Min;Bang, Sol Hee;Jeong, Jo-Eun;Kim, Dai-Jin
    • 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.

Effect of Propofol, an Intravenous Anesthetic Agent, on $K_{ATP}$ Channels of Pancreatic ${\beta}-cells$ in Rats

  • Park, Eun-Jee;Song, Dae-Kyu;Cheun, Jae-Kyu;Bae, Jung-In;Ho, Won-Kyung;Earm, Yung-E
    • The Korean Journal of Physiology and Pharmacology
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    • 제4권1호
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    • pp.25-31
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    • 2000
  • ATP-sensitive potassium channels ($K_{ATP}$ channels) play an important role in insulin secretion from pancreatic beta cells. We have investigated the effect of propofol on $K_{ATP}$ channels in cultured single pancreatic beta cells of rats. Channel activity was recorded from membrane patches using the patch-clamp technique. In the inside-out configuration bath-applied propofol inhibited the $K_{ATP}$ channel activities in a dose-dependent manner. The half-maximal inhibition dose (ED50) was $48.6{\pm}8.4\;{\mu}M$ and the Hill coefficient was $0.73{\pm}0.11.$ Single channel conductance calculated from the slope of the relationship between single channel current and pipette potential $(+20{\sim}+100\;mV)$ was not significantly altered by propofol $(control:\;60.0{\pm}2.7\;pS,\;0.1\;mM\;propofol:\;58.7{\pm}3.5\;pS).$ However, mean closed time was surely increased. Above results indicate that propofol blocks the $K_{ATP}$ channels in the pancreatic beta cells in the range of its blood concentrations during anesthesia, suggesting a possible effect on insulin secretion and blood glucose level.

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Supplementation of a Novel Microbial Biopolymer, PGB1, from New Enterobacter sp. BL-2 Delays the Deterioration of Type 2 Diabetic Mice

  • Yeo, Ji-Young;Lee, Yong-Hyun;Jeon, Seon-Min;Jung, Un-Ju;Lee, Mi-Kyung;Jung, Young-Mi;Choi, Myung-Sook
    • Journal of Microbiology and Biotechnology
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    • 제17권12호
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    • pp.1983-1990
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    • 2007
  • Antidiabetic effects of a novel microbial biopolymer (PGB) 1 excreted from new Enterobacter sp. BL-2 were tested in the db/db mice. The animals were divided into normal control, rosiglitazone (0.005%, wt/wt), low PGB1 (0.1%, wt/wt), and high PGB1 (0.25%, wt/wt) groups. After 5 weeks, the blood glucose levels of high PGB1 and rosiglitazone supplemented groups were significantly lower than those of the control group. In hepatic glucose metabolic enzyme activities, the glucokinase activities of PGB1 supplemented groups were significantly higher than the control group, whereas the PEPCK activities were significantly lower. The plasma insulin and hepatic glycogen levels of the low and high PGB1 supplemented groups were significantly higher compared with the control group. Specifically, the insulin and glycogen increases were dose-responsive to PGB1 supplement. PGB1 supplement did not affect the IPGTT and IPITT compared with the control group; however, rosiglitazone significantly improved IPITT. High PGB1 and rosiglitazone supplementation preserved the appearance of islets and insulin-positive cells in immunohistochemical photographs of the pancreas compared with the control group. These results demonstrated that high PGB1 (0.25% in the diet) supplementation seemingly contributes to preventing the onset and progression of type 2 diabetes by stimulating insulin secretion and enhancing the hepatic glucose metabolic enzyme activities.

증포 횟수를 달리하여 만든 선식을 첨가한 고지방식이가 비만 쥐의 혈당과 염증지표에 미치는 영향 (Effects of Sunsik Prepared through Steaming-Drying Cycles on Blood Glucose and Inflammatory Marker in Rats Fed High Fat)

  • 황경희;공현주;이언희;최은미;황수정;장정현;양경미
    • 동아시아식생활학회지
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    • 제25권1호
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    • pp.111-120
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    • 2015
  • This study was conducted to evaluate the effects of Sunsik prepared by steaming -drying cycles- on blood glucose and inflammatory markers in high fat diet-induced obese rats. The experimental animals were divided into five groups and subjected to diets for 8 weeks; normal diet (control), high fat diet (HF), and high fat diet+10% supplementation of Sunsik (1HF, 3HF, 7HF, 9HF). The results showed body weight, food efficiency ratio, blood glucose and insulin levels of high fat diet groups were significantly higher than those of the control group. Increased glucose levels by high fat diet were reduced to normal levels by the four Sunsik supplementations. Insulin resistance (HOMA-IR) of the HF group was significantly higher than those of the control group, whereas supplementation with the four types of Sunsik reduced insulin resistance to similar levels as the control group. Increased insulin secretion and leptin levels of high fat diet-induced obese rats were significantly reduced by supplementation with the four types of Sunsik. C-reactive protein (CRP) of inflammation related components was significantly higher than the control group. However, increased CRP concentration by high fat diet was significantly reduced by supplementation with Sunsik.

사립체 근병증 환자에서 발생한 자가항체 양성의 당뇨병성 케톤산증 1례 (A Patient with Mitochondrial Myopathy who Experienced Diabetic Ketoacidosis with Auto-antibody)

  • 남순영;허림;권영희;이지은;조성윤;진동규
    • 대한유전성대사질환학회지
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    • 제14권2호
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    • pp.191-194
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    • 2014
  • 사립체 근병증은 사립체 호흡 사슬의 장애로 인한 것으로 내분비계 관련 증상이 흔히 동반되고 그 중 당뇨병이 상대적으로 높은 빈도를 보인다고 알려져 있다. 사립체 근병증에서의 당뇨병은 사립체 기능 장애로 인한 인슐린 분비의 결함으로 발생하고, 대개 인슐린 의존성이나 당뇨병성 케톤산증으로 발현하거나 자가 항체가 검출되는 경우는 드물다. 저자들은 사립체 근병증 환자에서 당뇨병성 케톤산증으로 발현하고 Anti-GAD antibody와 Anti-insulin auto-antibody가 모두 양성으로 확인된 인슐린 의존성 당뇨병을 진단하였기에 이를 기존의 문헌과 비교하여 보고하는 바이다.

Insulin 측정용 방사면역측정법 시약의 평가 (The Evaluation of Radioimmunoassay kits for Insulin)

  • 신용환;김윤현;이일규;김지영;석재동;신숙희
    • 핵의학기술
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    • 제16권2호
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    • pp.149-155
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    • 2012
  • 혈중 Insulin 농도는 췌장 ${\beta}$세포의 인슐린 분비기능을 반영하고 당뇨병의 진단, 병태 파악, 내당능 이상의 원인감별에 유용한 지표이다. 핵의학검사실에서 사용하고 있는 혈중 Insulin 측정용 시약들은 제조회사마다 검사방법 뿐만 아니라 비용효과 측면, 정밀도 등 정도관리 측면에서도 다소 차이를 보이고 있다. 따라서 Insulin 측정용 방사면역측정법 시약들의 제조 회사별 비교를 통해 진단적 성능을 평가하고자 본 연구를 시행하였다. 2009년 8월 59명의 환자 검체를 대상으로 시행된 3개 제조회사(Biosource, Siemens, TFB)의 혈중 Insulin측정치와 2011년 12월 68명의 환자 검체를 대상으로 시행된 4개 제조회사(Immunotech, Izotope, BNIBT, Cisbio)의 혈중 Insulin측정치를 비교 평가하였다. 이들 7개 제조회사별 Insulin측정치에 대하여 정밀도, 회수율, 상관관계를 살펴보았으며 일부 인슐린 고농도 특이검체를 가지고 희석시험을 통해 혈중 Insulin측정치를 상호 비교 평가하였다. 혈중 Insulin 측정은 시약 내 설명서의 권고사항을 준수하여 실시하였으며 결과 검증을 위한 통계 프로그램은 SPSS 12.0을 이용하였다. 측정 내 정밀도는 Biosource, Siemens, TFB, Immunotech, Izotope, BNIBT, Cisbio 7개 제조회사 모두 5.0% 이하의 변이계수를 보였다. 회수율은 저, 중, 고 세가지 농도의 혈청에서 Biosource, Siemens, TFB시약이 각각 94.2~103.7%, 99.0~104.6%, 99.7~107.6% 구간을 보였고 Immunotech, Izotope, BNIBT, Cisbio 시약에서 각각 93.5~99.1%, 91.4~99.1%, 99.2~131.0%, 84.8~102.3% 구간의 회수율을 보였다. Biosource 시약을 기준으로 비교한 상관관계에서 Siemens 시약이 R2=0.96(P<0.01), TFB시약이 R2=0.99(P<0.01)를 보였으며 TFB 시약을 기준으로 비교한 상관관계에서는 BNIBT시약(R2=0.80, P<0.01)을 제외한 대부분의 시약에서 강한 상관관계(R2=0.96 이상, p<0.01)를 보였다. 200 ${\mu}IU/ml$ 이상 고농도 희석시험에서는 당뇨병환자 검체를 대상으로 했을 때 7개 제조회사 시약 모두 고농도값을 정상적으로 측정하였다. 하지만, 인슐린 종양 검체를 대상으로 측정한 검사에서는 TFB, Siemens, Izotope, Cisbio시약들은 고농도값을 정상적으로 측정하였지만 Biosource와 Immunotech 시약에서 각각 47.4 ${\mu}IU/ml$, 72.3 ${\mu}IU/ml$의 측정치를 보였다. 혈중 Insulin 측정용 방사면역측정법 시약들은 전반적으로 성능이 임상 적용 가능한 범위의 측정 정밀도를 보이면서, 우수한 회수율과 양호한 상관관계를 보였지만 일부 시약에서 고농도 특이검체를 대상으로 Insulin을 측정한 검사에서 고농도값을 제대로 측정하지 못했다. 따라서 여러가지 요인을 놓고 볼 때 비용 효과측면과 자동화 장비에 대한 호환성, 검사 반응시간등 각 검사실 환경에 맞는 시약과 진단적 성능이 보다 우수한 시약을 선정하여 사용한다면 정확하고 신속한 결과보고에 있어서 많은 도움이 된다고 사료된다.

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배양된 이자섬 $\beta$세포의 미세구조적 변화와 인슐린 분포 양상 (Ultrastructural Change and Insulin Distribution of the Cultured Pancreatic Islet $\beta$-cell)

  • 민병훈;김수진
    • Applied Microscopy
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    • 제37권4호
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    • pp.249-258
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    • 2007
  • 이자섬은 이자를 구성하는 외분비조직에 둘러싸여 존재하는 내분비세포의 집단으로, 이자섬에서 분비되는 인슐린은 $\beta$세포에서 분비되는 호르몬이며, 세포질의 리보좀에서 합성되고 골지체를 경유하여 세포질로 방출되는 기작을 가지고 있다. 충분한 양의 이자섬 이식은 인슐린 의존형 당뇨병인 제1형 당뇨병에서 정상혈당을 회복시키고, 당뇨 합병증을 방지할 수 있는 치료방법으로 사용되고 있다. 하지만 당뇨병 환자에게 이식을 위한 이자섬의 양에 비해 공여자로부터 증여된 이자섬의 양은 제한적이다. 이러한 문제점은 이자섬의 증식으로 연구되고 있으나, 배양된 이자섬이 정상 조직내의 이자섬과 형태적 기능적으로 동일한 것인지에 관한 연구는 미비하였다. 따라서 본 연구에서는 분리된 이자섬과 배양된 이자섬을 구성하는 세포들의 내부구조의 변화를 주사전자현미경, 투과전자현미경을 이용하여 세포의 미세구조를 확인하고, 인슐린 항체를 이용한 $\beta$세포 내의 인슐린 분포양상을 확인하여 다음과 같은 결과를 얻었다. 분리된 이자섬의 $\beta$세포는 일반적인 핵 미토콘드리아, 세포질세망 그리고 인슐린 과립이 분포하고, 배양된 이자섬 $\beta$세포의 경우 분리된 이자섬에 비하여 일반적인 핵의 모습과 부피가 증가한 세포질과 미토콘드리아, 세포질세망 그리고 골지체의 발달이 이루어지는 것으로 관찰되었다. 인슐린 과립의 경우 분리된 이자섬에 비해 감소하며, 세포막 주위에 분포하는 것으로 관찰되었다. 배양된 이자섬에서 관찰되는 인슐린 과립 분포의 변화, 세포질세망의 증가, 골지체의 발달은 배양된 이자섬 $\beta$세포의 인슐린 생성 분비 기능의 향상과 부피의 증가가 이루어지기 위한 세포 내부의 형태적 변화가 이루어지는 것으로 추측된다.

Hypoglycemic Effect of Exo- and Endo-biopolymers Produced by Submerged Mycelial Culture of Ganoderma lucidum in Streptozotocin-Induced Diabetic Rats

  • Yang, Byung-Keun;Michael A Wilson;Cho, Kai-Yip;Song, Chi-Hyun
    • Journal of Microbiology and Biotechnology
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    • 제14권5호
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    • pp.972-977
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    • 2004
  • The hypoglycemic effect of an exo-biopolymer (EXO) and endo-biopolymer (ENDO) produced from submerged mycelial culture of Ganoderma lucidum was investigated in streptozotocin (STZ)-induced diabetic rats. Both the EXO and ENDO showed hypoglycemic potential, however, the former proved to be more potent than the latter. The administration of the EXO at the dose of 100 mg/kg body weight (BW) significantly reduced the plasma glucose level (23.5%) and increased the plasma insulin level (2.2 fold) in the diabetic animals. The EXO also lowered the plasma total cholesterol, triglyceride, low-density lipoprotein (LDL) cholesterol, and athrogenic index by 14.7, 31.4, 24.1, and 45.4%, respectively, and reduced the liver total cholesterol and triglyceride levels by 6.7 and 25.8%, respectively. It increased the plasma high-density lipoprotein (HDL) cholesterol (37.7%), compared to the control group. Furthermore, the alanine transaminase (ALT) and aspartate transaminase (AST) showed lower activities in the EXO administered groups than the other experimental groups. Taken together, these results suggest that the exo-biopolymer may alleviate the blood glucose level by increased insulin secretion.

한양방협진으로 호전된 당뇨병 환자 1례 (A Case of Diabetes Mellitus Treated with Oriental and Western Medical Combination Theraphy)

  • 박송기;권은희;송광규;전귀옥;신현철;강석봉;문정환
    • 대한한방내과학회지
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    • 제25권3호
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    • pp.602-608
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    • 2004
  • Diabetes mellitus is a metabolic disorder characterized by hyperglycemia which results from one or both of decreased insulin secretion and increased insulin resistance. Chronic hyperglycemia causes damage to the eyes, kidneys, nerves, heart and blood vessels. The major goal in treating diabetes mellitus is controlling elevated blood sugars without causing abnormally low levels of blood sugar. A 67-year-old woman was admitted with hyperglycemia, thirst, Lt. leg numbness and both leg weakness. The patient was diagnosed as So-gal(消渴) due to dry ness-heat based on yin-deficiency(陰虛燥熱) through oriental medicine and NIDDM through western medicine. The patient was treated with oriental and western medicines. Specifically herbal medicine(Gamijihwangtang), acupuncture, moxa theraphy were used as well as oral medications. Clinical symptoms improved and hyperglycemia dramatically stablized.

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