N. G. Kondegowda, Xiaoying Zhang, K. Williams, A. Mozar, R. Vasavada
{"title":"Growth Factor Mediated Regulation of Beta Cell Survival","authors":"N. G. Kondegowda, Xiaoying Zhang, K. Williams, A. Mozar, R. Vasavada","doi":"10.2174/1874216501004010078","DOIUrl":"https://doi.org/10.2174/1874216501004010078","url":null,"abstract":"Numerous studies have shown that a reduction in the endogenous functional � -cell mass is a major cause of every form of diabetes. Therefore, the development of therapies to preserve and regenerate endogenous � -cell mass and function holds great promise for both Type 1 and Type 2 diabetes. The importance of understanding the mechanisms and signaling pathways regulating beta cell death is key in our ability to prolong beta cell survival in the future. One potential way to protect beta cells would be to use growth factors that can enhance their survival against different damaging insults. In this review, we describe the current knowledge on the effects of several beta cell growth factors that have been shown to increase beta cell survival in vitro and/or in vivo against varied cell death inducers. Understanding the mechanisms that mediate the pro-survival effects of these factors will enhance the potential to use these factors, or develop drugs that target their downstream pathways, as therapeutic agents for improved beta cell survival ex vivo or in vivo in the future.","PeriodicalId":88751,"journal":{"name":"The open endocrinology journal","volume":"4 1","pages":"78-93"},"PeriodicalIF":0.0,"publicationDate":"2010-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68057328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chizuko Hioki, Toshihide Yoshida, A. Kogure, K. Yoshimoto, A. Shimatsu
{"title":"Growth Hormone Administration Controls Body Composition Associated with Changes of Thermogenesis in Obese KK-Ay Mice~!2009-08-29~!2010-01-12~!2010-03-26~!","authors":"Chizuko Hioki, Toshihide Yoshida, A. Kogure, K. Yoshimoto, A. Shimatsu","doi":"10.2174/1874216501004010003","DOIUrl":"https://doi.org/10.2174/1874216501004010003","url":null,"abstract":"We investigate the effects of continuous human growth hormone (GH) therapy in young obese mice on thermogenesis. Female KK-A y obese mice (n=10) were injected subcutaneously with GH (3.5 mg/kg/day) for 30 days from 42 days old. As a control, physiological saline was administered (n=10). At the terminal point (71 days old), GH administration affected linear growth, and the Lee obesity index (3 square root body weight/nasoanal length 1000) was significantly decreased. Rates of inguinal and perimetric white adipose pads per body weight also decreased. Free fatty acid levels decreased, while plasma insulin concentrations and homeostasis model assessment insulin resistance were increased (P<0.01). Plasma insulin-like growth factor � (IGF-1) levels markedly rose (P<0.00001). Uncoupling protein1 (UCP1) and UCP3 mRNA expressions in brown adipose tissue were inhibited (P<0.05). Continuous GH therapy changed obese body composition toward lean, however, the consequence could be the negative regulation of thermogenesis.","PeriodicalId":88751,"journal":{"name":"The open endocrinology journal","volume":"4 1","pages":"3-8"},"PeriodicalIF":0.0,"publicationDate":"2010-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68057233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Lemoinne, J. Baudel, A. Galbois, G. Offenstadt, É. Maury
{"title":"Sudden Respiratory Failure in a Patient with Cushing`s Syndrome","authors":"S. Lemoinne, J. Baudel, A. Galbois, G. Offenstadt, É. Maury","doi":"10.2174/1874216501004010001","DOIUrl":"https://doi.org/10.2174/1874216501004010001","url":null,"abstract":"A 79 year-old patient with prostate cancer related Cushing's syndrome was referred to ICU for acute respiratory distress occurring two days after introduction of mifepristone. Pneumocystis jirovecii pneumonia was diagnosed. Despite anti pneumocystis therapy and supportive treatment, the patient died of multiple organ failure. The relationship between mifepristone and Cushing's syndrome and potential implications are discussed. Cushing's syndrome is a classical but rare disease resulting from exposure to excessive concentrations of glucocorticoid. When surgery is not feasible medical therapy should be discussed. A 79 year-old man was admitted to intensive care unit for acute respiratory distress. He had been treated for prostate cancer for 12 years, with radiotherapy and hormonotherapy. The last prostate-specific antigen (PSA) level was (0, 24 ng/ml) while pelvis MRI disclosed irregular prostate consistent with radiotherapy after-effects without any sign of recurrence of malignancy. He was referred 3 months before to the general ward because of depression, severe systemic hypertension, hypokalaemia and diabetes mellitus. Endogenous hypercortisolism was diagnosed. Static and dynamic analysis: (plasma cortisol level at 8 am : 1564 nmol/l (normal<200 nmol/l), 24h urinary free cortisol excretion: 20200 nmol/24h (normal <270 nmol/24h), no suppression of plasma cortisol with low dose of dexamethasone, adrenocorticotropic hormone (ACTH) : 145 ng/l.(normal<50 ng/l)) were in favour of an ACTH dependent Cushing's syndrome. Considering normal pituitary MRI, final diagnosis was paraneoplastic Cushing's syndrome. CT scan imaging of the thorax (Fig. 1), abdomen and pelvis disclosed bilateral adrenal hyperplasia but did not show any thoracic or pancreatic tumours which are the most common tumours responsible for ectopic ACTH secretion.","PeriodicalId":88751,"journal":{"name":"The open endocrinology journal","volume":"4 1","pages":"1-2"},"PeriodicalIF":0.0,"publicationDate":"2010-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68056210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ni Zeng, Jennifer-Ann Bayan, Lina He, Bangyan Stiles
{"title":"The Role of PTEN in β-Cell Growth.","authors":"Ni Zeng, Jennifer-Ann Bayan, Lina He, Bangyan Stiles","doi":"10.2174/1874216501004010023","DOIUrl":"https://doi.org/10.2174/1874216501004010023","url":null,"abstract":"<p><p>This paper describes the biological functions of PTEN and the PTEN regulated signaling pathway in pancreatic β-cells. PTEN has been shown to regulate the regeneration of β-cells. We review the pathways that are controlled by PTEN signaling and their functions in β-cell regeneration. In particular, we describe the unique effect of <i>Pten</i> deletion in β-cells. Unlike its effect in other tissues, <i>Pten</i> deletion does not lead to tumor formation but does enhance β-cell proliferation and function. In addition to the literature review, we also report new results exploring PTEN loss in adult β-cells. We demonstrate that inducing PTEN loss in adult cells has the same regenerative effects previously found for prenatal deletion.</p>","PeriodicalId":88751,"journal":{"name":"The open endocrinology journal","volume":"4 ","pages":"23-32"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3708799/pdf/nihms-419651.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31579873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nidhi Rohatgi, Maria S Remedi, Guim Kwon, Kirk L Pappan, Connie A Marshall, Michael L McDaniel
{"title":"Therapeutic Strategies to Increase Human β-Cell Growth and Proliferation by Regulating mTOR and GSK-3/β-Catenin Pathways.","authors":"Nidhi Rohatgi, Maria S Remedi, Guim Kwon, Kirk L Pappan, Connie A Marshall, Michael L McDaniel","doi":"10.2174/1874216501004010040","DOIUrl":"https://doi.org/10.2174/1874216501004010040","url":null,"abstract":"<p><p>This perspective delineates approaches to develop therapeutic strategies to stimulate the proliferative potential of adult human β-cells in vitro. Previous findings demonstrated that nutrients, through regulation of mTOR signaling, promote regenerative processes including DNA synthesis, cell cycle progression and β-cell proliferation in rodent islets but rarely in human islets. Recently, we discovered that regulation of the Wnt/GSK-3/β-catenin pathway by directly inhibiting GSK-3 with pharmacologic agents, in combination with nutrient activation of mTOR, was required to increase growth and proliferation in human islets. Studies also revealed that nuclear translocation of β-catenin in response to GSK-3 inhibition regulated these processes and was rapamycin sensitive, indicating a role for mTOR. Human islets displayed a high level of insulin resistance consistent with the inability of exogenous insulin to activate Akt and engage the Wnt pathway by GSK-3 inhibition. This insulin resistance in human islets is not present in rodent islets and may explain the differential requirement in human islets to inhibit GSK-3 to enhance these regenerative processes. Human islets exhibited normal insulin secretion but a loss of insulin content, which was independent of all treatment conditions. The loss of insulin content may be related to insulin resistance, the isolation process or culture conditions. In this perspective, we provide strategies to enhance the proliferative capacity of adult human β-cells and highlight important differences between human and rodent islets: the lack of a nutrient response, requirement for direct GSK-3 inhibition, insulin resistance and loss of insulin content that emphasize the physiological significance of conducting studies in human islets.</p>","PeriodicalId":88751,"journal":{"name":"The open endocrinology journal","volume":"4 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3856862/pdf/nihms493240.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31956172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M L Golson, A Ackermann Misfeldt, U G Kopsombut, C P Petersen, M Gannon
{"title":"High Fat Diet Regulation of β-Cell Proliferation and β-Cell Mass.","authors":"M L Golson, A Ackermann Misfeldt, U G Kopsombut, C P Petersen, M Gannon","doi":"10.2174/1874216501004010066","DOIUrl":"10.2174/1874216501004010066","url":null,"abstract":"<p><p>Type 2 Diabetes (T2D) is characterized by relative insulin insufficiency, caused when peripheral tissues such as liver, muscle, and adipocytes have a decreased response to insulin. One factor that elevates the risk for insulin resistance and T2D is obesity. In obese patients without T2D and initially in people who develop T2D, pancreatic β-cells are able to compensate for insulin resistance by increasing β-cell mass, effected by increased proliferation and hypertrophy, as well as increased insulin secretion per β-cell. In patients that go on to develop T2D, however, this initial period of compensation is followed by β-cell failure due to decreased proliferation and increased apoptosis. The forkhead box transcription factor FoxM1 is required for β-cell replication in mice after four weeks of age, during pregnancy, and after partial pancreatectomy. We investigated whether it is also required for β-cell proliferation due to diet-induced obesity.</p>","PeriodicalId":88751,"journal":{"name":"The open endocrinology journal","volume":"4 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3856766/pdf/nihms492411.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31956171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bromocriptine Response in Pathological Hyperprolactinemia: A 34 Year Follow-Up of a Homogeneous Population of 827 Patients","authors":"B. Corenblum","doi":"10.2174/1874216500903010038","DOIUrl":"https://doi.org/10.2174/1874216500903010038","url":null,"abstract":"patients with symptomatic pathological hyperprolactinemia were treated with bromocriptine. The evaluation, treatment, and follow-up was by a single individual, making this a large and unique homogeneous group for purposes of treatment evaluation.","PeriodicalId":88751,"journal":{"name":"The open endocrinology journal","volume":"3 1","pages":"38-41"},"PeriodicalIF":0.0,"publicationDate":"2009-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68056167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
O. Poyrazoglu, Y. Ozkan, M. Ozden, R. Çolak, G. Özalp, E. Dönder
{"title":"L-Thyroxine Treatment of Patients with Subclinical HypothyroidismReduce Inflammation","authors":"O. Poyrazoglu, Y. Ozkan, M. Ozden, R. Çolak, G. Özalp, E. Dönder","doi":"10.2174/1874216500903010034","DOIUrl":"https://doi.org/10.2174/1874216500903010034","url":null,"abstract":"Background: Subclinical hypothyroidism (SCH) has been found to be associated with cardiovascular disease including atherosclerosis which is also called inflammatory disorder. The objective of this study was, to investigate the efficacy of L-thyroxine therapy on inflammation in patients with SCH and to determine whether treatment of SCH would reduce inflammation. Methods: Twenty patients with thyroid stimulating hormone levels between 5 and 10 mU/L and twenty healthy persons (control) were enrolled to the study. 0.025-0.075 mg/d L-thyroxine therapy was given to the patients. Patients were followed till they became euthyroid. C-reactive protein (CRP), lipid profile and thyroid function tests were evaluated. CRP was determined by a high sensitivity immunoassay. Results: CRP, total cholesterol and low-density lipoprotein (LDL) were significantly elevated in patients with subclinical hypothyroidism compared to the control group at baseline (p<0.01, p<0.05, p<0.001, respectively). L-thyroxine therapy significantly decreased CRP (p<0.01) and low-density lipoprotein in treatment group (p<0.05). Nevertheless, no significant change was found in other lipid parameters. Conclusion: These findings demonstrate that patients with SCH are characterized by inflammatory disorders and higher lipid profile.","PeriodicalId":88751,"journal":{"name":"The open endocrinology journal","volume":"3 1","pages":"34-37"},"PeriodicalIF":0.0,"publicationDate":"2009-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68056154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of Statins on Insulin-Like Growth Factor-1 Gene Expression in Fructose Induced Metabolic Syndrome in Rats","authors":"O. Shaker, Doaa A. Sourour, Mohamed Taha","doi":"10.2174/1874216500903010028","DOIUrl":"https://doi.org/10.2174/1874216500903010028","url":null,"abstract":"Background and Purpose: Insulin-like growth factor-1 (IGF-1) was found to have a role in both glucose homeostasis and cardiovascular disease. The present study was designed to compare the effects of fluvastatin and metformin on IGF-1 mRNA expression within the liver and on other individual components of the metabolic syndrome induced in rats by high fructose feeding. Experimental Approach: Rats fed 60% fructose in diet for 6 weeks were treated daily with fluvastatin (3.75mg/kg/day) or metformin (200mg/kg/day) during the last 2 weeks and compared with untreated fructose fed group. Fasting levels of plasma cholesterol, triglyceride, glucose, insulin, nitric oxide products, IGF-1 and IGF-1 mRNA within the liver as well as systolic blood pressure and body weight were determined. Results: Compared to control rats, the fructose fed group developed hypertension, hyperlipidemia, hyperinsulinemia, hyperglycemia and endothelial dysfunction as well as decreased levels of plasma IGF-1 and its mRNA within the liver. Fructose fed rats treated with fluvastatin or metformin for 2 weeks showed significant decrease in plasma cholesterol, triglyceride, insulin and glucose levels compared to untreated fructose fed group. Also, both drugs increased significantly plasma levels of nitric oxide products and IGF-1 together with significant increase in IGF-1 mRNA within the liver. However, only metformin treated rats showed significant decrease in systolic blood pressure compared to fructose fed group. Conclusions: This study showed that in a rat model of insulin resistance, fluvastatin improves the metabolic profile and increases plasma level of IGF-1 and its gene expression as effective as metformin.","PeriodicalId":88751,"journal":{"name":"The open endocrinology journal","volume":"3 1","pages":"28-33"},"PeriodicalIF":0.0,"publicationDate":"2009-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68056138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Carboxyl-Terminal Parathyroid Hormone Receptor Regulates Osteocyte Cytoskeleton Through Mechanisms Dependent Upon Calcium Influx","authors":"A. A. Selim, J. Potts, F. Bringhurst, P. Divieti","doi":"10.2174/1874216500903010022","DOIUrl":"https://doi.org/10.2174/1874216500903010022","url":null,"abstract":"Parathyroid hormone (PTH) exerts classical actions on bone and mineral metabolism by activating PTH/PTHrP receptors (PTH1Rs) on target cells, including osteoblasts and osteocytes in bone. Such bone cells also express an addi- tional receptor for PTH distinct from PTH1Rs, that recognize determinants within the carboxyl (C)-terminal portion of PTH (1-84), the C-terminal PTH receptor (\"CPTHR\"). CPTHRs previously were found to regulate intercellular communi- cation, cell survival and to increase cytosolic calcium in bone cells in a manner dependent upon voltage-sensitive calcium channels. As intracellular free calcium is known to regulate cytoskeletal function, we sought to determine if CPTHR acti- vation altered cytoskeletal structure in OC-59 osteocytic cells, which lack PTH1Rs but express abundant CPTHRs. Treatment of OC-59 cells with 100 nM hPTH (53-84) for 10 minutes induced marked condensations of the cytoskeletal components actin and vinculin, as visualized by immunofluorescence in permeabilized cells. This effect was not observed in cells treated with vehicle alone or with the CPTHR ligand for only 2 minutes. These changes also were not seen in cells exposed for 10 minutes to the inactive CPTH analog, (Ala 55-57 )PTH (53-84), which does not bind to CPTHRs and does not induce a calcium signal in OC-59 cells. Cytoskeletal condensation induced by hPTH (53-84) was blocked by pre- treatment with gadolinium chloride, which is known to inhibit CPTHR-dependent calcium responses in these cells. Taken together, these results suggest that calcium influx induced by CPTHR activation may play an important role in regulating the cytoskeleton in osteocytes.","PeriodicalId":88751,"journal":{"name":"The open endocrinology journal","volume":"3 1","pages":"22-27"},"PeriodicalIF":0.0,"publicationDate":"2009-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68056088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}