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Glutamine or Glutamine Dipeptide Supplementation Improves Gluconeogenesis and Liver Glycogenosis in Type 1 Diabetic Rats

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Journal of Pharmacy and Pharmacology 2019年第7期7卷 398-407页

作者： Silvia Carla S.F.Azevedo Carlos Vinicius D.da Rosa Ana Luiza M.Wunderlich Laís A.Yamada Isabela R.Mariano Camila Bataglini Nayra T.D.Branquinho Scarlett R.Raposo Roberto B.Bazotte Edmara A.Baroni Maria Raquel M.Natali Maria Montserrat D.Pedrosa Vilma A.F.de Godoi Program of Graduate Studies in Cell and Molecular Biology State University of MaringáMaringá87020-900Brazil Program of Graduate Studies in Physiological Sciences State University of MaringáMaringá87020-900Brazil Undergraduation in Biological Sciences University Center of MaringáMaringá87050-390Brazil Department of Pharmacology and Therapeutics State University of MaringáMaringá87020-900Brazil Department of Physiological Sciences State University of MaringáMaringá87020-900Brazil Department of Morphological Sciences State University of MaringáMaringá87020-900Brazil

The effects of the supplementation with L-glutamine(GLN)or L-alanyl-L-glutamine(GDP)on the progression of the systemic and hepatic metabolic status of rats having untreated type 1 diabetes mellitus(T1DM)were *** Wistar diabetic rats(streptozotocin,60 mg/kg)were allotted to four groups supplemented by gavage for thirty days as follows:control and diabetic receiving saline;diabetic receiving GLN(248 mg/kg);and diabetic receiving GDP(400 mg/kg).Body weight,plasmatic parameters and kidney function were *** hepatocytes were used to assess gluconeogenic *** and kidney were used for morphological analyses.T1DM decreased the number and increased the area of the hepatocytes,possibly because of the observed enlargement of glycogen *** weight,glomerular area and proteinuria increased,and glomerular filtration rate decreased,in non-supplemented T1DM *** area and proteinuria were reversed by both *** T1DM hepatocytes released less glucose,which could have been diverted to glycogen synthesis and secondary glycogenosis observed in T1DM;this was partially reversed by the *** results point to a possible beneficial effect of glutamine on the metabolic and hepatic impairments of T1DM.

关键词： Type 1 diabetes mellitus L-glutamine glutamine dipeptide gluconeogenesis glycogenosis

Skeletal muscle as a therapeutic target for delaying type 1 diabetic complications

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World Journal of Diabetes 2015年第17期6卷 1323-1336页

作者： Samantha K Coleman Irena A Rebalka Donna M D'Souza Thomas J Hawke Department of Pathology and Molecular Medicine McMaster University

Type 1 diabetes mellitus(T1DM) is a chronic autoimmune disease targeting the pancreatic beta-cells and rendering the person hypoinsulinemic and hyperglycemic. Despite exogenous insulin therapy, individuals with T1 DM will invariably develop long-term complications such as blindness, kidney failure and cardiovascular disease. Though often overlooked, skeletal muscle isalso adversely affected in T1 DM, with both physical and metabolic derangements reported. As the largest metabolic organ in the body, impairments to skeletal muscle health in T1 DM would impact insulin sensitivity, glucose/lipid disposal and basal metabolic rate and thus affect the ability of persons with T1 DM to manage their disease. In this review, we discuss the impact of T1 DM on skeletal muscle health with a particular focus on the proposed mechanisms involved. We then identify and discuss established and potential adjuvant therapies which, in association with insulin therapy, would improve the health of skeletal muscle in those with T1 DM and thereby improve disease managementultimately delaying the onset and severity of other longterm diabetic complications.

关键词： Type 1 diabetes mellitus Skeletal muscle Exercise

Vascular dysfunction in diabetes: The endothelial progenitor cells as new therapeutic strategy

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World Journal of Diabetes 2011年第6期2卷 92-97页

作者： Adriana Georgescu Petru Poni' Institute of Macromolecular Chemistry Institute of Cellular Biology and Pathology 'Nicolae Simionescu' of Romanian Academy

The vascular endothelium is a critical determinant of dia- betes-associated vascular complications, and improving endothelial function is an important target for therapy. Diabetes mellitus contributes to endothelial cell injury and dysfunction. Endothelial progenitor cells (EPCs) play a critical role in maintaining endothelial function and might affect the progression of vascular disease. EPCs are essential to blood vessel formation, can differentiate into mature endothelial cells, and promote the repair of damaged endothelium. In diabetes, the circulating EPC count is low and their functionality is impaired. The me- chanisms that underlie this reduced count and impaired functionality are poorly understood. Knowledge of the status of EPCs is critical for assessing the health of the vascular system, and interventions that increase the number of EPCs and restore their angiogenic activity in diabetes may prove to be particularly beneficial. The pre-sent review outlines current thinking on EPCs' therapeutic potential in endothelial dysfunction in diabetes, as well as evidence-based perspectives regarding their use for vascular regenerative medicine.

关键词： Diabetes mellitus Vascular dysfunction Endothelial progenitor cells

Peroxisome proliferator-activated receptors for hypertension

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World Journal of Cardiology 2014年第8期6卷 744-754页

作者： Daisuke Usuda Tsugiyasu Kanda Department of Community Medicine Kanazawa Medical University Himi Municipal HospitalHimi-shi 935-8531Toyama-kenJapan

Peroxisome proliferator-activated receptors(PPARs) are ligand-activated transcription factors belonging to the nuclear receptor superfamily, which is composed of four members encoded by distinct genes(α, β, γ, and δ). The genes undergo transactivation or transrepression under specific mechanisms that lead to the induction or repression of target gene expression. As is the case with other nuclear receptors, all four PPAR isoforms contain five or six structural regions in four functional domains; namely, A/B, C, D, and E/F. PPARs have many functions, particularly functions involving control of vascular tone, inflammation, and energy homeostasis, and are, therefore, important targets for hypertension, obesity, obesity-induced inflammation, and metabolic syndrome in general. Hence, PPARs also represent drug targets, and PPARα and PPARγ agonists are used clinically in the treatment of dyslipidemia and type 2 diabetes mellitus, respectively. Because of their pleiotropic effects, they have been identified as active in a number of diseases and are targets for the development of a broad range of therapies for a variety of diseases. It is likely that the range of PPARγ agonist therapeutic actions will result in novel approaches to lifestyle and other diseases. The combination of PPARs with reagents or with other cardiovascular drugs, such as diuretics and angiotensin Ⅱ receptor blockers, should be *** article provides a review of PPAR isoform characteristics, a discussion of progress in our understanding of the biological actions of PPARs, and a summary of PPAR agonist development for patient management. We also include a summary of the experimental and clinical evidence obtained from animal studies and clinical trials conducted to evaluate the usefulness and effectiveness of PPAR agonists in the treatment of lifestyle-related diseases.

关键词： Peroxisome proliferator-activated receptors Nuclear receptor Isoform mRNA Blood pressure Hypertension Obesity Angiotensin Ⅱ receptor blocker Diabetes mellitus

Atypical presentation of acute and chronic coronary artery disease in diabetics

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World Journal of Cardiology 2014年第8期6卷 802-813页

作者： Hadi AR Hadi Khafaji Jassim M Al Suwaidi Internal Medicine Department Toronto General HospitalToronto UniversityTorontoOntario M5G 2C4Canada Qatar Cardiovascular Research Center and Heart Hospital Hamad Medical Corporation DohaQatar

In patients with diabetes mellitus, cardiovascular disease is the principal cause of mortality and chest pain is the most frequent symptom in patients with stable and acute coronary artery disease. However, there is little knowledge concerning the pervasiveness of uncommon presentations in diabetics. The symptomatology of acute coronary syndrome, which comprises both pain and non-pain symptoms, may be affected by traditional risk factors such as age, gender, smoking, hypertension, diabetes, and dyslipidemia. Such atypical symptoms may range from silent myocardial ischemia to a wide spectrum of non-chest pain symptoms. Worldwide, few studies have highlighted this under-investigated subject, and this aspect of ischemic heart disease has also been under-evaluated in the major clinical trials. The results of these studies are highly diverse which makes definitive conclusions regarding the spectrum of atypical presentation of acute and even stable chronic coronay artery disease difficult to confirm. This may have a significant impact on the morbidity and mortality of coronary artery disease in diabetics. In this up-to-date review we will try to analyze the most recent studies on the atypical presentations in both acute and chronic ischemic heart disease which may give some emphasis to this under-investigated topic.

关键词： Diabetes mellitus Acute coronary syndrome Acute myocardial infarction Ischemic heart disease Atypical presentation Silent myocardial ischemia

Enterovirus and type 1 diabetes: What is the matter?

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World Journal of Diabetes 2015年第6期6卷 828-839页

作者： Carla Sanchez Bergamin Sergio Atala Dib Department of Medicine S?o Paulo Federal University

A complex interaction of genetic and environmental factors can trigger the immune-mediated mechanism responsible for type 1 diabetes mellitus(T1DM) establishment. Environmental factors may initiate and possibly sustain, accelerate, or retard damage to β-cells. The role of environmental factors in this process has been exhaustive studied and viruses are among the most probable ones, especially enteroviruses. Improvements in enterovirus detection methods and randomized studies with patient follow-up have confirmed the importance of human enterovirus in the pathogenesis of T1 DM. The genetic risk of T1 DM and particular innate and acquired immune responses to enterovirus infection contribute to a tolerance to T1DM-related autoantigens. However, the frequency, mechanisms, and pathways of virally induced autoimmunity and β-cell destruction in T1 DM remain to be determined. It is difficult to investigate the role of enterovirus infection in T1 DM because of several concomitant mechanisms by which the virus damages pancreatic β-cells, which, consequently, may lead to T1 DM establishment. Advances in molecular and genomic studies may facilitate the identification of pathways at earlier stages of autoimmunity when preventive and therapeutic approaches may be more effective.

关键词： Virus Enterovirus Coxsackievirus Type 1diabetes mellitus Auto-immune diabetes Pathogenesis

Insulin producing cells established using non-integrated lentiviral vector harboring PDX1 gene

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World Journal of Stem Cells 2013年第4期5卷 217-228页

作者： Zahra Niki Boroujeni Ahmad Aleyasin Department of Medical Biotechnology National Institute of Genetic Engineering and Biotechnology

AIM: To investigate reprogramming of human adipose tissue derived stem cells into insulin producing cells using non-integrated lentivirus harboring PDX1 ***: In this study, human adipose tissue derived stem cells(hADSCs) were obtained from abdominal adipose tissues by liposuction, selected by plastic adhesion, and characterized by flow cytometric *** ADSCs were differentiated into adipocytes and osteocytes using differentiating medium to confirm their multipotency. Non-integrated lentiviruses harboring PDX1(Non-integrated LV-PDX1) were constructed using specific plasmids(pLV-HELP, pMD2G, LV-105-PDX1-1).Then, hADSCs were transduced with non-integrated LVPDX1. After transduction, ADSCsPDX1+were cultured in high glucose DMEM medium supplement by B27, nicotinamide and βFGF for 21 d. Expressions of PDX1 andinsulin were detected at protein level by immunofluorescence analysis. Expressions of PDX1, neurogenin3(Ngn3), glucagon, glucose transporter2(Glut2) and somatostatin as specific marker genes were investigated at mRNA level by quantitative RT-PCR. Insulin secretion of hADSCsPDX1+in the high-glucose medium was detected by electrochemiluminescence test. Human ADSCsPDX1+were implanted into hyperglycemic ***: Human ADSCs exhibited their fibroblast-like morphology and made colonies after 7-10 d of *** of hADSCs identified by FACS analysis showed that hADSCs were positive for mesenchymal cell markers and negative for hematopoietic cell markers that guaranteed the lack of hematopoietic contamination. In vitro differentiation of hADSCs into osteocytes and adipocytes were detected by Alizarin red and Oil red O staining and confirmed their multilineage differentiation ability. Transduced hADSCs+PDX1became round and clusters in the differentiation medium. The appropriate expression of PDX1 and insulin proteins was confirmed using immunocytochemistry *** expressions of PDX1, Ngn3, glucagon, Glut2and somatostatin were d

关键词： Diabetes mellitus Human adipose tissue derived stem cells Non-integrated lentiviruses PDX1 Insulin producing cells