Combined therapy with metformin and insulin attenuates systemic and hepatic alterations in a model of high-fat diet-/streptozotocin-induced diabetes.

Abstract:

:In this study we have explored the pathogenesis of the hepatic alterations which occur in diabetes and the modulation of these complications by the combination of metformin adjunct treatment and insulin monotherapy. For this purpose, diabetic rats were treated with insulin (DM + Ins) or metformin plus insulin (DM + Met + Ins). Biochemical and cardiometabolic parameters were analysed by spectrophotometry. Intravital microscopy was used to study the hepatic microcirculation. In the liver tissue, real-time PCR was used to analyse oxidative stress enzymes, inflammatory markers and receptors for advanced glycation end products (AGE) (RAGE) gene expression. Lipid peroxidation was assessed by thiobarbituric acid reactive species (TBARs) analyses. AGE deposition and RAGE protein expression were studied by fluorescence spectrophotometry and Western blot respectively. Body weight, %HbA1c , urea, total proteins and oxidative stress parameters were found to be similarly improved by insulin or Met + Ins treatments. On the other hand, Met + Ins treatment showed a more pronounced effect on fasting blood glucose level than insulin monotherapy. Fructosamine, uric acid, creatinine, albumin and amylase levels and daily insulin dose requirements were found to be only improved by the combined Met + Ins treatment. Liver, renal and pancreatic dysfunction markers were found to be more positively affected by metformin adjunct therapy when compared to insulin treatment. Liver microcirculation damage was found to be completely protected by Met + Ins treatment, while insulin monotherapy showed no effect. Our results suggest that oxidative stress, microcirculatory damage and glycated proteins could be involved in the aetiology of liver disease due to diabetes. Additionally, metformin adjunct treatment improved systemic and liver injury in induced diabetes and showed a more pronounced effect than insulin monotherapy.

journal_name

Int J Exp Pathol

authors

Silvares RR,Pereira EN,Flores EE,Estato V,Reis PA,Silva IJ,Machado MP,Neto HC,Tibiriça E,Daliry A

doi

10.1111/iep.12184

subject

Has Abstract

pub_date

2016-06-01 00:00:00

pages

266-77

issue

3

eissn

0959-9673

issn

1365-2613

journal_volume

97

pub_type

杂志文章
  • In the absence of Epstein-Barr virus infection, phorbol ester modulates apoptosis in cycloheximide-treated Burkitt's lymphoma (BJA-B) cells.

    abstract::We have shown previously that cycloheximide (CHX), a potent protein synthesis inhibitor, induces high levels of apoptosis in Epstein-Barr virus free (EBV(-)) Burkitt's lymphoma (BJA-B) cells, with comparably reduced levels of apoptosis in the EBV positive (EBV(+)) cells. Modulation of CHX-induced apoptosis in EBV(-) a...

    journal_title:International journal of experimental pathology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2613.1997.170350.x

    authors: Ishii H,Tamauchi H,Gobe GC

    更新日期:1997-06-01 00:00:00

  • Pathobiological properties of the ubiquitin ligase Nedd4L in melanoma.

    abstract::A recent global gene expression profiling study unexpectedly showed that activated oncogenic NRAS may recruit neural precursor cell expressed, developmentally downregulated 4L (Nedd4L; a human homologue of Nedd4-2) in cultured melanoma cells. However, whether Nedd4L was expressed in melanoma tissues or participated in...

    journal_title:International journal of experimental pathology

    pub_type: 杂志文章

    doi:10.1111/iep.12051

    authors: Kito Y,Bai J,Goto N,Okubo H,Adachi Y,Nagayama T,Takeuchi T

    更新日期:2014-02-01 00:00:00

  • A new fibroblast growth stimulating activity from the human megakaryoblastic leukaemia cell line ELF-153: in vitro and in vivo findings.

    abstract::Although the exact mechanism for the progression of myelofibrosis in acute megakaryoblastic leukaemia is unclear, certain humoral factors released from the proliferating megakaryoblasts that are unable to store these factors in their defective alpha-granules, including platelet derived growth factor (PDGF), fibroblast...

    journal_title:International journal of experimental pathology

    pub_type: 杂志文章

    doi:

    authors: Hassan HT,Hanauske AR,Lux E,Kleine HD,Freund M

    更新日期:1995-10-01 00:00:00

  • Cell proliferation and apoptosis in isoprenaline-induced sialosis in the rat submandibular glands.

    abstract::Regression of submandibular acinar cell hyperplasia after withdrawal of the mitogenic stimulus induced by isoprenaline was studied in male Wistar rats. Intraperitoneal administration of 39 mg of isoprenaline, in divided doses over a 9-day period, resulted in a marked increase in gland size and weight. The proportional...

    journal_title:International journal of experimental pathology

    pub_type: 杂志文章

    doi:

    authors: Chisholm DM,Adi MM

    更新日期:1995-08-01 00:00:00

  • Snake coiled fibres in rat soleus muscle in chloroquine induced myopathy share immunohistochemical characteristics with amyloid depositions in Alzheimer's disease brain tissue.

    abstract::Pathological and immunopathological studies were carried out on snake coiled fibres (SCF) which occurred in affected soleus muscle in chloroquine treated rats. The SCF began to appear in denervated soleus muscle by 8 days after chloroquine injection. By day 14, typical SCF were observed with an unusual swirling patter...

    journal_title:International journal of experimental pathology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2613.1997.9950333.x

    authors: Tsuzuki K,Fukatsu R,Takamaru Y,Yoshida T,Hayashi Y,Kobayashi K,Fujii N,Takahata N

    更新日期:1997-02-01 00:00:00

  • Induction and treatment of anergy in murine leprosy.

    abstract::Leprosy is a disease consisting of a spectrum of clinical, bacteriological, histopathological and immunological manifestations. Tuberculoid leprosy is frequently recognized as the benign polar form of the disease, while lepromatous leprosy is regarded as the malignant form. The different forms of leprosy depend on the...

    journal_title:International journal of experimental pathology

    pub_type: 杂志文章

    doi:10.1111/iep.12108

    authors: Juarez-Ortega M,Hernandez VG,Arce-Paredes P,Villanueva EB,Aguilar-Santelises M,Rojas-Espinosa O

    更新日期:2015-02-01 00:00:00

  • Characterization of the dengue virus-induced helper cytokine.

    abstract::Dengue type 2 virus (DV) induces a subpopulation of T lymphocytes of mouse spleen to secrete a soluble helper cytokine (HF) which enhances the DV-specific IgM antibody plaque forming cells (PFC). The present study undertaken to purify and characterize HF shows that it can be purified by low pressure liquid chromatogra...

    journal_title:International journal of experimental pathology

    pub_type: 杂志文章

    doi:

    authors: Chaturvedi P,Mukherjee R,Chaturvedi UC,Mathur A

    更新日期:1992-06-01 00:00:00

  • The acute phase protein haptoglobin is locally expressed in arthritic and oncological tissues.

    abstract::Haptoglobin is an acute phase protein known to be highly expressed in the liver. Recently, we showed increased local arterial haptoglobin expression after flow-induced arterial remodelling and found that haptoglobin is involved in cell migration and arterial restructuring probably through accumulation of a temporary g...

    journal_title:International journal of experimental pathology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2613.2003.00336.x

    authors: Smeets MB,Fontijn J,Kavelaars A,Pasterkamp G,De Kleijn DP

    更新日期:2003-04-01 00:00:00

  • Factors influencing the ability of different mycoplasmas to colonize the genital tract of hormone-treated female mice.

    abstract::Colonization of the genital tract of female mice, mainly BALB/c, by Mycoplasma genitalium, M. pneumoniae and M. pulmonis was enhanced by pretreatment of the mice with progesterone. M. fermentans, M. hominis and M. salivarium, and three serotypes and two untyped strains of Ureaplasma urealyticum colonized under the inf...

    journal_title:International journal of experimental pathology

    pub_type: 杂志文章

    doi:

    authors: Furr PM,Taylor-Robinson D

    更新日期:1993-02-01 00:00:00

  • Long non-coding RNA GAS5 overexpression inhibits M2-like polarization of tumour-associated macrophages in SMCC-7721 cells by promoting PTEN expression.

    abstract::Tumour-associated macrophage (TAM) polarization is associated with hepatocellular carcinoma but the molecular mechanism of this polarization is still unknown. Peripheral blood mononuclear cells were induced to differentiate into M0, M1 and M2 macrophages and TAMs. TAMs were transfected with pcDNA3.1-GAS5, pcDNA3.1-NC,...

    journal_title:International journal of experimental pathology

    pub_type: 杂志文章

    doi:10.1111/iep.12374

    authors: Wang X,Li FY,Zhao W,Gao ZK,Shen B,Xu H,Cui YF

    更新日期:2020-12-01 00:00:00

  • Relationship of impairment induced by intracellular S-adenosylhomocysteine accumulation with DNA methylation in human umbilical vein endothelial cells treated with 3-deazaadenosine.

    abstract::The aim of this study was to estimate the relationship of endothelial dysfunction induced by intracellular S-adenosylhomocysteine (SAH) accumulation and DNA methylation in human umbilical vein endothelial cells (HUVEC). The isolated HUVEC were incubated with 3-deazaadenosine (DZA) to induce experimental intracellular ...

    journal_title:International journal of experimental pathology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2613.2009.00687.x

    authors: Yu X,Ling W,Mi M

    更新日期:2009-12-01 00:00:00

  • Production of salivary microlithiasis in cats by parasympathectomy: light and electron microscopy.

    abstract::Salivary glands of cat were examined from 1 to 42 days following parasympathectomy and compared with contralateral normal control glands. Microliths were detected by light microscopy in none of 11 parotid, 31 out of 41 submandibular and four out of 22 sublingual glands following parasympathectomy, and one out of 19 pa...

    journal_title:International journal of experimental pathology

    pub_type: 杂志文章

    doi:

    authors: Triantafyllou A,Harrison JD,Garrett JR

    更新日期:1993-02-01 00:00:00

  • Characterization of the murine model of schistosomal hepatic periportal fibrosis ('pipestem' fibrosis).

    abstract::During mild (one to two pairs of worms) and prolonged (23 weeks or more) mouse infections with Schistosoma mansoni, but not with S. japonicum, periovular granulomas and fibrosis were seen to be preferentially located along periportal tissues. This caused fibrotic expansion of the portal spaces on a background of norma...

    journal_title:International journal of experimental pathology

    pub_type: 杂志文章

    doi:

    authors: Andrade ZA,Cheever AW

    更新日期:1993-04-01 00:00:00

  • Serum and tissue level of insulin-like growth factor-I (IGF-I) and IGF-I binding proteins as an index of pancreatitis and pancreatic cancer.

    abstract::Previously we have found deregulation of collagen metabolism in human pancreatitis and pancreatic cancer tissues. Insulin-like growth factor-I (IGF-I) is known to stimulate collagen biosynthesis through interaction with IGF-I receptor. IGF-I binding proteins (BPs) regulate the activity of IGF-I. We investigated whethe...

    journal_title:International journal of experimental pathology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2613.2002.00237.x

    authors: Karna E,Surazynski A,Orłowski K,Łaszkiewicz J,Puchalski Z,Nawrat P,Pałka J

    更新日期:2002-10-01 00:00:00

  • Different effect of cyclosporin A on arthritides induced by a muramyl dipeptide analogue or the complete adjuvant in rats.

    abstract::Muramyl dipeptide-Lys(L18) given by daily subcutaneous injection for 14 days induced arthritis in male Lewis, Fischer and nude rats, to a lesser degree in the last two than in the first strain. On the other hand, a single intradermal administration of Freund's complete adjuvant induced arthritis in Lewis and Fischer b...

    journal_title:International journal of experimental pathology

    pub_type: 杂志文章

    doi:

    authors: Sugawara T,Takada S,Furuhama K,Takayama S,Nomura M,Kato M

    更新日期:1995-06-01 00:00:00

  • A central role for the mast cell in early phase vasculitis in the Brown Norway rat model of vasculitis: a histological study.

    abstract::Administration of mercuric chloride (HgCl(2)) to Brown Norway rats causes Th2-dominated autoimmunity with raised immunoglobulin E concentrations and gut vasculitis, both of which are T-cell dependent, peak at 14 days after starting HgCl(2) and then spontaneously resolve. If animals are re-challenged with HgCl(2) 6 wee...

    journal_title:International journal of experimental pathology

    pub_type: 杂志文章

    doi:10.1111/j.0959-9673.2004.00382.x

    authors: Vinen CS,Turner DR,Oliveira DB

    更新日期:2004-06-01 00:00:00

  • Erythropoietin is involved in angiogenesis in human primary melanoma.

    abstract::In this study, the extent of angiogenesis, evaluated as microvascular volume density, immunoreactivity of tumour cells to erythropoietin (Epo) and of endothelial cells to Epo receptor (EpoR) have been correlated in human primary melanoma specimens. Results showed that Epo/EpoR expression correlate with angiogenesis an...

    journal_title:International journal of experimental pathology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2613.2010.00731.x

    authors: Ribatti D,Nico B,Perra MT,Longo V,Maxia C,Annese T,Piras F,Murtas D,Sirigu P

    更新日期:2010-12-01 00:00:00

  • Effect of chronic graft-versus-host disease on the intestine in adult BDF1 mice.

    abstract::This study was performed to characterize the intestinal lesions in chronic graft-versus-host disease (GVHD) in mice and to determine a possible role of intestinal intraepithelial lymphocytes (ilEL) in the development of these lesions. Chronic GVHD was induced by transfer of DBA/2 lymphocytes into non-irradiated (C57BL...

    journal_title:International journal of experimental pathology

    pub_type: 杂志文章

    doi:

    authors: de Geus B,Hogenesch H,de Heer E,Bruijn JA,van den Enden M,Rozing J

    更新日期:1993-08-01 00:00:00

  • A "Western Diet" promotes symptoms of hepatic steatosis in spontaneously hypertensive rats.

    abstract::Systemic hypertension, characterized by elevated blood pressure ≥140/90 mm Hg, is a major modifiable risk factor for cardiovascular disease. Hypertension also associates with non-alcoholic fatty liver disease (NAFLD), which is becoming common due to a modern diet and lifestyle. The aim of the present study was to exam...

    journal_title:International journal of experimental pathology

    pub_type: 杂志文章

    doi:10.1111/iep.12369

    authors: Cartland SP,Tamer N,Patil MS,Di Bartolo BA,Kavurma MM

    更新日期:2020-10-01 00:00:00

  • Cervical thymuses exist, but no cervical thymomas develop in thoracic thymoma-prone BUF rats.

    abstract::To confirm the existence of the cervical thymus and the development of cervical thymoma in thymoma-prone BUF/Mna (BUF) rats, we examined cervical organs and adjacent tissues, and thoracic thymic tissues of the three inbred strains, BUF, ACI/NMna (ACI), and WKY/NCrj (WKY), and 11 congenic strains, in which genetic regi...

    journal_title:International journal of experimental pathology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2613.2010.00755.x

    authors: Yamada T,Matsuyama M,Yanagida T,Kato K,Sugiura S,Kuroda M

    更新日期:2011-04-01 00:00:00

  • A preliminary in vitro study into the use of IL-1Ra gene therapy for the inhibition of intervertebral disc degeneration.

    abstract::Conventional therapies for low back pain (LBP) are purely symptomatic and do not target the cause of LBP, which in approximately 40% of cases is caused by degeneration of the intervertebral disc (DIVD). Targeting therapies to inhibit the process of degeneration would be a potentially valuable treatment for LBP. There ...

    journal_title:International journal of experimental pathology

    pub_type: 杂志文章

    doi:10.1111/j.0959-9673.2006.00449.x

    authors: Le Maitre CL,Freemont AJ,Hoyland JA

    更新日期:2006-02-01 00:00:00

  • Immunohistochemical study of renal fibropoiesis associated with dogs naturally and experimentally infected with two different strains of Leishmania (L.) infantum.

    abstract::The objectives of this work were to study some pathological aspects of kidneys obtained from dogs naturally infected with Leishmania infantum and from dogs experimentally infected with two different strains of L infantum with special emphasis on fibrotic process. Seventy eight specimens of paraffin-embedded kidney fra...

    journal_title:International journal of experimental pathology

    pub_type: 杂志文章

    doi:10.1111/iep.12321

    authors: Alves AF,Pereira RA,de Andrade HM,Mosser DM,Tafuri WL

    更新日期:2019-08-01 00:00:00

  • Comparison of three research models of portal hypertension in mice: macroscopic, histological and portal pressure evaluation.

    abstract::The characterization of mice models of portal hypertension (PHT) is lacking in the literature. Therefore, the aim of the present study was to make a histological approach during development of PHT in two models of cirrhosis with PHT compared with one model of isolated PHT. The model of isolated PHT was developed by pa...

    journal_title:International journal of experimental pathology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2613.2008.00597.x

    authors: Geerts AM,Vanheule E,Praet M,Van Vlierberghe H,De Vos M,Colle I

    更新日期:2008-08-01 00:00:00

  • In vitro test to determine the effect of cytostatic drugs on co-cultured rat hepatocytes and hepatoma cells.

    abstract::Using uptake of the fluorescent bile acid derivative cholylglycylamido-fluorescein (FITC-GC) as a measurement of liver cell population size and function, the antiproliferative and toxic effects of the well known cytostatic drug, cisplatin was evaluated on rapidly growing rat hepatoma McA-RH7777 cells and rat hepatocyt...

    journal_title:International journal of experimental pathology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2613.1998.00054.x

    authors: El-Mir MY,Serrano MA,Macias RI,Dominguez MF,Monte MJ,Marin JJ

    更新日期:1998-04-01 00:00:00

  • Infiltration of polymorphonuclear cells into the post-ischaemic myocardium is dependent on beta2 and alpha4 integrins.

    abstract::Polymorphonuclear cells (PMN) are believed to be important effector cells responsible the myocardial damage seen following ischaemia. However, the exact kinetics of their migration remains controversial. Isolated PMN (10 x 10(6) cells) labelled with (51)Cr were injected into four groups of Lewis rats: 0 h (T0h; n = 13...

    journal_title:International journal of experimental pathology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2613.2007.00541.x

    authors: Légaré JF,Oxner A,Heimrath O,Issekutz T

    更新日期:2007-08-01 00:00:00

  • Hepatitis B virus and hepatocellular carcinoma.

    abstract::Chronic hepatitis B virus (HBV) infection is a major global cause of hepatocellular carcinoma (HCC). Individuals who are chronic carriers have a greater than 100-fold increased relative risk of developing the tumour. Several mechanisms of HBV-induced HCC have been proposed. Integration of HBV DNA into the genome of he...

    journal_title:International journal of experimental pathology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1365-2613.2001.iep0082-0077-x

    authors: Arbuthnot P,Kew M

    更新日期:2001-04-01 00:00:00

  • Collagen metabolism disturbances are accompanied by an increase in prolidase activity in lung carcinoma planoepitheliale.

    abstract::One of the consequences of neoplastic transformation is deregulation of tissue collagen metabolism. Although metalloproteinases initiate the breakdown of collagen in lung carcinoma, the final step of collagen degradation is mediated by prolidase (E.C.3.4.13.9). We investigated whether prolidase activity could reflect ...

    journal_title:International journal of experimental pathology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2613.2000.00168.x

    authors: Karna E,Surazynski A,Palka J

    更新日期:2000-10-01 00:00:00

  • Liver sinusoidal endothelial cells and acute non-oxidative hepatic injury induced by Pseudomonas aeruginosa pyocyanin.

    abstract::The liver sinusoidal endothelial cell (LSEC) is damaged by many toxins, including oxidants and bacterial toxins. Any effect on LSECs of the Pseudomonas aeruginosa virulence factor, pyocyanin, may be relevant for systemic pseudomonal infections and liver transplantation. In this study, the effects of pyocyanin on in vi...

    journal_title:International journal of experimental pathology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2613.2008.00602.x

    authors: Cheluvappa R,Cogger VC,Kwun SY,O'Reilly JN,Le Couteur DG,Hilmer SN

    更新日期:2008-12-01 00:00:00

  • Production of Heymann nephritis by a chemically modified renal antigen.

    abstract::An autoimmune kidney disease morphologically and functionally similar to Heymann nephritis (HN) was induced in mature male Sprague Dawley rats by repeated weekly IP injections of a chemically modified azo sonicated ultracentrifuged (u/c) rat kidney fraction 3 (rKF3) antigen in an aqueous medium. The experiment was ter...

    journal_title:International journal of experimental pathology

    pub_type: 杂志文章

    doi:10.1111/j.0959-9673.2004.00389.x

    authors: Barabas AZ,Cole CD,Barabas AD,Lafreniere R

    更新日期:2004-10-01 00:00:00

  • Transgenic overexpression of p23 induces spontaneous hydronephrosis in mice.

    abstract::p23 is a cochaperone of heat shock protein 90 and also interacts functionally with numerous steroid receptors and kinases. However, the in vivo roles of p23 remain unclear. To explore its in vivo function, we generated the transgenic (TG) mice ubiquitously overexpressing p23. The p23 TG mice spontaneously developed ki...

    journal_title:International journal of experimental pathology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2613.2011.00762.x

    authors: Lee J,Kim HJ,Moon JA,Sung YH,Baek IJ,Roh JI,Ha NY,Kim SY,Bahk YY,Lee JE,Yoo TH,Lee HW

    更新日期:2011-08-01 00:00:00