Metformin and the gastrointestinal tract.


:Metformin is an effective agent with a good safety profile that is widely used as a first-line treatment for type 2 diabetes, yet its mechanisms of action and variability in terms of efficacy and side effects remain poorly understood. Although the liver is recognised as a major site of metformin pharmacodynamics, recent evidence also implicates the gut as an important site of action. Metformin has a number of actions within the gut. It increases intestinal glucose uptake and lactate production, increases GLP-1 concentrations and the bile acid pool within the intestine, and alters the microbiome. A novel delayed-release preparation of metformin has recently been shown to improve glycaemic control to a similar extent to immediate-release metformin, but with less systemic exposure. We believe that metformin response and tolerance is intrinsically linked with the gut. This review examines the passage of metformin through the gut, and how this can affect the efficacy of metformin treatment in the individual, and contribute to the side effects associated with metformin intolerance.






McCreight LJ,Bailey CJ,Pearson ER




Has Abstract


2016-03-01 00:00:00














  • HepG2/erythrocyte glucose transporter (GLUT1) gene in NIDDM: a population association study and molecular scanning in Japanese subjects.

    abstract::To evaluate the role of mutations in the glucose transporter (GLUT1) gene in Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM), we first conducted a population association study using the XbaI polymorphism of the gene. A polymerase chain reaction (PCR)-based assay was developed and used for the an...


    pub_type: 杂志文章


    authors: Tao T,Tanizawa Y,Matsutani A,Matsubara A,Kaneko T,Kaku K

    更新日期:1995-08-01 00:00:00

  • Vanadate treatment rapidly improves glucose transport and activates 6-phosphofructo-1-kinase in diabetic rat intestine.

    abstract::The effect of oral vanadate on intestinal sodium-dependent glucose transport and 6-phosphofructo-1-kinase (EC activity was examined in male Sprague-Dawley rats following a 30-day period of non-treated streptozotocin-induced diabetes. Non-treated diabetic rats were hyperglycaemic and demonstrated increased in...


    pub_type: 杂志文章


    authors: Madsen KL,Ariano D,Fedorak RN

    更新日期:1995-04-01 00:00:00

  • Pioglitazone-induced increase of insulin sensitivity in the muscles of the obese Zucker fa/fa rat cannot be explained by local adipocyte differentiation.

    abstract::Thiazolidinediones are potent antidiabetic compounds, which act by enhancing peripheral insulin sensitivity. They are also activators of the peroxisome proliferator activated receptor gamma in adipose tissue. Pioglitazone induces in vivo adipocyte differentiation in the obese Zucker fa/fa rat and hence the capacity of...


    pub_type: 杂志文章


    authors: Hallakou S,Foufelle F,Doaré L,Kergoat M,Ferré P

    更新日期:1998-08-01 00:00:00

  • Diabetes and pregnancy: national trends over a 15 year period.

    abstract:AIMS/HYPOTHESIS:We aimed to examine time trends in national perinatal outcomes in pregnancies complicated by pre-existing type 1 or type 2 diabetes. METHODS:We analysed episode-level data on all obstetric inpatient delivery events (live or stillbirth) between 1 April 1998 and 31 March 2013 (n = 813,921) using the Scot...


    pub_type: 杂志文章


    authors: Mackin ST,Nelson SM,Kerssens JJ,Wood R,Wild S,Colhoun HM,Leese GP,Philip S,Lindsay RS,SDRN Epidemiology Group.

    更新日期:2018-05-01 00:00:00

  • Risk factors for renal failure: the WHO Mulinational Study of Vascular Disease in Diabetes.

    abstract:AIMS/HYPOTHESIS:We aimed to examine risk factors for, and differences in, renal failure in diabetic patients from 10 centres. METHODS:Risk factors for renal failure were examined in 3,558 diabetic patients who did not have renal disease at baseline in the WHO Multinational Study of Vascular Disease in Diabetes (WHO MS...


    pub_type: 杂志文章


    authors: Colhoun HM,Lee ET,Bennett PH,Lu M,Keen H,Wang SL,Stevens LK,Fuller JH

    更新日期:2001-09-01 00:00:00

  • Elevated serum vascular endothelial growth factor is associated with visceral fat accumulation in human obese subjects.

    abstract:AIMS/HYPOTHESIS:Adipose tissue expresses some bioactive molecules, which may be involved in the development of obesity-associated metabolic disorders and cardiovascular diseases. Vascular endothelial growth factor (VEGF) an important angiogenic factor is implicated in normal and pathological vessel formation. The aim o...


    pub_type: 杂志文章


    authors: Miyazawa-Hoshimoto S,Takahashi K,Bujo H,Hashimoto N,Saito Y

    更新日期:2003-11-01 00:00:00

  • The GCKR rs780094 polymorphism is associated with elevated fasting serum triacylglycerol, reduced fasting and OGTT-related insulinaemia, and reduced risk of type 2 diabetes.

    abstract:AIMS/HYPOTHESIS:Recent genome-wide association studies have suggested that a polymorphism in GCKR, the gene encoding the glucokinase regulatory protein, is involved in triacylglycerol regulation. Our aim was to examine in large-scale studies the common GCKR rs780094 polymorphism in relation to metabolic traits (mainly ...


    pub_type: 杂志文章


    authors: Sparsø T,Andersen G,Nielsen T,Burgdorf KS,Gjesing AP,Nielsen AL,Albrechtsen A,Rasmussen SS,Jørgensen T,Borch-Johnsen K,Sandbaek A,Lauritzen T,Madsbad S,Hansen T,Pedersen O

    更新日期:2008-01-01 00:00:00

  • Effective treatment of symptomatic diabetic polyneuropathy by high-frequency external muscle stimulation.

    abstract:AIMS/HYPOTHESIS:Diabetic distal symmetrical sensory polyneuropathy (DSP) affects 20-30% of diabetic patients. Transcutaneous electrical nerve stimulation (TENS) and electrical spinal cord stimulation have been proposed as physical therapies. We performed a controlled, randomised pilot trial to compare the effects of hi...


    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Reichstein L,Labrenz S,Ziegler D,Martin S

    更新日期:2005-05-01 00:00:00

  • Identification of four trp1 gene variants murine pancreatic beta-cells.

    abstract::Insulin secretion is stimulated by glucose, hormones and neurotransmitters. Both activation of a non-selective cation current and activation of a Ca2+ current in response to depletion of intracellular Ca2+ stores have been suggested to play a role in this stimulation. The properties of these currents resemble those re...


    pub_type: 杂志文章


    authors: Sakura H,Ashcroft FM

    更新日期:1997-05-01 00:00:00

  • Association of variants of transcription factor 7-like 2 (TCF7L2) with susceptibility to type 2 diabetes in the Dutch Breda cohort.

    abstract:AIM/HYPOTHESIS:A strong association between susceptibility to type 2 diabetes and common variants of transcription factor 7-like 2 (TCF7L2), encoding an enteroendocrine transcription factor involved in glucose homeostasis, has been reported in three different populations (Iceland, Denmark and USA) by Grant et al. We ai...


    pub_type: 杂志文章


    authors: van Vliet-Ostaptchouk JV,Shiri-Sverdlov R,Zhernakova A,Strengman E,van Haeften TW,Hofker MH,Wijmenga C

    更新日期:2007-01-01 00:00:00

  • Orosomucoid in urine predicts cardiovascular and over-all mortality in patients with Type II diabetes.

    abstract:AIMS/HYPOTHESIS:Urinary orosomucoid excretion rate is increased in a substantial proportion of patients with Type II (non-insulin-dependent) diabetes mellitus and normal urinary albumin excretion rate. The aim of this study was to determine whether increased urinary orosomucoid excretion rate is predictive of increased...


    pub_type: 杂志文章


    authors: Christiansen MS,Hommel E,Magid E,Feldt-Rasmussen B

    更新日期:2002-01-01 00:00:00

  • Ultrastructure of heart muscle in short-term diabetic rats: influence of insulin treatment.

    abstract::The ultrastructure of myocardium was examined in short-term diabetic rats. Morphometric analysis showed the volume of myocytic mitochondria, sarcoplasmic reticulum and lipid droplets to be significantly increased compared with those of control animals. Further measurements of mitochondria and sarcoplasmic reticulum in...


    pub_type: 杂志文章


    authors: Reinilä A,Akerblom HK

    更新日期:1984-09-01 00:00:00

  • Reduction of oxidative stress by oral N-acetyl-L-cysteine treatment decreases plasma soluble vascular cell adhesion molecule-1 concentrations in non-obese, non-dyslipidaemic, normotensive, patients with non-insulin-dependent diabetes.

    abstract::To assess in vivo effects of antioxidants on vascular cell adhesion molecule (VCAM)-1 expression, circulating soluble VCAM-1 and intraerythrocytic reduced glutathione (GSH) and GSH disulphide (GSSG) concentrations were evaluated in non-insulin-dependent diabetic patients without complications (9 men, 6 women, 48 +/- 6...


    pub_type: 临床试验,杂志文章,随机对照试验


    authors: De Mattia G,Bravi MC,Laurenti O,Cassone-Faldetta M,Proietti A,De Luca O,Armiento A,Ferri C

    更新日期:1998-11-01 00:00:00

  • Functional impairment and killing of human beta cells by enteroviruses: the capacity is shared by a wide range of serotypes, but the extent is a characteristic of individual virus strains.

    abstract:AIMS/HYPOTHESIS:Direct infection of beta cells could explain the diabetogenic effect of enteroviruses. Primary adult human beta cells are susceptible to coxsackievirus infections, which could result in impaired beta-cell function or cell death (coxsackieviruses B3, B4, B5) or both, or no apparent immediate adverse effe...


    pub_type: 杂志文章


    authors: Roivainen M,Ylipaasto P,Savolainen C,Galama J,Hovi T,Otonkoski T

    更新日期:2002-05-01 00:00:00

  • The low dose streptozotocin murine model of type 1 (insulin-dependent) diabetes mellitus: studies in vivo and in vitro of the modulating effect of sex hormones.

    abstract::The influence of sex on pancreatic islet B cell susceptibility to streptozotocin was studied in mice given multiple low doses of streptozotocin. Male C3 D2 F1 mice developed a steadily increasing blood glucose level after a lag period of about 3 weeks, in contrast to females who were resistant. Spleen cells from strep...


    pub_type: 杂志文章


    authors: Kromann H,Christy M,Lernmark A,Nedergaard M,Nerup J

    更新日期:1982-03-01 00:00:00

  • Impaired deformability of erythrocytes and neutrophils in children with newly diagnosed insulin-dependent diabetes mellitus.

    abstract:AIMS/HYPOTHESIS:Abnormal rheological properties of erythrocytes, leucocytes and plasma may have a role in the development of diabetic microangiopathy. We hypothesized that changed haemorrheological variables may already be found in children with onset diabetes. METHODS:Erythrocyte deformation (rheoscope), neutrophil d...


    pub_type: 杂志文章


    authors: Linderkamp O,Ruef P,Zilow EP,Hoffmann GF

    更新日期:1999-07-01 00:00:00

  • Kidney transplantation in type 1 (insulin-dependent) diabetic patients. Early glomerulopathy.

    abstract::The development of diabetic glomerulopathy in kidneys transplanted to diabetic patients was estimated in transplant biopsies and evaluated in relation to suspected clinical risk factors for diabetic nephropathy. Surgical biopsies were taken at baseline and at 24-36 months post-transplantation in 16 Type 1 (insulin-dep...


    pub_type: 杂志文章


    authors: Osterby R,Nyberg G,Hedman L,Karlberg I,Persson H,Svalander C

    更新日期:1991-09-01 00:00:00

  • Symptoms, signs and complications in newly diagnosed type 2 diabetic patients, and their relationship to glycaemia, blood pressure and weight.

    abstract:AIMS/HYPOTHESIS:To document the prevalence of typical diabetic symptoms, signs and complications in the diagnosis of type 2 diabetes mellitus, examine their pre-diagnostic duration, and analyse associations with glycaemic level, blood pressure (BP), and weight. METHODS:An epidemiological population-based study of 1137...


    pub_type: 杂志文章


    authors: Drivsholm T,de Fine Olivarius N,Nielsen AB,Siersma V

    更新日期:2005-02-01 00:00:00

  • Role of insulin resistance in the pathogenesis of NIDDM.

    abstract::The above discussion illustrating the multitude of variables which influence insulin sensitivity in normal subjects challenges the prevailing view that insulin sensitivity is genetically determined in patients with NIDDM. The lack of accurate quantitation of all determinants of insulin sensitivity in the cross-section...


    pub_type: 杂志文章,评审


    authors: Yki-Järvinen H

    更新日期:1995-12-01 00:00:00

  • Reclassification of asymptomatic beta cell autoimmunity: a critical perspective.

    abstract::Type 1 diabetes is an immune-mediated disease leading to almost total beta cell destruction and permanent exogenous insulin dependency. The appearance of clinical symptoms is preceded by an asymptomatic preclinical period, the duration of which is highly individual. The emergence of diabetes-associated autoantibodies ...


    pub_type: 杂志文章


    authors: Knip M,Selvenius J,Siljander H,Veijola R

    更新日期:2017-01-01 00:00:00

  • Gangliosides in vivo reduce diabetes incidence in non-obese diabetic mice.

    abstract::Non-obese diabetic mice were treated daily with a mixture of gangliosides from day 30 until day 250 of life or until the mice became diabetic. Ganglioside treatment reduced diabetes incidence from 80-90% to 47% and from 20-30% to zero in female and male mice respectively. Gangliosides did not affect the frequency of p...


    pub_type: 杂志文章


    authors: Wilberz S,Herberg L,Renold AE

    更新日期:1988-11-01 00:00:00

  • Association between diabetes and haematological malignancies: a population-based study.

    abstract:AIMS/HYPOTHESIS:Contemporary data for the association of diabetes with haematological malignancies are lacking. We evaluated the risk of developing haematological malignancies and subsequent mortality in individuals with diabetes compared with those without diabetes. METHODS:We conducted a population-based observation...


    pub_type: 杂志文章


    authors: Gong IY,Cheung MC,Read S,Na Y,Lega IC,Lipscombe LL

    更新日期:2021-01-06 00:00:00

  • A proposal for the use of uniform diagnostic criteria for gestational diabetes in Europe: an opinion paper by the European Board & College of Obstetrics and Gynaecology (EBCOG).

    abstract::Screening and diagnostic criteria for gestational diabetes (GDM) are inconsistent across Europe, and the development of a uniform GDM screening strategy is necessary. Such a strategy would create opportunities for more women to receive timely treatment for GDM. Developing a consensus on screening for GDM in Europe is ...


    pub_type: 杂志文章


    authors: Benhalima K,Mathieu C,Damm P,Van Assche A,Devlieger R,Desoye G,Corcoy R,Mahmood T,Nizard J,Savona-Ventura C,Dunne F

    更新日期:2015-07-01 00:00:00

  • Continuous Glucose Monitoring System in children with type 1 diabetes mellitus: a systematic review and meta-analysis.

    abstract:AIMS/HYPOTHESIS:We investigated the potential effects of the Continuous Glucose Monitoring System (CGMS), as compared with self-monitoring of blood glucose, on glycaemic control in children with type 1 diabetes. METHODS:The following electronic databases were searched throughout June 2007: MEDLINE, EMBASE and The Coch...


    pub_type: 杂志文章,meta分析,评审


    authors: Golicki DT,Golicka D,Groele L,Pankowska E

    更新日期:2008-02-01 00:00:00

  • Renal hypertrophy in experimental diabetes: relation to severity of diabetes.

    abstract::Streptozotocin diabetic rats have larger kidneys than non-diabetic rats. In the present study the rate of kidney growth during the first seven days of diabetes was correlated with the blood glucose concentration. Over a wide range of blood glucose concentrations (116-340 mg/100 ml) the kidney weight, protein content a...


    pub_type: 杂志文章


    authors: Seyer-Hansen K

    更新日期:1977-04-01 00:00:00

  • Autoantibodies against sympathetic ganglia and evidence of cardiac sympathetic dysinnervation in newly diagnosed and long-term IDDM patients.

    abstract::To investigate the presence of autoantibodies against sympathetic nervous tissue and their correlation with cardiac sympathetic dysinnervation in insulin-dependent diabetes mellitus (IDDM), 20 newly diagnosed (age 26 +/- 6 years) and 48 long-term IDDM patients (age 40 +/- 13 years, duration of diabetes 22 +/- 12 years...


    pub_type: 杂志文章


    authors: Schsnell O,Muhr D,Dresel S,Tatsch K,Ziegler AG,Haslbeck M,Standl E

    更新日期:1996-08-01 00:00:00

  • Influence of protamine on adhesion, chemotaxis and proliferation of human vascular smooth muscle cells.

    abstract::It has been shown that, in streptozotocin diabetic rats, protamine-retarded insulin administered in vivo stimulates intimal hyperplasia in balloon-injured carotid artery. The aim of this study was to evaluate the influence of protamine on cultured human vascular smooth muscle cells (h VSMC), by observing its effects o...


    pub_type: 杂志文章


    authors: Cavalot F,Russo I,Mattiello L,Anfossi G,Massucco P,Mularoni E,Hahn AW,Trovati M

    更新日期:1997-01-01 00:00:00

  • Racial differences in incidence of juvenile-onset type 1 diabetes: epidemiologic studies in southern California.

    abstract::We have studied the epidemiologic characteristics of insulin-dependent (Type 1) diabetic patients aged 0-19 in a city (San Diego, southern California, USA) characterized by an impressive racial diversity and especially mild and constant climatic conditions. Ascertainment was through retrospective review of medical rec...


    pub_type: 杂志文章


    authors: Lorenzi M,Cagliero E,Schmidt NJ

    更新日期:1985-10-01 00:00:00

  • Enhanced VEGF signalling mediates cerebral neovascularisation via downregulation of guidance protein ROBO4 in a rat model of diabetes.

    abstract:AIMS/HYPOTHESIS:Diabetes promotes cerebral neovascularisation via increased vascular endothelial growth factor (VEGF) angiogenic signalling. Roundabout-4 (ROBO4) protein is an endogenous inhibitor of VEGF signalling that stabilises the vasculature. Yet, how diabetes affects ROBO4 function remains unknown. We hypothesis...


    pub_type: 杂志文章


    authors: Abdelsaid M,Coucha M,Hafez S,Yasir A,Johnson MH,Ergul A

    更新日期:2017-04-01 00:00:00

  • Functional alterations of G-proteins in diabetic rat retina: a possible explanation for the early visual abnormalities in diabetes mellitus.

    abstract::We examined changes in guanosine triphosphate-dependent signal transduction mechanisms in the retina from the early stages of the streptozotocin-diabetic rat, a model for Type 1 (insulin-dependent) diabetes mellitus. Guanosine triphosphate binding, guanosine triphosphatase activity, and binding of (azido) guanosine tr...


    pub_type: 杂志文章


    authors: Kowluru A,Kowluru RA,Yamazaki A

    更新日期:1992-07-01 00:00:00