352 research outputs found
Possible Links between Intestinal Permeablity and Food Processing: A Potential Therapeutic Niche for Glutamine
Increased intestinal permeability is a likely cause of various pathologies, such as allergies and metabolic or even cardiovascular disturbances. Intestinal permeability is found in many severe clinical situations and in common disorders such as irritable bowel syndrome. In these conditions, substances that are normally unable to cross the epithelial barrier gain access to the systemic circulation. To illustrate the potential harmfulness of leaky gut, we present an argument based on examples linked to protein or lipid glycation induced by modern food processing. Increased intestinal permeability should be largely improved by dietary addition of compounds, such as glutamine or curcumin, which both have the mechanistic potential to inhibit the inflammation and oxidative stress linked to tight junction opening. This brief review aims to increase physician awareness of this common, albeit largely unrecognized, pathology, which may be easily prevented or improved by means of simple nutritional changes
Apnéia obstrutiva do sono e resistência à insulina: qual o papel da microcirculação?
Obstructive sleep apnea is an increasingly recognized medical problem. The recent attention to its frequency in the general population and its important role in metabolic, vascular, and behavioral aspects have sharply increased the number and nature of investigations, thereby revealing new aspects that open new approaches in research. Whereas obstructive sleep apnea is a well-known phenomenon accompanying obesity and diabetes, new findings strongly suggest that this close relationship may also operate in the opposite direction. Indeed obstructive sleep apnea may be a primary feature inducing or aggravating a series of vascular and metabolic disturbances closely resembling the metabolic syndrome. This review will discuss established and potential mechanisms responsible for these changes. Obstructive sleep apnea indeed appears to gather all the elements necessary to induce insulin resistance, hypertension, and possibly heart failure. After careful analysis of these modifications and considering how they are intertwined, we propose that microcirculation could represent the common denominator mediating the progression of this pathology, as it is eventually the case in the metabolic syndrome and diabetes domain. This plausible hypothesis is discussed in detail and should be verified by appropriate preclinical and clinical protocols, which are now achievable by using noninvasive techniques in humans.A apnéia obstrutiva do sono é um problema médico cujo reconhecimento tem aumentado. As últimas pesquisas mostrando sua freqüência na população em geral e seu importante papel metabólico, vascular e comportamental aumentou o número e a natureza das investigações revelando, assim, novos aspectos que abrem caminhos para estudos. Embora a apnéia obstrutiva do sono seja um fenômeno bem conhecido acompanhando diabetes e obesidade, novas descobertas sugerem que esta relação causal pode também ser verdadeira no sentido inverso. Na realidade, a apnéia obstrutiva do sono pode ser o marco inicial ou primário que induz ou agrava uma série de distúrbios vasculares e metabólicos que se aproximam da síndrome metabólica. Esta revisão discutirá mecanismos estabelecidos e potenciais responsáveis por estas mudanças. A apnéia obstrutiva do sono parece realmente juntar todos os elementos necessários para induzir resistência à insulina, hipertensão e possivelmente insuficiência cardíaca. Após análise cuidadosa destas modificações, considerando que as mesmas são interligadas, propomos que a microcirculação, como ocorre nos casos de síndrome metabólica e diabetes, poderia representar o denominador comum que mediaria a progressão desta patologia. Esta hipótese é discutida em detalhe e deve ser verificada em estudos pré-clínicos e clínicos apropriados que são atualmente possíveis usando técnicas não-invasivas em humanos
Fructose and Cardiometabolic Disorders: The Controversy Will, and Must, Continue
The present review updates the current knowledge on the question of whether high fructose consumption is harmful or not and details new findings which further pushes this old debate. Due to large differences in its metabolic handling when compared to glucose, fructose was indeed suggested to be beneficial for the diet of diabetic patients. However its growing industrial use as a sweetener, especially in soft drinks, has focused attention on its potential harmfulness, possibly leading to dyslipidemia, obesity, insulin resistance/metabolic syndrome and even diabetes. Many new data have been generated over the last years, confirming the lipogenic effect of fructose as well as risks of vascular dysfunction and hypertension. Fructose exerts various direct effects in the liver, affecting both hepatocytes and Kupffer cells and resulting in non-alcoholic steatotic hepatitis, a well known precursor of the metabolic syndrome. Hepatic metabolic abnormalities underlie indirect peripheral metabolic and vascular disturbances, for which uric acid is possibly the culprit
Short-Term Treatment with Metformin Improves the Cardiovascular Risk Profile in First-Degree Relatives of Subjects with Type 2 Diabetes Mellitus who have a Metabolic Syndrome and Normal Glucose Tolerance without Changes in C-Reactive Protein or Fibrinogen
OBJECTIVE: To study if metformin, when administered to first-degree relatives of type 2 diabetes mellitus subjects who have metabolic syndrome and normal glucose tolerance, could improve the cardiovascular risk profile and reduce the levels of both C-reactive protein and fibrinogen. INTRODUCTION: Metabolic syndrome is associated with higher cardiovascular morbidity and mortality. Metformin has vasculo-protective effects even in normoglycemic subjects, and C-reactive protein and fibrinogen are considered markers of endothelial injury and inflammation. METHODS: Thirty-one non-diabetic first-degree relatives of type 2 diabetes mellitus subjects with metabolic syndrome were randomized (1:1) and double-blinded for placement in the placebo and metformin groups (850mg bid/±90days); 16 subjects were administered metformin (mean age 40.0 [33.5-50] years; 13 females) and 15 subjects were in the placebo group (mean age 37.0 [32-42] years; 9 females). Blood samples were collected at baseline and at the end of treatment for biochemical analyses, including an assessment of C-reactive protein and fibrinogen levels. RESULTS: Metformin improved the lipid profile and decreased fasting plasma glucose, systolic blood pressure, weight and body mass index without changing body composition. For those in the placebo we identified no changes in fibrinogen (282.2 [220.4-323.7] mg/L vs. 286.7 [249.6-295.1] mg/L; NS) or in C-reactive protein levels (0.68 [0.3-1.2] vs. 0.64 [0.3-1.0] mg/L; NS). The same was also observed for the levels of fibrinogen (303.9 [217.6-347.6] mg/L vs. 290.9 [251.5-301.9] mg/L; NS) and C-reactive proteins (0.78 [0.3-1.1] vs. 0.80 [0.4-0.9] mg/L; NS) in the metformin group. CONCLUSIONS: Metformin treatment in first-degree relatives of type 2 diabetes mellitus sufferers who have metabolic syndrome and normal glucose tolerance improved the cardiovascular risk profile without changing the levels of C-reactive protein and fibrinogen
Substituição da água por solução de frutose induz hiperinsulinemia e hiperglicemia em hamster
PURPOSE: To test the possibility of obtaining a practical and stable model of hyperinsulinemia and hyperglycemia in hamsters, substituting the drinking water by 10% or 20% fructose solutions for a period of 2, 4, or 6 months. METHODS: Male hamsters were divided into 3 main groups, further divided in 3 subgroups: Two months: Group Ia control (n = 51) received filtered water, Group Ib (n = 49) received 10% fructose solution instead of water, Group Ic (n=8) received 20% fructose solution instead of water. Four months: Group IIa control (n=8), Group IIb 10% fructose (n = 7), Group IIc 20% fructose (FIIc, n = 7). Six months: Group IIIa control (n = 6), Group IIIb 10% Fructose (n = 6), Group IIIc 20% Fructose (n = 5). All groups were fed with the same laboratory diet. The animals were weighed every 2 weeks during the study period. On the final day of each experiment (61st, 121st, and 181st day after the beginning of the study, respectively), the animals were weighed and anesthetized for blood collection to determine plasma glucose and insulin after at least a 12-h fast. Ten animals of group Ia and 10 of group Ib were evaluated to determine changes in macromolecular permeability induced by ischemia/reperfusion as measured in the cheek pouch microcirculation. RESULTS: Compared to controls, the animals that drank the 10% or 20% fructose solution had significantly greater weight gain (P < .001), fasting plasma glucose (P < .001) Reperfusion, after 30 min ischemia, resulted in an immediate but reversible increase in postcapillary leakage (L) of 89.0 ± 2.0 L/cm² (group Ia - controls), and 116.5 ± 4.8 L/cm² (group Ib 10% fructose), P < .001.These results suggest that chronic administration of either 10% or 20% fructose solutions could be used to experimentally induce a stable hamster model of hyperinsulinemia and hyperglycemia. CONCLUSION: The model might facilitate the study of basic mechanisms of hyperglycemia and hyperinsulinemia affecting the microvasculature as demonstrated by the findings regarding ischemia/reperfusion after only 2 months of treatment.OBJETIVO: Testar a possibilidade de obtenção de um modelo prático e estável de hiperinsulinemia e hiperglicemia em hamsters substituindo a água de beber por soluções de frutose a 10% ou 20% por um período de dois, quatro ou seis meses. MÉTODOS: Hamsters machos foram divididos em 3 grupos e cada grupo subdividido em 3 subgrupos. Dois meses: Grupo Ia-controle (n=51), recebeu água filtrada, Grupo Ib-(n=49), recebeu solução de frutose a 10% ao invés de água e Grupo Ic-( n=8), recebeu solução de frutose a 20% ao invés de água. Quatro meses: Grupo IIa - controle (n=8), Grupo IIb - 10% frutose (n=7) e Grupo IIc - 20% frutose (n=7). Seis meses: Grupo IIIa - controle (n=6), Grupo IIIb - 10% frutose (n=6) e Grupo IIIc - 20% frutose (n=5). Todos os animais foram alimentados com a mesma dieta padrão de laboratório. Os animais foram pesados a cada 2 semanas durante o período do estudo. No dia do final do experimento (61º, 121º e 181º dia, respectivamente, após o início do estudo), os animais foram pesados e anestesiados para coleta de sangue para determinação da glicose e da insulina sérica, após jejum de pelo menos 12 h. Em 10 animais do grupo Ia e em 10 do grupo Ib avaliamos, na microcirculação da bolsa da bochecha, a variação da permeabilidade a macromoléculas induzida por isquemia/reperfusão. RESULTADOS: Comparados ao grupo controle, os animais que beberam soluções de frutose a 10 ou 20% tiveram um aumento significativo de massa corporal (
1,1-Dimethylbiguanidium(2+) dinitrate
In the crystal structure of the title compound, C4H13N5
2+·2NO3
−, the main intermolecular interactions are the N—H⋯O hydrogen bonds between the cationic amino groups and the O atoms of the nitrate ions. All amino H atoms and nitrate O atoms are involved in the three-dimensional hydrogen-bond network. There are two graph-set motifs R
2
2(8), which include the amino groups connected to the N atoms in the biguanide 3-, 4- and 5-positions, and the O atoms of a nitrate ion. They are extended along the a axis. An O atom of the second nitrate ion is involved in a graph-set motif C(4) that is a part of a helix-like N—H⋯O⋯H—N—H⋯O⋯ chain oriented along the b axis. There are also two weak C—H⋯O interactions in the crystal structure
Metformin improves skin capillary reactivity in normoglycaemic subjects with the metabolic syndrome
WSTĘP. Insulinooporność i rodzinne występowanie
cukrzycy niezależnie wiążą się z dysfunkcją śródbłonka.
Stres oksydacyjny odgrywa kluczową rolę w patofizjologii
uszkodzenia naczyń krwionośnych. Metformina,
oprócz obniżania stężenia glukozy, działa
ochronnie na naczynia. Celem niniejszej pracy by³o
zbadanie, czy metformina korzystnie wpływa na krążenie w odżywczych naczyniach włosowatych skóry
oraz czy zmniejsza stres oksydacyjny u osób wysokiego
ryzyka wystąpienia cukrzycy typu 2 i chorób
sercowo-naczyniowych.
METODY. Badaniem objęto 30 pacjentów z prawidłowym
stężeniem glukozy i zespołem metabolicznym
(MS), którzy mieli krewnych chorych na cukrzycę typu
2. średni wiek wynosił 39,1 ± 8,4 roku, a wskaźnik
masy ciała (BMI) 35,8 ± 4,8 kg/m2 (średnia ± odchylenie
standardowe). Pacjentów losowo podzielono
na 2 grupy za pomocą metody podwójnie œlepej próby w stosunku 1:1 - 14 osób otrzymywało placebo,
a 16 metforminę (1700 mg/d.). Wyjściowo
i po zakończeniu badania pobrano krew do analizy
biochemicznej oraz mocz w celu określenia stężenia
8-epi-prostaglandyny F2α (8-epi-PGF2α). Krążenie
w naczyniach włosowatych oceniano za pomocą wideokapilaroskopii
obrąbka naskórkowego, podczas
której analizowano średnicę pętli naczyń włosowatych
doprowadzających (AF), odprowadzających (EF)
i wierzchołkowych (AP), funkcjonalną gęstość naczyń
włosowatych (FCD), prędkość przepływu czerwonych
ciałek krwi w spoczynku (RBCV) oraz po 1 minucie
od okluzji naczyń tętniczych (RBCVmax), a także czas
potrzebny do jej osiągnięcia (TRBCVmax).
WNIOSKI. Metformina poprawiła reaktywność naczyń włosowatych skóry u osób z prawidłową glikemią i zespołem metabolicznym, niezależnie od zmian
stężenia 8-epi-PGF2α.AIMS. Insulin resistance and a parental history of
diabetes mellitus are independently associated with
endothelial dysfunction. Oxidative stress has a pivotal
role in the pathophysiology of vascular injury.
Metformin, in addition to its glucose-lowering properties,
has vasculoprotective effects. We investigated
whether metformin has beneficial effects on the
nutritive skin capillary circulation and deceases oxidative
stress in a group at high risk for type 2 diabetes
mellitus (T2DM) and cardiovascular disease.
METHODS. Thirty normoglycaemic subjects with the
metabolic syndrome (MS), who had first-degree relatives
with T2DM, participated. The mean age was
39.1 ± 8.4 years and body mass index (BMI) 35.7 ±
± 4.8 kg/m2 (mean ± SD). Subjects were randomized
1:1 to receive placebo (n = 14) or metformin
(n = 16; 1700 mg/day) in a double-blind study. At baseline and post treatment, blood and urine samples
were collected for biochemical and 8-epi-prostaglandin
F2α (8-epi-PGF2α) analysis, respectively.
Microcirculation was assessed by nailfold videocapillaroscopy,
analysing afferent (AF), efferent (EF) and
apical (AP) diameters of capillary loops, functional
capillary density (FCD), red blood cell velocity at rest
(RBCV), after 1 min arterial occlusion (RBCVmax) and
time (TRBCVmax) taken to reach it.
RESULTS. Groups did not differ significantly in anthropometric,
clinical, laboratory or microvascular measurements
at baseline. In the metformin group,
weight, BMI, systolic blood pressure and fasting plasma
glucose fell, and lipid profile and microcirculatory
parameters FCD, AF, EF, AP, RBCVmax and TRBCVmax
improved (all p < 0.01). No relationship between
clinico-laboratory parameters and microvascular
reactivity was observed, except for changes in total
and lowdensity lipoprotein-cholesterol and
RBCVmax. 8-epi-PGF2α did not change significantly
in either group.
CONCLUSIONS. Metformin improved skin capillary
reactivity in normoglycaemic MS subjects independently
of significant changes in 8-epi-PGF2α levels
Management of Diabetes Mellitus: Could Simultaneous Targeting of Hyperglycemia and Oxidative Stress Be a Better Panacea?
The primary aim of the current management of diabetes mellitus is to achieve and/or maintain a glycated hemoglobin level of ≤6.5%. However, recent evidence indicates that intensive treatment of hyperglycemia is characterized by increased weight gain, severe hypoglycemia and higher mortality. Besides, evidence suggests that it is difficult to achieve and/or maintain optimal glycemic control in many diabetic patients; and that the benefits of intensively-treated hyperglycemia are restricted to microvascular complications only. In view of these adverse effects and limitations of intensive treatment of hyperglycemia in preventing diabetic complications, which is linked to oxidative stress, this commentary proposes a hypothesis that “simultaneous targeting of hyperglycemia and oxidative stress” could be more effective than “intensive treatment of hyperglycemia” in the management of diabetes mellitus
Comparison of Antioxidant Effects of Honey, Glibenclamide, Metformin, and Their Combinations in the Kidneys of Streptozotocin-Induced Diabetic Rats
Hyperglycemia-induced increase in oxidative stress is implicated in diabetic complications. This study investigated the effect of metformin and/or glibenclamide in combination with honey on antioxidant enzymes and oxidative stress markers in the kidneys of streptozotocin (60 mg/kg; intraperitoneal)-induced diabetic rats. Diabetic rats were randomized into eight groups of five to seven rats and received distilled water (0.5 mL); honey (1.0 g/kg); metformin (100 mg/kg); metformin (100 mg/kg) and honey (1.0 g/kg); glibenclamide (0.6 mg/kg); glibenclamide (0.6 mg/kg) and honey (1.0 g/kg); metformin (100 mg/kg) and glibenclamide (0.6 mg/kg); or metformin (100 mg/kg), glibenclamide (0.6 mg/kg) and honey (1.0 g/kg) orally once daily for four weeks. Malondialdehyde (MDA) levels, glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were significantly elevated while catalase (CAT) activity, total antioxidant status (TAS), reduced glutathione (GSH), and GSH:oxidized glutathione (GSSG) ratio was significantly reduced in the diabetic kidneys. CAT, glutathione reductase (GR), TAS, and GSH remained significantly reduced in the diabetic rats treated with metformin and/or glibenclamide. In contrast, metformin or glibenclamide combined with honey significantly increased CAT, GR, TAS, and GSH. These results suggest that combination of honey with metformin or glibenclamide might offer additional antioxidant effect to these drugs. This might reduce oxidative stress-mediated damage in diabetic kidneys
Metformin:historical overview
Metformin (dimethylbiguanide) has become the preferred first-line oral blood glucose-lowering agent to manage type 2 diabetes. Its history is linked to Galega officinalis (also known as goat's rue), a traditional herbal medicine in Europe, found to be rich in guanidine, which, in 1918, was shown to lower blood glucose. Guanidine derivatives, including metformin, were synthesised and some (not metformin) were used to treat diabetes in the 1920s and 1930s but were discontinued due to toxicity and the increased availability of insulin. Metformin was rediscovered in the search for antimalarial agents in the 1940s and, during clinical tests, proved useful to treat influenza when it sometimes lowered blood glucose. This property was pursued by the French physician Jean Sterne, who first reported the use of metformin to treat diabetes in 1957. However, metformin received limited attention as it was less potent than other glucose-lowering biguanides (phenformin and buformin), which were generally discontinued in the late 1970s due to high risk of lactic acidosis. Metformin's future was precarious, its reputation tarnished by association with other biguanides despite evident differences. The ability of metformin to counter insulin resistance and address adult-onset hyperglycaemia without weight gain or increased risk of hypoglycaemia gradually gathered credence in Europe, and after intensive scrutiny metformin was introduced into the USA in 1995. Long-term cardiovascular benefits of metformin were identified by the UK Prospective Diabetes Study (UKPDS) in 1998, providing a new rationale to adopt metformin as initial therapy to manage hyperglycaemia in type 2 diabetes. Sixty years after its introduction in diabetes treatment, metformin has become the most prescribed glucose-lowering medicine worldwide with the potential for further therapeutic applications
- …