Efectos reductores de la glucemia de las plantas nutracéuticas bolivianas

Introduction: The prevalence of diabetes type 2 is increasing worldwide, thus the search of novel alternative therapies is needed. According to their traditional use, we selected five Bolivian plants Chenopodium quinoa (CQ) Amaranthus caudatus (AC), Chenopodium pallidicaule (CP), Lupinus mutabilis (LM) and Smallanthus sonchifolius (SS) that are traditionally used to control glycemia. Methods: The effect of a single oral administration of Ethanolic (EtOH), hydro-ethanolic (EtOH70) and aqueous (Aq) extracts from all plant species were tested for their effect on blood glucose in non-fasted mice and during the oral glucose tolerance test (OGTT). The effect on insulin secretion was evaluated in mice pancreatic islets. Results: EtOH70 extracts of all the plants showed glucose-reducing effect at the highest dose evaluated (2000 mg/ kg b.w.). EtOH70 extracts improved the glucose tolerance evaluated by the OGTT in mice fasted for 12 hours. The extracts have different effects on glucose homeostasis since just extracts of AC, LM and CQ but not CP and SS increased insulin secretion as shown on mice pancreatic islets. The phytochemical qualitative characterization of EtOH70 extracts detected phenolic acids and flavonoids in AC, CP and CQ; alkaloids in LM and anthocyanidins in SS. None of EtOH70 extracts tested showed in vitro or in vivo acute toxicity at concentrations where they exhibit glucose lowering effects. Conclusions: We report here that extracts from AC, CQ, CP, LM and SS exhibit glucose lowering effect while just AC, CQ and LM stimulate directly the insulin secretion.Introducción: La prevalencia de diabetes tipo 2 está aumentando en todo el mundo, por lo que se necesita la búsqueda de nuevas terapias alternativas. Según su uso tradicional, seleccionamos cinco plantas bolivianas Chenopodium quinoa (CQ) Amaranthus caudatus (AC), Chenopodium pallidicaule (CP), Lupinus mutabilis (LM) y Smallanthus sonchifolius (SS) que se usan tradicionalmente para controlar la glucemia. Métodos: Se evaluó el efecto de la administración oral única de extractos etanólicos (EtOH), hidroetanólicos (EtOH70) y acuosos (Aq) de las plantas mencionadas para determinar su efecto sobre la glucosa en sangre en ratones en o sin ayunas y durante la prueba de tolerancia a la glucosa oral (PTGO). El efecto sobre la secreción de insulina se evaluó en islotes pancreáticos de ratones. Resultados: Los extractos de EtOH70 de todas las plantas disminuyeron la glucemia a la dosis más alta evaluada (2000 mg / kg b.w.). Los extractos de EtOH70 mejoraron la tolerancia a la glucosa evaluada mediante la PTGO en ratones con ayuno de 12 horas. Los extractos tienen diferentes efectos sobre la homeostasis de la glucosa, ya que solo los extractos de AC, LM y CQ pero no CP y SS aumentaron la secreción de insulina como se muestra en los islotes pancreáticos de los murinos. La caracterización cualitativa fitoquímica de extractos de EtOH70 detectó ácidos fenólicos y flavonoides en AC, CP y CQ, alcaloides en LM y antocianidinas en SS. Ninguno de los extractos de EtOH70 probados mostró toxicidad aguda in vitro o in vivo a concentraciones en las que exhiben efectos reductores de glucosa. Conclusión: Los extractos de AC, CQ, CP, LM y SS exhiben un efecto reductor de la glucosa, mientras que solo AC, CQ y LM estimulan directamente la secreción de insulina.Swedish International Development Cooperation Agency, SID

Long-term exposure to elemental constituents of particulate matter and cardiovascular mortality in 19 European cohorts: Results from the ESCAPE and TRANSPHORM projects

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Diabetes and Pre-Diabetes among Persons Aged 35 to 60 Years in Eastern Uganda : Prevalence and Associated Factors

Background: Our aim was to estimate the prevalence of abnormal glucose regulation (AGR) (i.e. diabetes and prediabetes) and its associated factors among people aged 35-60 years so as to clarify the relevance of targeted screening in rural Africa. Methods: A population-based survey of 1,497 people (786 women and 711 men) aged 35-60 years was conducted in a predominantly rural Demographic Surveillance Site in eastern Uganda. Participants responded to a lifestyle questionnaire, following which their Body Mass Index (BMI) and Blood Pressure (BP) were measured. Fasting plasma glucose (FPG) was measured from capillary blood using On-Call (R) Plus (Acon) rapid glucose meters, following overnight fasting. AGR was defined as FPG >= 6.1 mmol L-1 (World Health Organization (WHO) criteria or >= 5.6mmol L-1 (American Diabetes Association (ADA) criteria. Diabetes was defined as FPG >6.9mmol L-1, or being on diabetes treatment. Results: The mean age of participants was 45 years for men and 44 for women. Prevalence of diabetes was 7.4% (95% CI 6.1-8.8), while prevalence of pre-diabetes was 8.6% (95% CI 7.3-10.2) using WHO criteria and 20.2% (95% CI 17.5-22.9) with ADA criteria. Using WHO cut-offs, the prevalence of AGR was 2 times higher among obese persons compared with normal BMI persons (Adjusted Prevalence Rate Ratio (APRR) 1.9, 95% CI 1.3-2.8). Occupation as a mechanic, achieving the WHO recommended physical activity threshold, and higher dietary diversity were associated with lower likelihood of AGR (APRR 0.6, 95% CI 0.4-0.9; APRR 0.6, 95% CI 0.4-0.8; APRR 0.5, 95% CI 0.3-0.9 respectively). The direct medical cost of detecting one person with AGR was two US dollars with ADA and three point seven dollars with WHO cut-offs. Conclusions: There is a high prevalence of AGR among people aged 35-60 years in this setting. Screening for high risk persons and targeted health education to address obesity, insufficient physical activity and non-diverse diets are necessary

Meal intake increases circulating procoagulant microparticles in patients with type 1 and type 2 diabetes mellitus

Diabetes mellitus (DM) is associated with prothrombotic alterations, and postprandial hyperglycemia is an independent risk factor for cardiovascular complications. We therefore investigated whether a standardized mixed meal alters circulating microparticles (MPs) and their procoagulant activity in DM patients. Patients with DM type 1 (T1DM, n = 11) and type 2 (T2DM; n = 9) were studied before and 90 min after a standardized meal (without premeal insulin). MPs in plasma derived from platelets (PMPs), endothelial cells (EMPs), or monocytes (MMPs) were measured by flow cytometry. MP-induced thrombin generation in plasma was assessed by a calibrated automated thrombogram. In the fasting state, MPs did not differ significantly between T1DM and T2DM. Meal intake increased the following microparticles: PMPs expressing phosphatidylserine (by 55%, on average), P-selectin (by 86%), and tissue factor (TF; by 112%); EMPs expressing E-selectin (by 96%) and MMPs expressing TF (by 164%), with no significant group differences between T1DM and T2DM. There were no increments in EMPs expressing phosphatidylserine or TF. Meal intake increased MP-induced thrombin generation similarly in T1DM and T2DM with increased endogenous thrombin potential (p = 0.02) and peak thrombin (p = 0.03) and shortened time to peak (p = 0.02). Phosphatidylserine inhibition by lactadherin completely abolished MP-induced thrombin generation, while an anti-TF antibody had no effect. In conclusion, meal intake increased several types of circulating MPs in patients with diabetes mellitus. These MPs have a procoagulant potential, which is related to phosphatidylserine expression and negatively charged MP surfaces rather than to TF

Impaired Coupling of Glucose Signal to the Exocytotic Machinery in Diabetic GK Rats

The GK rat is a spontaneous model of NIDDM. The insulin response to 16.7 mmol/l glucose was markedly impaired in both isolated perfused pancreas and isolated islets from GK rats compared with control Wistar rats. Depolarization with 30 mmol/l KC1 in the presence of 3.3 mmol/l glucose and 250 μmol/l diazoxide induced similar insulin responses in perfused pancreases of GK and control rats. In contrast, the glucose-stimulated insulin release was also severely impaired in GK pancreases in the depolarized state. Forskolin (1 μmol/l) markedly enhanced insulin release at 3.3 mmol/l glucose in GK but not control pancreases (54 ± 15 vs. 3 ± 1 pmol/l0 min, P < 0.001). Dibutyryl cAMP (1 mmol/l) exerted effects similar to forskolin on insulin release in the perfused pancreas. In depolarized pancreases of GK but not control rats, forskolin also induced a marked insulin response at 3.3 mmol/l glucose (163 ± 48 vs. 16 ± 1 pmol/20 min,< P < 0.03). Similarly, in studies on isolated islets from GK rats cultured in 5.5 or 16.7 mmol/l glucose for 48 h, forskolin (5 μmol/l) restored insulin release in response to 16.7 mmol/l glucose but had no effect on islet glucose utilization at 3.3 or 16.7 mmol/l glucose. Forskolin markedly stimulated insulin release at 3.3 mmol/l glucose in GK but not control rat islets cultured for 48 h in 5.5 mmol/l glucose, whereas 20 mmol/l arginine had an almost identical effect in both islet varieties. However, in islets cultured in 16.7 mmol/l glucose, forskolin stimulated insulin release similarly both in control and GK islets at 3.3 mmol/l glucose. In conclusion, this study suggests that the insulinotropic effects of glucose are coupled to a direct regulation of the exocytotic machinery in the pancreatic 3-cell. This pathway is markedly impaired in GK rats, contributing to defective insulin response to glucose. In this model, cAMP generation restores the insulin response to 16.7 mmol/l glucose and exerts a marked insulin release even at 3.3 mmol/l glucose

Prevalence of abnormal glucose regulation by age category.

<p>Prevalence of abnormal glucose regulation by age category.</p

Early detection of type 2 diabetes in socioeconomically disadvantaged areas in Stockholm - comparing reach of community and facility-based screening

Background Type 2 diabetes and its high-risk stage, prediabetes, are often undiagnosed. Early detection of these conditions is of importance to avoid organ complications due to the metabolic disturbances associated with diabetes. Diabetes screening can detect persons unaware of diabetes risk and the elevated glucose levels can potentially be reversed through lifestyle modification and medication. There are mainly two approaches to diabetes screening: opportunistic facility-based screening at health facilities and community screening. Objective To determine the difference in population reach and participant characteristics between community- and facility-based screening for detection of type 2 diabetes and persons at high risk of developing diabetes. Methods Finnish diabetes risk score (FINDRISC) is a risk assessment tool used by two diabetes projects to conduct community- and facility-based screenings in disadvantaged suburbs of Stockholm. In this study, descriptive and limited inferential statistics were carried out analyzing data from 2,564 FINDRISC forms from four study areas. Community- and facility-based screening was compared in terms of participant characteristics and with population data from the respective areas to determine their reach. Results Our study found that persons born in Africa and Asia were reached through community screening to a higher extent than with facility-based screening, while persons born in Sweden and other European countries were reached more often by facility-based screening. Also, younger persons were reached more frequently through community screening compared with facility-based screening. Both types of screening reached more women than men. Conclusion Community-based screening and facility-based screening were complementary methods in reaching different population groups at high risk of developing type 2 diabetes. Community screening in particular reached more hard-to-reach groups with unfavorable risk profiles, making it a critical strategy for T2D prevention. More men should be recruited to intervention studies and screening initiatives to achieve a gender balance

Munc18b Increases Insulin Granule Fusion, Restoring Deficient Insulin Secretion in Type-2 Diabetes Human and Goto-Kakizaki Rat Islets with Improvement in Glucose Homeostasis

Reduced pancreatic islet levels of Munc18a/SNARE complex proteins have been postulated to contribute to the deficient glucose-stimulated insulin secretion (GSIS) in type-2 diabetes (T2D). Whereas much previous work has purported Munc18a/SNARE complex (Syntaxin-1A/VAMP-2/SNAP25) to be primarily involved in predocked secretory granule (SG) fusion, less is known about newcomer SGs that undergo minimal docking time at the plasma membrane before fusion. Newcomer SG fusion has been postulated to involve a distinct SM/SNARE complex (Munc18b/Syntaxin-3/VAMP8/SNAP25), whose levels we find also reduced in islets of T2D humans and T2D Goto-Kakizaki (GK) rats. Munc18b overexpression by adenovirus infection (Ad-Munc18b), by increasing assembly of Munc18b/SNARE complexes, mediated increased fusion of not only newcomer SGs but also predocked SGs in T2D human and GK rat islets, resulting in rescue of the deficient biphasic GSIS. Infusion of Ad-Munc18b into GK rat pancreas led to sustained improvement in glucose homeostasis. However, Munc18b overexpression in normal islets increased only newcomer SG fusion. Therefore, Munc18b could potentially be deployed in human T2D to rescue the deficient GSIS