3 resultados para insulin, therapeutic use

em WestminsterResearch - UK


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Type 2 diabetes is a multifactorial metabolic disease characterized by defects in β-cells function, insulin sensitivity, glucose effectiveness and endogenous glucose production (1). It is widely accepted that insulin and exercise are potent stimuli for glucose transport (2). Acute exercise is known to promote glucose uptake in skeletal muscle via an intact contraction stimulated mechanism (3), while post-exercise improvements in glucose control are due to insulin-dependant mechanisms (2). Hypoxia is also known to promote glucose uptake in skeletal muscle using the contraction stimulated pathway. This has been shown to occur in vitro via an increase in β-cell function, however data in vivo is lacking. The aim of this study was to examine the effects of acute hypoxia with and without exercise on insulin sensitivity (SI2*), glucose effectiveness (SG2*) and β-cell function in individuals with type 2 diabetes. Following an overnight fast, six type 2 diabetics, afer giving informed written consent, completed 60 min of the following: 1) normoxic rest (Nor Rest); 2) hypoxic rest [Hy Rest; O2 = 14.6 (0.4)%]; 3) normoxic exercise (Nor Ex); 4) hypoxic exercise [Hy Ex; O2 = 14.6 (0.4)%]. Exercise trails were set at 90% of lactate threshold. Each condition was followed by a labelled intravenous glucose tolerance test (IVGTT) to provide estimations of SI2*, SG2* and β-cell function. Values are presented as means (SEM). Two-compartmental minimal model analysis showed SI2* to be higher following Hy Rest when comparisons were made with Nor Rest (P = 0.047). SI2* was also higher following Hy Ex [4.37 (0.48) x10-4 . min-1 (μU/ml)] compared to Nor Ex [3.24 (0.51) x10-4 . min-1 (μU/ml)] (P = 0.048). Acute insulin response to glucose (AIRg) was reduced following Hy Rest vs. Nor Rest (P = 0.014 - Table 1). This study demonstrated that 1) hypoxia has the ability to increase glucose disposal; 2) hypoxic-induced improvements in glucose tolerance in the 4 hr following exposure can be attributed to improvements in peripheral SI2*; 3) resting hypoxic exposure improves β-cell function and 4) exercise and hypoxia have an additive effect on SG2* in type 2 diabetics. These findings suggest a possible use for hypoxia both with and without exercise in the clinical treatment of type 2 diabetes.

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Type 2 diabetes is a metabolic disease categorized primarily by reduced insulin sensitivity, β-cell dysfunction, and elevated hepatic glucose production. Treatments reducing hyperglycemia and the secondary complications that result from these dysfunctions are being sought after. Two distinct pathways encourage glucose transport activity in skeletal muscle, ie, the contraction-stimulated pathway reliant on Ca2+/5′-monophosphate-activated protein kinase (AMPK)-dependent mechanisms and an insulin-dependent pathway activated via upregulation of serine/threonine protein kinase Akt/PKB. Metformin is an established treatment for type 2 diabetes due to its ability to increase peripheral glucose uptake while reducing hepatic glucose production in an AMPK-dependent manner. Peripheral insulin action is reduced in type 2 diabetics whereas AMPK signaling remains largely intact. This paper firstly reviews AMPK and its role in glucose uptake and then focuses on a novel mechanism known to operate via an insulin-dependent pathway. Inositol hexakisphosphate (IP6) kinase 1 (IP6K1) produces a pyrophosphate group at the position of IP6 to generate a further inositol pyrophosphate, ie, diphosphoinositol pentakisphosphate (IP7). IP7 binds with Akt/PKB at its pleckstrin homology domain, preventing interaction with phosphatidylinositol 3,4,5-trisphosphate, and therefore reducing Akt/PKB membrane translocation and insulin-stimulated glucose uptake. Novel evidence suggesting a reduction in IP7 production via IP6K1 inhibition represents an exciting therapeutic avenue in the treatment of insulin resistance. Metformin-induced activation of AMPK is a key current intervention in the management of type 2 diabetes. However, this treatment does not seem to improve peripheral insulin resistance. In light of this evidence, we suggest that inhibition of IP6K1 may increase insulin sensitivity and provide a novel research direction in the treatment of insulin resistance.

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Introduction: In the UK, common mental health disorders account for one in five of all work days lost, and cost employers £25bn each year. Herbal medicine has been shown to potentially be of use for mental distress, including conditions like anxiety. In 2008, 35% of British adults surveyed claimed to have used herbal medicine at some stage, the majority of whom were women. However, there is little research into how the users of western herbal medicine (WHM) experience the practice of herbal medicine, or how these experiences may change over time. Our research is studying women in the south-east of the UK who are suffering from distress (either as a primary complaint, or associated with another condition) who are seeking the services of a herbalist who practices WHM. Aim: To investigate the experiences of western herbal practice by women who are suffering with distress. Methods: The study is using semi-structured interviews of around thirty women, to elicit patient narratives at two time points. Thematic analysis is being used to consider how distressed women perceive and experience their distress, their reasons for using WHM, what contribution the women perceive the consultation and treatment with WHM may or may not make to their wellbeing, and whether their experiences change over time. Currently, sixteen women have been interviewed, and a preliminary thematic analysis has commenced. Results: Preliminary finding suggest that not only do women internalise their distress, but that they are surprisingly isolated in how they deal with it, whilst some also express social embarrassment about their experiences. The women perceived that their distress is not always considered seriously from their medical practitioners’ point of view. These women are drawn to herbalists not only in a search for effective treatment, but also to be given time to have their story heard, to form a collaborative relationship, and to attempt to regain some control of their life. The herbal treatment is valued due to its perceived naturalness, and reduced risk of adverse side effects. Nevertheless, WHM is just one of a number of self-care strategies that women utilise to help manage their distress. Discussion: Effective treatment is not only dependent upon the herbs, but also upon an effective therapeutic relationship. Feeling that the herbalist hears their story, provides a treatment plan that is individually tailored to the patient, and is available (even outside of the consultation) are all important in helping to establish this relationship.