Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are incretin-derived glucose-lowering agents that have been used for the treatment of type 2 diabetes since 2007. Agents such as exenatide (short-acting and once weekly preparations), liraglutide, taspoglutide, albiglutide and lixisenatide lower fasting glucose and HbA 1c upon subcutaneous injection, leading to glycaemic control that is equivalent to, or better than, that observed with other oral glucose-lowering agents or bedtime insulin. However, varying proportions of patients report nausea and vomiting, adverse events that typically narrow the therapeutic dose range. Furthermore, GLP-1 RAs reduce fasting glucose to a clinically meaningful extent, but not into the normal range.
GLP-1: a parent compound for novel incretin-based glucose-lowering drugsGlucagon-like peptide-1 (GLP-1) has attracted attention because of its ability to stimulate insulin secretion in a glucose-dependent manner, to suppress glucagon release when glucose concentrations are not in the hypoglycaemic range, and to elicit a number of extra-pancreatic effects (on appetite/satiety, gastrointestinal motility and the cardiovascular system) [1]. This spectrum of biological activities addresses important deficits typical for patients with type 2 diabetes (impaired beta cell function, hyperglucagonaemia, overeating/obesity, excessive postprandial rises in glucoseElectronic supplementary material The online version of this article (doi:10.1007/s00125-013-2953-6) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
Vildagliptin and sitagliptin affected incretin hormones, glucose concentrations, insulin and glucagon secretion in a similar manner. Inter-individual variations in L-cell feedback inhibition may indicate heterogeneity in the clinical response to DPP-4 inhibition.
Sitagliptin, in patients already treated with a GLP-1 receptor agonist (liraglutide), increased intact GLP-1 and GIP concentrations, but with marginal, non-significant effects on glycaemic control. GLP-1 receptors have probably been maximally stimulated by liraglutide. Our findings do not support combination treatment with GLP-1 receptor agonists and DPP-4 inhibitors, but longer-term trials are needed to support clinical recommendations.
Abiotic stress significantly limits plant growth and production. Drought, in particular, is a severe constraint that affects growth and limits agricultural productivity on a global scale. Water stress induces in plants a set of morpho-anatomical (modification of root and leaf structure), physiological, and biochemical (relative water content, membrane stability, photosynthesis, hormonal balance, antioxidant systems, and osmolyte accumulation) changes mainly employed to cope with the drought stress. These strategies allow the plant to overcome the unfavorable period of limited water availability. Currently, a promising alternative is available to improve plant growth and tolerance under drought conditions. The use of osmotolerant plant growth-promoting rhizobacteria (PGPR) as inoculants can alleviate water stress by increasing the water use efficiency of the plant. The PGPR improve the tolerance of plants to drought, through changes in the morphology and architecture of the root system, production of phytohormones, extracellular polysaccharides, ACC 1-(aminocyclopropane-1-carboxylate) deaminase, volatile chemicals, and osmolyte accumulation. They may also enhance the antioxidant defense system and induce transcriptional regulation of stress response genes. This review addresses the effects of stress on plant growth, adaptation, and response to drought conditions and discusses the significant potential of PGPR to modulate the physiological response against water scarcity, ensuring plant survival and improving the resistance and growth of agricultural crops.
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