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Free radicals are generated as byproduct of our body metabolism, and their adverse effect on normal functioning of our body is prevented by body's own antioxidant machinery. Any perturbation in the defense mechanism of antioxidants inside body, its abnormal production or its induction from environment to our body lead to serious threats and is responsible for the development of various neurodegenerative disorders (NDDs). Perturbed antioxidants result in sensory and functional impairments in neuronal cells, which in turn cause NDDs. Free radical attack on neuronal cells plays a catastrophic role in NDDs. Impaired metabolism and generation of excessive reactive oxygen species also lead to a range of NDDs. Free radical induced toxicity is responsible for DNA injury, protein degradation, damage to tissue inflammation and cell death. Besides various genetic and environmental factors, free radical induced oxidative stress is also a major cause of NDDs. Application of upstream and downstream antioxidant therapy to counter oxidative stress can be an effective option in alteration of any neuronal impairment besides free radical scavenging. In the present manuscript, we have presented a comprehensive update on the symptoms, causes and cures of NDDs in relation with their dynamic association with oxidative stress.

Glucagon-like peptide-1 (GLP-1) is an intestinal hormone that stimulates insulin secretion and decreases glucagon release. It has been hypothesized that GLP-1 also reduces glycemia independent of its effect on islet hormones. Based on preliminary evidence that GLP-1 has independent actions on endogenous glucose production, we undertook a series of experiments that were optimized to address this question. The effect of GLP-1 on glucose appearance (Ra) and glucose disposal (Rd) was measured in eight men during a pancreatic clamp that was performed by infusing octreotide to suppress secretion of islet hormones, while insulin and glucagon were infused at rates adjusted to maintain blood glucose near fasting levels. After stabilization of plasma glucose and equilibration of [3H]glucose tracer, GLP-1 was given intravenously for 60 min. Concentrations of insulin, C-peptide, and glucagon were similar before and during the GLP-1 infusion (115 +/- 14 vs. 113 +/- 11 pM; 0.153 +/- 0.029 vs. 0.156 +/- 0.026 nM; and 64.7 +/- 11.5 vs. 65.8 +/- 13.8 ng/l, respectively). With the initiation of GLP-1, plasma glucose decreased in all eight subjects from steady-state levels of 4.8 +/- 0.2 to a nadir of 4.1 +/- 0.2 mM. This decrease in plasma glucose was accounted for by a significant 17% decrease in Ra, from 22.6 +/- 2.8 to 19.1 +/- 2.8 micromol. kg-1. min-1 (P < 0.04), with no significant change in Rd. These findings indicate that, under fasting conditions, GLP-1 decreases endogenous glucose production independent of its actions on islet hormone secretion.

Objective: The purpose of this study was to determine whether an extended infusion of the incretin hormone glucagon-like peptide 1 (GLP-1) has a greater effect to promote insulin secretion in type 2 diabetic subjects than acute administration of the peptide., Research Design and Methods: Nine diabetic subjects and nine nondiabetic volunteers of similar age and weight were studied in identical protocols. First-phase insulin release (FPIR; the incremental insulin response in the first 10 min after the intravenous glucose bolus) and second-phase insulin release (SPIR; the incremental insulin response from 10-60 min after intravenous glucose) were measured during three separate intravenous glucose tolerance tests (IVGTTs): 1). without GLP-1 (control); 2). with acute administration of GLP-1 as a square wave starting just before glucose administration; and 3). with an extended infusion of GLP-1 for 3 h before and during the IVGTT., Results: In the subjects with diabetes, FPIR was severely impaired-a defect that was only modestly improved by acute administration of GLP-1 (197 +/- 97 vs. 539 +/- 218 pmol/l. min, P < 0.05), while SPIR was substantially increased (1952 +/- 512 vs. 8072 +/- 1664 pmol/l. min, P < 0.05). In contrast, the 3-h preinfusion of GLP-1 normalized fasting hyperglycemia (7.9 +/- 0.5 vs. 5.2 +/- 0.6, P < 0.05), increased FPIR by 5- to 6-fold (197 +/- 97 vs. 1141 +/- 409 pmol/l. min, P < 0.05), and augmented SPIR significantly (1952 +/- 512 vs. 4026 +/- 851 pmol/l. min, P < 0.05), but to a lesser degree than the acute administration of GLP-1. In addition, only the 3-h GLP-1 preinfusion significantly improved intravenous glucose tolerance (K(g) control 0.61 +/- 0.04, acute infusion 0.71 +/- 0.04, P = NS; 3-h infusion 0.92 +/- 0.08%/min, P < 0.05). These findings were also noted in the nondiabetic subjects in whom acute administration of GLP-1 significantly increased SPIR relative to the control IVGTT (9439 +/- 2885 vs. 31553 +/- 11660 pmol/l. min, P < 0.001) with less effect on FPIR (3221 +/- 918 vs. 4917 +/- 1614 pmol/l. min, P = 0.075), while the 3-h preinfusion of GLP-1 significantly increased both FPIR (3221 +/- 918 vs. 7948 +/- 2647 pmol/l. min, P < 0.01) and SPIR (9439 +/- 2885 vs. 21997 +/- 9849 pmol/l. min, P < 0.03)., Conclusions: Extended administration of GLP-1 not only augments glucose-stimulated insulin secretion, but also shifts the dynamics of the insulin response to earlier release in both diabetic and nondiabetic humans. The restitution of some FPIR in subjects with type 2 diabetes is associated with significantly improved glucose tolerance. These findings demonstrate the benefits of a 3-h infusion of GLP-1 on beta-cell function beyond those of an acute insulin secretagogue, and support the development of strategies using continuous or prolonged GLP-1 receptor agonism for treating diabetic patients.

Although glucocorticoid therapy carries a risk of promoting or exacerbating hyperglycemia, there are currently no established medical guidelines for detecting or managing diabetes in patients starting such therapy. The authors use three case reports to illustrate a relatively simple strategy that can be used to manage preexisting and new-onset diabetes in the primary care setting.