scholarly journals An Emerging Role of Glucagon-Like Peptide-1 in Preventing Advanced-Glycation-End-Product-Mediated Damages in Diabetes

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Alessandra Puddu ◽  
François Mach ◽  
Alessio Nencioni ◽  
Giorgio Luciano Viviani ◽  
Fabrizio Montecucco
Keyword(s):  
Type 2 Diabetes ◽  
Cell Function ◽  
Glucagon Secretion ◽  
Advanced Glycation ◽  
Chronic Hyperglycemia ◽  
Gut Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 (GLP-1) is a gut hormone produced in the intestinal epithelial endocrine L cells by differential processing of the proglucagon gene. Released in response to the nutrient ingestion, GLP-1 plays an important role in maintaining glucose homeostasis. GLP-1 has been shown to regulate blood glucose levels by stimulating glucose-dependent insulin secretion and inhibiting glucagon secretion, gastric emptying, and food intake. These antidiabetic activities highlight GLP-1 as a potential therapeutic molecule in the clinical management of type 2 diabetes, (a disease characterized by progressive decline of beta-cell function and mass, increased insulin resistance, and final hyperglycemia). Since chronic hyperglycemia contributed to the acceleration of the formation of Advanced Glycation End-Products (AGEs, a heterogeneous group of compounds derived from the nonenzymatic reaction of reducing sugars with free amino groups of proteins implicated in vascular diabetic complications), the administration of GLP-1 might directly counteract diabetes pathophysiological processes (such as pancreaticβ-cell dysfunction). This paper outlines evidence on the protective role of GLP-1 in preventing the deleterious effects mediated by AGEs in type 2 diabetes.

Novel Approaches to the Treatment of Type 2 Diabetes

2009 ◽  
Vol 22 (3) ◽  
pp. 320-332 ◽  
Author(s):  
Erin L. St. Onge ◽  
Shannon A. Miller ◽  
James R. Taylor
Keyword(s):  
Type 2 Diabetes ◽  
Cell Function ◽  
Glucagon Secretion ◽  
Current Evidence ◽  
Β Cell Function ◽  
Dipeptidyl Peptidase Iv Inhibitors ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Third Line

The emergence of the glucoregulatory hormone, glucagon-like peptide-1, has expanded our understanding of glucose homeostasis. The glucoregulatory actions of glucagon-like peptide-1 include enhancement of glucose-dependent insulin secretion, suppression of inappropriately elevated glucagon secretion, slowing of gastric emptying, and reduction of food intake. Two approaches have been developed to potentiate the effects of glucagon-like peptide-1 in those with type 2 diabetes. The glucagon-like peptide-1 analogs, such as exenatide, and dipeptidyl peptidase-IV inhibitors, such as sitagliptin, are currently available whereas others are in the final stages of development. These agents effectively reduce hemoglobin A1c while providing the other benefits associated with increased glucagon-like peptide-1. They also offer the potential to preserve the β-cell function. The effects on cardiovascular disease, if any, are unknown. Based on the current evidence, these agents represent viable second-and third-line options in the management of type 2 diabetes.

Subcutaneous glucagon-like peptide-1 (7-36) amide is insulinotropic and can cause hypoglycaemia in fasted healthy subjects

1998 ◽  
Vol 95 (6) ◽  
pp. 719-724 ◽  
Author(s):  
C. Mark B. EDWARDS ◽  
Jeannie F. TODD ◽  
Mohammad A. GHATEI ◽  
Stephen R. BLOOM
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Plasma Glucose ◽  
Healthy Subjects ◽  
Therapeutic Potential ◽  
Double Blind ◽  
Gut Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

1. Glucagon-like peptide-1 (7-36) amide (GLP-1) is a gut hormone released postprandially that stimulates insulin secretion, suppresses glucagon secretion and delays gastric emptying. The insulinotropic action of GLP-1 is more potent under hyperglycaemic conditions. Several published studies have indicated the therapeutic potential of subcutaneous GLP-1 in non-insulin-dependent (Type 2) diabetes mellitus. 2. We investigated whether subcutaneous GLP-1, at a dose shown to improve glycaemic control in early Type 2 diabetes, is insulinotropic at normal fasting glucose concentrations. A double-blind, randomized, crossover study of 10 healthy subjects injected with GLP-1 or saline subcutaneously after a 16 h fast was performed. The effect on cardiovascular parameters was also examined. 3. GLP-1 caused a near 5-fold rise in plasma insulin concentration. After treatment with GLP-1, circulating plasma glucose concentrations fell below the normal range in all subjects. One subject had symptoms of hypoglycaemia after GLP-1. A rise in pulse rate was found which correlated with the fall in plasma glucose concentration. An increase in blood pressure occurred with GLP-1 injection which was seen at the same time as the rise in plasma GLP-1 concentrations. 4. This study indicates that subcutaneous GLP-1 can override the normal homoeostatic mechanism maintaining fasting plasma glucose in man, and is also associated with an increase in blood pressure.

scholarly journals The Clinical Efficacy and Safety of Glucagon-Like Peptide-1 (GLP-1) Agonists in Adults with Type 2 Diabetes Mellitus

2011 ◽  
Vol 4 ◽  
pp. CMED.S4086 ◽  
Author(s):  
Kira R. Brice ◽  
Maria K. Tzefos
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Cell Function ◽  
Efficacy And Safety ◽  
Medline Search ◽  
Study Selection ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Objective To review the efficacy and safety of glucagon-like peptide-1 (GLP-1) agonists to determine their role in type 2 diabetes mellitus (T2DM). Data Sources A Medline search was conducted using the keywords exenatide, liraglutide, glucagon-like peptide-1, type 2 diabetes mellitus, hyperglycemia, pharmacokinetics, pharmacology and safety. Study Selection All identified articles written in English were evaluated with priority given to controlled, randomized trials including human data. References of identified published trials were reviewed for additional trials to be included in the review. Data Synthesis Exenatide and liraglutide are GLP-1 agonists approved for the treatment of T2DM. Several randomized, active and placebo controlled trials examining the efficacy and safety of exenatide and liraglutide both as monotherapy and in combination therapy have been conducted. Both agents have demonstrated improved glycemic control in addition to weight loss and increased beta-cell function. The most common adverse effects are gastrointestinal in nature and appear to be transient. Conclusion It appears exenatide and liraglutide are safe and effective in the treatment of T2DM and may exhibit effects that make them preferred over other anti-diabetic medications.

The Old and the New in the Treatment of Type 2 Diabetes: Focus on the Combination Therapy with Dipeptidyl Peptidase-4 Inhibitors and Metformin

2010 ◽  
Vol 2 ◽  
pp. CMT.S3420 ◽  
Author(s):  
Giovanni Anfossi ◽  
Isabella Russo ◽  
Katia Bonomo ◽  
Mariella Trovati
Keyword(s):  
Type 2 Diabetes ◽  
Cell Function ◽  
Microvascular Complications ◽  
Chronic Complications ◽  
Dipeptidyl Peptidase 4 ◽  
Chronic Hyperglycemia ◽  
Oral Agents ◽  
Dipeptidyl Peptidase 4 Inhibitors

Type 2 diabetes mellitus (T2DM) is a complex multifactorial disease which affects the length and quality of life by severe chronic complications. Chronic hyperglycemia, which is the main alteration in T2DM, is strictly related to microvascular complications (such as retinopathy and nephropathy) and neuropathy, whereas large vessel atherosclerosis is also dependent on lipid and hemostasis abnormalities, arterial hypertension and other known cardiovascular risk factors. An early intervention to control hyperglycemia and to prevent deterioration of β-cell function is considered mandatory in patients with T2DM to minimize the risk of chronic complications. Recently, the availability of new pharmacological agents with different targets, including the activation of the incretin system has allowed the proposal of more effective strategies for early treatment of metabolic alterations in patients with T2DM. This commentary will focus on the role of new oral agents influencing the incretin system and the putative advantages of their co-administration with metformin, an old, effective anti-hyperglycemic agent also able to exert beneficial actions on arterial vessels, reducing the risk of macrovascular-related events. The vasoprotective role of metformin is largely independent of its hypoglycemic action, and has been ascribed to pleiotropic effects.

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