incretins and Heart-Diseases

This review aimed to describe the potential mechanisms by which incretin hormones could mediate the relationship between glycemic index and cardiometabolic diseases. A body of evidence from many studies suggests that low glycemic index (GI) diets reduces the risk for type 2 diabetes and coronary heart disease. In fact, despite the extensive literature on this topic, the mechanisms underlying unfavorable effects of high GI foods on health remain not well defined. The postprandial and hormonal milieu could play a key role in the relationship between GI and cardiovascular risk. Incretin hormones, glucagon-like peptide1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are important regulators of postprandial homeostasis by amplifying insulin secretory responses. Response of GIP and GLP-1 to GI have been studied more in depth, also by several studies on isomaltulose, which have been taken as an ideal model to investigate the kinetics of incretin secretion in response to foods' GI. In addition, extrapancreatic effects of these incretin hormones were also recently observed. Emerging from this have been exciting effects on several targets, such as body weight regulation, lipid metabolism, white adipose tissue, cardiovascular system, kidney, and liver, which may importantly affect the health status.

Topics: Animals; Blood Glucose; Dietary Carbohydrates; Energy Metabolism; Glycemic Index; Heart Diseases; Humans; Incretins; Metabolic Diseases; Nutritional Status

Established therapies for type-2 diabetes effectively reduce blood glucose, but are often associated with adverse effects that pose risks to patient's health or diminish adherence to treatment. Weight gain, hypoglycaemia and gastrointestinal symptoms are commonly reported and some agents may not be safe for use in patients with renal impairment or elevated cardiovascular risk. New treatments based on the action of the endogenous human hormone glucagon-like peptide-1 (GLP-1), including exenatide and liraglutide, are available. These therapies provide a novel pharmacological approach to glycaemic control via multiple mechanisms of action, and accordingly exhibit different safety and tolerability profiles than conventional treatments. GLP-1 receptor agonists stimulate insulin release only in the presence of elevated blood glucose and are therefore associated with a fairly low risk of hypoglycaemia. Gastrointestinal symptoms are common but transient, and there appears to be little potential for interaction with other drugs. GLP-1 receptor agonists are associated with weight loss rather than weight gain. As protein-based therapies, these agents have the potential to induce antibody formation, but the impact on efficacy and safety is minor. GLP-1 receptor agonists thus offer a new and potentially useful option for clinicians concerned about some of the common adverse effects of type-2 diabetes therapies.

Topics: Chemical and Drug Induced Liver Injury; Diabetes Mellitus, Type 2; Drug Interactions; Gastrointestinal Diseases; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Heart Diseases; Humans; Hypoglycemia; Hypoglycemic Agents; Incretins; Insulin; Kidney Diseases; Pancreatitis; Receptors, Glucagon; Sulfonylurea Compounds; Thiazolidinediones; Thyroid Diseases

Glucagon-like peptide-1 receptor agonists may have a role in modulation of cardiac fibrosis. Our study aimed to determine the effect of the glucagon-like peptide-1 receptor agonist liraglutide in obesity, hypertension and age-induced murine models of cardiac fibrosis and identify associated molecular mechanisms.. C57Bl/6J mice on a high-fat diet and C57Bl/6J mice on a normal chow diet treated with angiotensin II were used to induce obesity and hypertension-mediated cardiac fibrosis, respectively. C57Bl/6J mice 20 months old were used to study age-induced cardiac fibrosis. Liraglutide treatment of 30 µg/kg/day-300 µg/kg s.c. twice daily was administered for 4 weeks.. Liraglutide treatment attenuated obesity, hypertension and age-induced increases in interstitial cardiac fibrosis and expression of inflammatory and oxidative stress markers.. These observations identify a potential role for liraglutide in the prevention of cardiac fibrosis and identify molecular mechanisms associated with these effects.

Topics: Aging; Angiotensin II; Animals; Aorta; Blood Pressure; Body Weight; Chemokine CCL2; Diet, High-Fat; Disease Models, Animal; Endothelium, Vascular; Fibrosis; Glucagon-Like Peptide-1 Receptor; Heart; Heart Diseases; Hypertension; I-kappa B Proteins; Immunohistochemistry; Incretins; Inflammation; Interleukin-10; Liraglutide; Macrophages; Male; Mice; Mice, Inbred C57BL; Myocardium; NF-kappa B p50 Subunit; Obesity; Oxidative Stress; Real-Time Polymerase Chain Reaction; Vasoconstrictor Agents; Vimentin

Topics: Animals; Blood Glucose; Cardiotonic Agents; Clinical Trials, Phase II as Topic; Delayed Diagnosis; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Global Health; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Heart Diseases; Humans; Hypoglycemic Agents; Incretins; Models, Animal; Receptors, Glucagon

The physiological effects of the incretin hormone glucagon-like peptide-(GLP-)1 have contributed to the important role that incretin-based therapies with GLP-1 analogs or dipeptidyl peptidase-(DPP-)4 inhibitors already play in type 2 diabetes treatment. This development is not only due to the glucose-dependent insulinotropic effect of GLP-1 as well as the positive effects on beta cell function and, probably, beta cell mass, but also to the beneficial effects on body weight.Lately, the data on positive cardiovascular effects of GLP-1 have been growing. In animal models, GLP-1 improves left ventricular function and diminishes myocardial defects in ischemia models. In clinical studies with GLP-1 analogs, a normalization of blood pressure was observed and some of the data from animal studies after myocardial infarction or after invasive cardiologic or cardiosurgical interventions were also found under clinical conditions in humans. Additionally, an improvement of cardiovascular surrogate parameters was observed with incretin-based therapies. This review gives an overview on the cardiovascular effects of GLP-1 and incretin-based therapies.

Topics: Animals; Diabetes Complications; Heart Diseases; Humans; Incretins; Models, Cardiovascular