title: Effect of GLP-1 based therapies on diabetic dyslipidemia.
abstract: Glucagon-like peptide-1 (GLP-1), is a hormone secreted by small intestine. Consumption of food or glucose stimulates synthesis and secretion of GLP-1 in the bloodstream, which in turn stimulates insulin secretion from pancreas and delays gastric emptying. Owing to the favorable spectrum of effects on reduction of hyperglycemia and body weight, GLP-1 mimetics are intensely pursued as therapies for the treatment of type 2 diabetes (T2DM). Even after intensive control of hyperglycemia, the propensity for cardiovascular disease cannot be totally negated in diabetic patients. A major reason for the cardiovascular disease risk in diabetic patients is underlying dyslipidemia, also termed as diabetic dyslipidemia. It is characterized by high concentrations of triglycerides and LDL cholesterol, and lowered HDL cholesterol in plasma, which are associated with hyperglycemia. Increased insulin resistance gives rise to increased free fatty acids in bloodstream, which is the main reason for the lipid changes appearing in diabetic dyslipidemia. The secondary complications like atherosclerosis and other cardiovascular diseases may be predicted with the blood concentrations of triglycerides and cholesterol, due to the correlation proven in clinic. Hence, new drugs that target diabetic dyslipidemia will always be useful in therapy. Apart from its actions on body weight and glucose, GLP-1 can also regulate cholesterol and triglycerides by numerous ways. Acute and long term treatment with either GLP-1 or its stable analogs reduced fasting as well as postprandial lipids in healthy as well as T2DM patients. GLP-1R signaling reduces VLDL-TG production rate from liver, reduces hepatic TG content by modulating key enzymes of lipid metabolism in liver, and impairs hepatocyte de novo lipogenesis and β-oxidation. GLP-1 can also modulate reverse cholesterol transport. Apart from these direct effects on lipid metabolism, GLP-1 also reduces atherosclerotic events by inhibiting expression of atherogenic inflammatory mediators, suppressing smooth muscle cell proliferation and stimulating NO production. This review mainly deliberates the association of GLP-1 in lipid regulation via lipid absorption, hepatic cholesterol metabolism, reverse cholesterol transport and progression of atherosclerosis.
authors.forename: Vishal J
authors.initials: VJ
authors.lastname: Patel
authors.forename: Amit A
authors.initials: AA
authors.lastname: Joharapurkar
authors.forename: Gaurang B
authors.initials: GB
authors.lastname: Shah
authors.affiliation: Department of Pharmacology and Toxicology, Zydus Research Centre, Sarkhej Bavla NH No. 8A, Moraiya, Ahmedabad 382210, India. amitjoharapurkar@zyduscadila.com.
authors.forename: Mukul R
authors.initials: MR
authors.lastname: Jain
mesh_terms: D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000097:blood / Q000517:prevention & control*; D050171:Dyslipidemias / Q000097:blood / Q000517:prevention & control*; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology* / Q000627:therapeutic use; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects; D018027:Receptors, Glucagon / Q000187:drug effects; D012307:Risk Factors; D015398:Signal Transduction; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
chemical_list: D000924:Anticholesteremic Agents; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D018027:Receptors, Glucagon; D014280:Triglycerides; D052216:Glucagon-Like Peptide 1; D002784:Cholesterol