GLP-1 and Extra-islet Effects

The main target of action of glucagon-like peptide-1 (GLP-1) is the islet, where the hormone stimulates insulin secretion, promotes beta cell proliferation and neogenesis, and inhibits glucagon secretion. However, GLP-1 receptors are also expressed outside the islets, increasing the likelihood that GLP-1 also plays a role in other organs. These functions are mainly the inhibition of gastric emptying, gastric acid secretion and exocrine pancreatic secretion, indicating that the hormone acts as an enterogastrone--a hormone released from the distal portion of the small intestine that inhibits proximal gastrointestinal events. Another important action of GLP-1 is to induce satiety. Other effects of the hormone include cardioprotection, neuroprotection, induction of learning and memory, stimulation of afferent, sensory nerves, stimulation of surfactant production in the lung, dilatation of pulmonary vessels, induction of diuresis, and also under some conditions, induction of antidiabetic actions unrelated to islet function. Thus, GLP-1 clearly has several manifestations of activity. The physiological relevance of these actions and their contribution to the overall antidiabetic action of GLP-1 when used in treatment of type 2 diabetes remains to be established.

[1]  K. Mensah,et al.  GLP-1 protects ischemic and reperfused myocardium via PI3kinase and p42/p44 MAPK signalling pathways , 2004 .

[2]  R. Roman,et al.  Antihypertensive effect of glucagon-like peptide 1 in Dahl salt-sensitive rats , 2003, Journal of hypertension.

[3]  D. Drucker,et al.  Cardiac function in mice lacking the glucagon-like peptide-1 receptor. , 2003, Endocrinology.

[4]  A. Cherrington,et al.  Effect of intraportal glucagon-like peptide-1 on glucose metabolism in conscious dogs. , 2003, American journal of physiology. Endocrinology and metabolism.

[5]  J. Egan,et al.  Glucagon-like peptide-1 augments insulin-mediated glucose uptake in the obese state. , 2002, The Journal of clinical endocrinology and metabolism.

[6]  C. Saper,et al.  Glucagon-like peptide-1 receptor stimulation increases blood pressure and heart rate and activates autonomic regulatory neurons. , 2002, The Journal of clinical investigation.

[7]  T. Welte,et al.  Vasorelaxant effect of glucagon-like peptide-(7-36)amide and amylin on the pulmonary circulation of the rat , 2001, Regulatory Peptides.

[8]  R. Pederson,et al.  Glucagon-like peptide-1 (7-37) augments insulin-mediated glucose uptake in elderly patients with diabetes. , 2001, The journals of gerontology. Series A, Biological sciences and medical sciences.

[9]  D. Drucker,et al.  Glucose competence of the hepatoportal vein sensor requires the presence of an activated glucagon-like peptide-1 receptor. , 2001, Diabetes.

[10]  A. Astrup,et al.  The effect of physiological levels of glucagon-like peptide-1 on appetite, gastric emptying, energy and substrate metabolism in obesity , 2001, International Journal of Obesity.

[11]  J. Balibrea,et al.  Glucagon-like peptide-1(7-36) amide stimulates surfactant secretion in human type II pneumocytes. , 2001, American journal of respiratory and critical care medicine.

[12]  Xia Li,et al.  Portal GLP-1 administration in rats augments the insulin response to glucose via neuronal mechanisms. , 2000, American journal of physiology. Regulatory, integrative and comparative physiology.

[13]  S. Rössner,et al.  Glucagon-like peptide 1 increases the period of postprandial satiety and slows gastric emptying in obese men. , 1998, The American journal of clinical nutrition.

[14]  E. Blázquez,et al.  Glucagon-like peptide-1-(7-36)amide increases pulmonary surfactant secretion through a cyclic adenosine 3',5'-monophosphate-dependent protein kinase mechanism in rat type II pneumocytes. , 1998, Endocrinology.

[15]  B. Yeğen,et al.  Glucagon-like peptide-1 inhibits gastric emptying via vagal afferent-mediated central mechanisms. , 1997, American journal of physiology. Gastrointestinal and liver physiology.

[16]  J. Holst,et al.  Glucagon-like peptide-1 reduces hepatic glucose production indirectly through insulin and glucagon in humans. , 1997, Acta physiologica Scandinavica.

[17]  E. Blázquez,et al.  Interactions of exendin-(9–39) with the effects of glucagon-like peptide-1-(7–36) amide and of exendin-4 on arterial blood pressure and heart rate in rats , 1996, Regulatory Peptides.

[18]  J. Holst,et al.  The Effect of Glucagon-Like Peptide I (GLP-I) on Glucose Elimination in Healthy Subjects Depends on the Pancreatic Glucoregulatory Hormones , 1996, Diabetes.

[19]  S. Kahn,et al.  Glucagon-like peptide 1 enhances glucose tolerance both by stimulation of insulin release and by increasing insulin-independent glucose disposal. , 1994, The Journal of clinical investigation.

[20]  E. Blázquez,et al.  Changes in arterial blood pressure and heart rate induced by glucagon-like peptide-1-(7-36) amide in rats. , 1994, The American journal of physiology.