TITLE

Liraglutide, a GLP-1 Analog, Stimulates both Exocytosis and Mobilization of Insulin Granules

AUTHOR(S)
Ma, Li; Labno, Christine; Kuznetsov, Andrey; Bindokas, Vytautas P.; Philipson, Louis H.
PUB. DATE
June 2007
SOURCE
Diabetes;Jun2007 Supplement 1, Vol. 56, pA436
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
GLP-1 increases cAMP and stimulates insulin granule exocytosis but the effects on insulin granule dynamics are incompletely understood. We used total internal reflection fluorescence (TIRF) microscopy to image the exocytosis and transport of GFP-insulin granules near the plasma membrane in stable transfected glucose-responsive MIN6 insulinoma cells. We found that the long-acting GLP-1 analog liraglutide evoked insulin granule exocytosis in a biphasic manner. In the first five minutes after stimulation (first phase of release) fusion events were seen mostly from previously docked granules. In low (2 mM/L) glucose there were few exocytotic events (loss of granules < 2% of total visualized granules) unchanged with or without liraglutide. In 5 mM/L glucose, there was only a slight increase in insulin granule exocytosis with liraglutide compared with controls (4.0 ± 0.82% to 3.3 ± 0.87%, P > 0.05). However, in 8 mM/L glucose, there was almost a doubling in the disappearance of docked insulin granules with liraglutide than without it (8.6 ± 0.93% to 4.6 ± 1.3%, P < 0.01). To isolate the effect of liraglutide on internal granule trafficking to the plasma membrane, previously docked granules (PDG) were first photo-bleached using TIRF (TIRF-FRAP) and the appearance of newly docked granules (NDG) at the plasma membrane over the next 5-20 minutes was recorded. In the presence of liraglutide, there was an increase in the rate of appearance NDG, as expressed as percentage of total PDG (2.37 ± 0.496 per min. compared to 1.52 ± 0.301 per min. for controls, P < 0.01). These findings indicate that liraglutide increases insulin granule exocytosis from the pre-docked pool and leads to the mobilization of more insulin secretory granules from the large reservoir pool to then dock at the plasma membrane. Both of these processes are glucose dependent. This method of using TIRF and TIRF-FRAP approach can therefore evaluate both exocytosis of docked insulin granules as well as transport of insulin granules to the plasma membrane.
ACCESSION #
25822013

 

Related Articles

  • Gluco-incretins control insulin secretion at multiple levels as revealed in mice lacking GLP-1 and GIP receptors. Preitner, Frédéric; Ibberson, Mark; Franklin, Isobel; Binnert, Christophe; Pende, Mario; Gjinovci, Asllan; Hansotia, Tanya; Drucker, Daniel J.; Wollheim, Claes; Burcelin, Rémy; Thorens, Bernard // Journal of Clinical Investigation;Feb2004, Vol. 113 Issue 4, p635 

    The role of the gluco-incretin hormones GIP and GLP-1 in the control of b cell function was studied by analyzing mice with inactivation of each of these hormone receptor genes, or both. Our results demonstrate that glucose intolerance was additively increased during oral glucose absorption when...

  • No Hypoglycemia After Subcutaneous Administration of Glucagon-Like Peptide-1 in Lean Type 2 Diabetic Patients and in Paients With Diabetes Secondary to Chronic Pancreatits. Knop, Filip K.; Vilsb∅ll, Tina; Larsen, Steen; Madsbad, Sten; Holst, Jens J.; Krarup, Thure // Diabetes Care;Sep2003, Vol. 26 Issue 9, p2581 

    OBJECTIVE — Glucagon-like peptide 1 (GLP-1) is a proglucagon derivative secreted primarily from the L-cells of the small intestinal mucosa in response to the ingestion of meals. GLP-1 stimulates insulin secretion and inhibits glucagon secretion. It has previously been shown that...

  • Correction.  // Experimental Diabetes Research;2011, Special section p1 

    A correction to the article "Subthreshold α2-Adrenergic Activation Counteracts Glucagon-Like Peptide-1 Potentiation of Glucose-Stimulated Insulin Secretion" that was published in a January 2011 issue is presented.

  • The Influence of GLP-1 on Glucose-Stimulated Insulin Secretion. Kjems, Lise L.; Holst, Jens J.; Vølund, Aage; Madsbad, Sten // Diabetes;Feb2003, Vol. 52 Issue 2, p380 

    The intestinally derived hormone glucagon-like peptide 1 (GLP-1) (7-36 amide) has potent effects on glucosemediated insulin secretion, insulin gene expression, and p-cell growth and differentiation. It is, therefore, considered a potential therapeutic agent for the treatment of type 2 diabetes....

  • Subthreshold α2-Adrenergic Activation Counteracts Glucagon-Like Peptide-1 Potentiation of Glucose-Stimulated Insulin Secretion. Minglin Pan; Guang Yang; Xiuli Cui; Shao-Nian Yang // Experimental Diabetes Research;2011, Special section p1 

    The pancreatic β cell harbors α2-adrenergic and glucagon-like peptide-1 (GLP-1) receptors on its plasma membrane to sense the corresponding ligands adrenaline/noradrenaline and GLP-1 to govern glucose-stimulated insulin secretion. However, it is not known whether these two signaling...

  • On the Horizon. Karl, Elka // Diabetes Health;Oct2004, Vol. 13 Issue 10, p74 

    Presents a study on the effect of the combination of glucagon-like peptide (GLP-1) and Actos or pioglitazone on blood glucose levels. Treatments used in the study; Effect of GLP-1 monotherapy on insulin levels; Conclusion of the study.

  • Glucagon-Like Peptide 1 increases insulin sensitivity in depancreatized dogs. Sandhu, Harmanjit; Wiesenthal, Stephanie R.; MacDonald, Patrick E.; McCall, Richard H.; Tchipashvili, Vaja; Rashid, Shirya; Satkunarajah, Malathy; Irwin, David M.; Z. Qing Shi; Brubaker, Patricia L.; Wheeler, Michael B.; Vranic, Mladen; Efendic, Suad; Giacca, Adria // Diabetes;May99, Vol. 48 Issue 5, p1045 

    Determines the function of glucagon-like peptide 1 (GLP-1) on insulin sensitivity and secretion in depancreatized dogs. Differences in insulin-induced suppression of glucose production in GLP-1 and saline; Effect of GLP-1 on plasma glucose and insulin levels; Role of GLP-1 on insulin action...

  • Engineering physiologically regulated insulin secretion in non-ß cells by expressing glucagon-like peptide 1 receptor. Wu, L.; Nicholson, W.; Wu, C.-Y.; Xu, M.; McGaha, A.; Shiota, M.; Powers, A.C. // Gene Therapy;Sep2003, Vol. 10 Issue 19, p1712 

    Glucagon-like peptide 1 (GLP-1) is released from neuroendocrine cells in the intestine in the postprandial state and augments glucose-stimulated insulin secretion from pancreatic ß cells. To develop non-ß cells that exhibit physiologically regulated insulin secretion, we coexpressed the...

  • The Possible Protective Role of Glucagon-Like Peptide 1 on Endothelium During the Meal and Evidence for an "Endothelial Resistance" to Glucagon-Like Peptide 1 in Diabetes. CERIELLO, ANTONIO; ESPOSITO, KATHERINE; TESTA, ROBERTO; BONFIGLI, ANNA RITA; MARRA, MAURIZIO; GIUGLIANO, DARIO // Diabetes Care;Mar2011, Vol. 34 Issue 3, p697 

    OBJECTIVE--Glucagon-like peptide 1 (GLP-1) stimulates insulin secretion. However, GLP-1 also improves endothelial function in diabetes. RESEARCH DESIGN AND METHODS--Sixteen type 2 diabetic patients and 12 control subjects received a meal, an oral glucose tolerance test (OGTT), and two...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics