Glucagon-like-peptide

As indicated earlier, most cases of type 1 diabetes are caused by an autoimmune response that selectively attacks and destroys pancreatic beta cells in susceptible individuals. Therefore, drugs that suppress this autoimmune response may be helpful in limiting beta cell destruction, thereby decreasing the severity of this disease.4,41 Several immunosuppressants have been investigated as a way to potentially minimize beta cell loss from the autoimmune reactions underlying type 1 diabetes some immunosuppressants that have been considered for this situation include cyclosporine, azathioprine, cyclophosphamide, methotrexate, and glucocorticoids.11 The pharmacology of these immunosuppressants is discussed in more detail in Chapter 37. 

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Appetite-suppressing. Neuropqrtide modulators and gut hormones with anorexigenic effects are a-melanocortin-stimulating hormone (a-MSH), cocaine- and amphetamine-regulated transcript (CART), glucagon-like peptide-1 (GLP-1), leptin, insulin, oxyntomodulin, pancreatic peptide PP, peptide YY and PYY3 36, and others. 

Antidiabetic Drugs other than Insulin. Table 3 Actions of the incretin hormones GIP (glucose-dependent insulinotropic polypeptide, gastric inhibitory peptide) and GLP-1 (glucagon-like peptide-1)... 

Holst JJ (2006) Glucagon-like peptide-1 from extract to agent Diabetologia 49 253-260... 

Incretins gut hormones that increase glucose-stimulated insulin secretion GLP-1 glucagon-like peptide-1 GDP Gastric inhibitory peptide or glucose-dependent insulino-tropic peptide... 

Thorens B, Waeber G (1993) Glucagon-like peptide-I and the control of insulin secretion in the normal state and in NIDDM. Diabetes 42 1219-1225... 

Another interesting target for this type of inhibitors is the dipeptidyl peptidase IV (DPP IV). This exodipeptidase, which can cleave peptides behind a proline residue is important in type 2 diabetes as it truncates the glucagon-like peptide 1. Taking into account the P2-Pi( Pro)-P,1 cleavage and the requirement for a free terminal amine, the synthesis of a suicide inhibitor was planned. It looked as if the the e-amino group of a P2 lysine residue could be cyclized because of the relative little importance of the nature of the P2 residue on the rate of enzymatic hydrolysis of known synthetic substrates. Therefore, anew series of cyclopeptides 11 was synthesized (Fig. 11.8). 

Acuna-Goycolea C., van den Pol A (2004). Glucagon-like peptide 1 excites... 

Gutniak, M.K., Svartberg, J., Hellstrom, P.M. et al. (2001) Antidiabetogenic action of glucagon-like peptide-1 related to administration relative to meal intake in subjects with type 2 diabetes. Journal of Internal Medicine, 250, 81-87. 

Lee, D.-H., Kim, S.-G., Park, Y.-C. et al. (2007) Proteome analysis of recombinant Escherichia coli producing human glucagon-like peptide-1. Analytical Tools for Proteomics, 849, 323-330. 

Drucker, D. 2002. Biological actions and therapeutic potential of the glucagon-like peptides. Gastroenterology 122(2), 531-544. 

Gordienko D V, Bolton TB, Cannell MB 1998 Variability in spontaneous subcellular Ca2+ release in guinea-pig ileum smooth muscle cells. J Physiol 507 707-720 Ho R, Shao Z 1991 Axial resolution of confocal microscopes revisited. Optiik 88 147—154 Holz GG, Leech CA, Heller RS, Castonguay N, Habener JF 1999 cAMP-dependent mobilization of intracellular Ca2+ stores by activation of ryanodine receptors in pancreatic [j cells. A Ca2+ signaling system stimulated by the insulinotropic hormone glucagon-like peptide-1-(7-37). J Biol Chem 274 14147-14156 Lipsius SL, Hiiser J, Blatter LA 2001 Intracellular Ca2+ release sparks atrial pacemaker activity. News Physiol Sci 16 101-106... 

R. P. Pauly, F. Rosche, M. Wermann, C. H. McIntosh, R. A. Pederson, and H. U. Demuth. Investigation of Glucose-Dependent Insulinotropic Polypeptide-(l-42) and Glucagon-like Peptide-1-(7-36) Degradation In Vitro by Dipeptidyl Peptidase IV Using Matrix-Assisted... 

Madsen, J.L. and Holst, J.J. (2002) Effect of 6-week course of glucagon-like peptide... 

Glucagon-like peptide 1 abasis of a new class of treatment for type 2 diabetes. Journal of Medicinal Chemistry, 47, 4128 134 (b) Vahl, T.P. and D Alessio, D.A. (2004) Gut peptides in the treatment of diabetes mellitus. Expert Opinion on Investigational Drugs, 13, 177-188 (c) Meier, J.J. and Nauck, M.A. 

Glucagon-like peptide 1 (GLP-1) in biology and pathology. Diabetes/ Metabolism Research and Reviews, 21, 91-117 (d) Drucker, D.J. and Nauck, M. 

Flint, A., Raben, A., Ersboll, A.K., Holst, J.J. and Astrup, A. (2001) The effect of physiological levels of glucagons-like peptide-1 on appetite, gastric emptying, energy and substrate metabolism in obesity. International Journal of Obesity, 25, 781-792. 

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