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1
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A new metabolomic signature in type-2 diabetes mellitus and its pathophysiology
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1 Padberg, I., Peter, E., González-Maldonado, S., Witt, H., Mueller, M., Weis, T., et al. A new metabolomic signature in type-2 diabetes mellitus and its pathophysiology. PLoS ONE, 9, 2014, e85082.
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2
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Regulation of insulin synthesis and secretion and pancreatic beta-cell dysfunction in diabetes
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2 Fu, Z., Gilbert, E.R., Liu, D., Regulation of insulin synthesis and secretion and pancreatic beta-cell dysfunction in diabetes. Curr Diabet Rev, 9, 2013, 25.
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G protein-coupled receptors: signalling and regulation by lipid agonists for improved glucose homeostasis
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This review describes the recent advances in preclinical diabetes research of various fatty acid GPCRs involved in glucose homeostasis.
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3• Moran, B.M., Flatt, P.R., McKillop, A.M., G protein-coupled receptors: signalling and regulation by lipid agonists for improved glucose homeostasis. Acta Diabetol 53 (2016), 7–12 This review describes the recent advances in preclinical diabetes research of various fatty acid GPCRs involved in glucose homeostasis.
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Moran, B.M.1
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4 Ahren, B., Islet G protein-coupled receptors as potential targets for treatment of type 2 diabetes. Nat Rev Drug Discov 8 (2009), 369–385.
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This review demonstrates the therapeutic potential of incretin hormones, oxyntomodulin, cholecystokinin and the uses of combination therapies including double or triple agonist peptides.
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5• Irwin, N., Flatt, P.R., New perspectives on exploitation of incretin peptides for the treatment of diabetes and related disorders. World J Diabetes 10 (2015), 1285–1295 This review demonstrates the therapeutic potential of incretin hormones, oxyntomodulin, cholecystokinin and the uses of combination therapies including double or triple agonist peptides.
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Irwin, N.1
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6 Sheikh, A., Direct cardiovascular effects of glucagon like peptide-1. Diabetol Metab Syndr 5 (2013), 1–13.
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7 Zhao, T.C., Glucagon-like peptide-1 (GLP-1) and protective effects in cardiovascular disease: a new therapeutic approach for myocardial protection. Cardiovasc Diabetol 12 (2013), 1–8.
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10
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84975815650
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Evaluation of efficacy and safety of the glucagon receptor antagonist LY2409021 in patients with type 2 diabetes: 12- and 24-week phase 2 studies
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10 Kazda, C.M., Ding, Y., Kelly, R.P., Garhyan, P., Shi, C., Lim, C.N., et al. Evaluation of efficacy and safety of the glucagon receptor antagonist LY2409021 in patients with type 2 diabetes: 12- and 24-week phase 2 studies. Diabetes Care 39 (2016), 1241–1249.
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Kazda, C.M.1
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11
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Inhibitory effect of somatostatin on insulin secretion is not mediated via the CNS
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11 Hauge-Evans, A.C., Bowe, J., Franlin, Z.J., Hassan, Z., Jones, P.M., Inhibitory effect of somatostatin on insulin secretion is not mediated via the CNS. J Endocrinol 225 (2015), 19–26.
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Hauge-Evans, A.C.1
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12
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84901191678
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GPR120 (FFAR4) is preferentially expressed in pancreatic delta cells and regulates somatostatin secretion from murine islets of Langerhans
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This study establishes a role for GPR120 agonists in glucose stimulated somatostatin secretion and confirmed GPR120 expression on islet delta cells. Additionally, the response of the GPR120 was eliminated in GPR120 knockout mice.
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12• Stone, V.M., Dhayal, S., Brocklehurst, K.J., Lenaghan, C., Sorhede Winzell, M., Hammar, M., et al. GPR120 (FFAR4) is preferentially expressed in pancreatic delta cells and regulates somatostatin secretion from murine islets of Langerhans. Diabetologia 57 (2014), 1182–1191 This study establishes a role for GPR120 agonists in glucose stimulated somatostatin secretion and confirmed GPR120 expression on islet delta cells. Additionally, the response of the GPR120 was eliminated in GPR120 knockout mice.
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Stone, V.M.1
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13
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Pancreatic polypeptide regulates glucagon release in mouse and human alpha-cells
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13 Aragon, F., Karaca, M., Novials, A., Maldonado, R., Maechler, P., Rubi, B., Pancreatic polypeptide regulates glucagon release in mouse and human alpha-cells. Biochim Biophys Acta 1850 (2015), 343–351.
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Aragon, F.1
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14
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Cholecystokinin expression in the β-cell leads to increase β-cell area in aged mice and protects from streptozotocin-induced diabetes and apoptosis
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14 Lavine, J.A., Kibbe, C.R., Baan, M., Sirinvaravong, S., Umhoefer, H.M., Engler, K.A., et al. Cholecystokinin expression in the β-cell leads to increase β-cell area in aged mice and protects from streptozotocin-induced diabetes and apoptosis. Am J Physiol Endocrinol Metab 309 (2015), 819–828.
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Lavine, J.A.1
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15
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The effect of bariatric surgery on gastrointestinal and pancreatic hormones
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15 Meek, C.L., Lewis, H.B., Reimann, F., Gribble, F.M., Park, A.J., The effect of bariatric surgery on gastrointestinal and pancreatic hormones. Peptides 77 (2016), 28–37.
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16
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The role of peptide YY in gastrointestinal diseases and disorders
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16 El-Salhy, M., Mazzawi, T., Gundersen, D., Hatlebakk, J.G., Hausken, T., The role of peptide YY in gastrointestinal diseases and disorders. Int J Mol Med 31 (2013), 275–282.
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17 Pocai, A., Action and therapeutic potential of oxyntomodulin. Mol Metab 3 (2014), 241–251.
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The future role of gut hormones in the treatment of obesity
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This paper outlines the favourable effects of bariatric surgery on gut hormones including GLP-1, PYY, oxyntomodulin and PP.
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18• Troke, R.C., Tan, T.M., Bloom, S.R., The future role of gut hormones in the treatment of obesity. Ther Adv Chronic Dis 5 (2014), 4–14 This paper outlines the favourable effects of bariatric surgery on gut hormones including GLP-1, PYY, oxyntomodulin and PP.
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Troke, R.C.1
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19 Dezaki, K., Ghrelin function in insulin release and glucose metabolism. Endocr Dev 25 (2013), 135–143.
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20 Ulven, T., Short-chain free fatty acid receptors FFA2/GPR43 and FFA3/GPR41 as new potential therapeutic targets. Front Endocinol, 3, 2012, 111.
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Ulven, T.1
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21 Blad, C.C., Tang, C., Offermanns, S., G protein-coupled receptors for energy metabolites as new therapeutic targets. Nat Rev Drug Discov 11 (2012), 603–619.
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Blad, C.C.1
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22
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Medium-chain fatty acid-sensing receptor, GPR84, is a proinflammatory receptor
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22 Suzuki, M., Takaishi, S., Nagasaki, M., Onozawa, Y., Iino, I., Maeda, H., et al. Medium-chain fatty acid-sensing receptor, GPR84, is a proinflammatory receptor. J Biol Chem 288 (2013), 10684–10691.
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23
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23 Ferdaoussi, M., Bergeron, V., Kebede, M., Mancini, A., Alquier, T., Poitout, V., Free fatty acid receptor 1: a new drug target for type 2 diabetes?. Can J Diabetes 36 (2012), 275–280.
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24
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Activation of GPR40 a therapeutic target for the treatment of type 2 diabetes
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24 Burant, C.F., Activation of GPR40 a therapeutic target for the treatment of type 2 diabetes. Diabetes Care 36 (2013), 175–179.
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25 Defossa, E., Wagner, M., Recent developments in the discovery of FFA1 receptor agonists as novel oral treatment for type 2 diabetes mellitus. Bioorg Med Chem Lett 24 (2014), 2991–3000.
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Defossa, E.1
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26 Moran, B.M., Abdel-Wahab, Y.H., Flatt, P.R., McKillop, A.M., Evaluation of the insulin-releasing and glucose-lowering effects of GPR120 activation in pancreatic β-cells. Diabetes Obes Metab 16 (2014), 1128–1139.
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Moran, B.M.1
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27
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Activity of dietary fatty acids on FFA1 and FFA4 and characterisation of pinolenic acid as a dual FFA1/FFA4 agonist with potential effect against metabolic diseases
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27 Christiansen, E., Watterson, K.R., Stocker, C.J., Sokol, E., Jenkins, L., Simon, K., et al. Activity of dietary fatty acids on FFA1 and FFA4 and characterisation of pinolenic acid as a dual FFA1/FFA4 agonist with potential effect against metabolic diseases. Br J Nutr 113 (2015), 1677–1688.
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A potential role for GPR55 in the regulation of energy homeostasis
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28 Simcocks, A.C., O'Keefe, L., Jenkin, K.A., Mathai, M.L., Hryciw, D.H., McAinch, A.J., A potential role for GPR55 in the regulation of energy homeostasis. Drug Discov Today 24 (2013), 1–7.
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29 McKillop, A.M., Moran, B.M., Abdel-Wahab, Y.H.A., Flatt, P.R., Evaluation of insulin releasing and antihyperglycaemic activities of GPR55 lipid agonists using clonal beta-cells, isolated pancreatic islets and mice. Br J Pharmacol 170 (2013), 978–990.
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30 Moran, B.M., Abdel-Wahab, Y.H., Vasu, S., Flatt, P.R., McKillop, A.M., GPR39 receptors and actions of trace metals on pancreatic beta cell function and glucose homeostasis. Acta Diabetol 53 (2016), 279–293.
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31
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31 Meadows, A., Lee, J.H., Wu, C.S., Wei, Q., Pradhan, G., Yafi, M., et al. Deletion of G-protein-coupled receptor 55 promotes obesity by reducing physical activity. Int J Obes 40 (2016), 417–424.
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32 Odori, S., Hosoda, K., Tomita, T., Fujikura, J., Kusakabe, T., Kawaguchi, Y., et al. GPR119 expression in normal human tissues and islet cell tumors: evidence for its islet-gastrointestinal distribution, expression in pancreatic beta cell and alpha cells, and involvement in islet function. Metabolism 62 (2013), 70–78.
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33
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Activation of GPR119 by fatty acid agonists augments insulin release from clonal β-cells and isolated pancreatic islets and improves glucose tolerance in mice
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33 Moran, B.M., Abdel-Wahab, Y.H., Flatt, P.R., McKillop, A.M., Activation of GPR119 by fatty acid agonists augments insulin release from clonal β-cells and isolated pancreatic islets and improves glucose tolerance in mice. Biol Chem 395 (2014), 453–464.
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34
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GPR119 agonist AS1269574 activates TRPA1 cation channels to stimulate GLP-1 secretion
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2+ through transient receptor potential ankyrin 1 (TRPA1) cation channel. However, this mechanism was not identified with other GPR119 agonists including AR-231453 or oleoylethanolamide.
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2+ through transient receptor potential ankyrin 1 (TRPA1) cation channel. However, this mechanism was not identified with other GPR119 agonists including AR-231453 or oleoylethanolamide.
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35 Ezcurra, M., Reimann, F., Gribble, F.M., Emery, E., Molecular mechanisms of incretin hormone secretion. Curr Opin Pharmacol 13 (2013), 922–927.
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36 Reimann, F., Gribble, F.M., G protein-coupled receptors as a new therapeutic targets for type 2 diabetes. Diabetologia 59 (2016), 229–233.
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37 Scheen, A.J., Dulaglutide (LY-2189265) for the treatment of type 2 diabetes. Expert Rev Clin Pharmacol 9 (2016), 385–399.
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This study assessed the GLP-1-gastrin dual agonist ZP3022 in ZDF rats. ZP3022 improved glucose tolerance and increased insulin release following an OGTT and increased islet beta cell mass.
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38• Skarbaliene, J., Secher, T., Jelsing, J., Ansarullah, Neerup, T.S., Billestrup, N., et al. The anti-diabetic effects of GLP-1-gastrin dual agonist ZP3022 in ZDF rats. Peptides 69 (2015), 47–55 This study assessed the GLP-1-gastrin dual agonist ZP3022 in ZDF rats. ZP3022 improved glucose tolerance and increased insulin release following an OGTT and increased islet beta cell mass.
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39 Butsch, W.S., Obesity medications: what does the future look like?. Curr Opin Endocrinol Diabetes Obes 22 (2015), 360–366.
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40 Nuffer, W., Trujillo, J.M., Megyeri, J., A comparison of new pharmacological agents for the treatment of obesity. Ann Pharmacother 50 (2016), 376–388.
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41 Gale, E.A., GLP-1 based agents and acute pancreatitis: drug safety falls victim to the three monkey paradigm. BMJ, 346, 2013, f1263.
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42 Azoulay, L., Filion, K.B., Platt, R.W., Dahl, M., Dormuth, C.R., Clemens, K.K., et al. Incretin based drugs and the risk of pancreatic cancer: international multicentre cohort study. BMJ, 352, 2016, i581.
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A novel glucagon-like peptide-1 (GLP-1)/glucagon hybrid peptide with triple-acting agonist activity at glucose-dependent insulinotropic polypeptide, GLP-1, and glucagon receptors and therapeutic potential in high fat-fed mice
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43 Gault, V.A., Bhat, V.K., Irwin, N., Flatt, P.R., A novel glucagon-like peptide-1 (GLP-1)/glucagon hybrid peptide with triple-acting agonist activity at glucose-dependent insulinotropic polypeptide, GLP-1, and glucagon receptors and therapeutic potential in high fat-fed mice. J Biol Chem 288 (2013), 35581–35591.
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44 Finan, B., Ma, T., Ottaway, N., Muller, T.D., Habegger, K.M., Heppner, K.M., et al. Unimolecular dual incretins maximize metabolic benefits in rodents, monkeys and humans. Sci Transl Med, 5, 2013, 209.
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This study demonstrated a triple agonist against glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon receptors which reduced body weight and diabetic complications in rodent models of obesity.
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45•• Finan, B., Yang, B., Ottaway, N., Smiley, D.L., Ma, T., Clemmensen, C., et al. A rationally designed monomeric peptide triagonist corrects obesity and diabetes in rodents. Nat Med 21 (2015), 27–36 This study demonstrated a triple agonist against glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon receptors which reduced body weight and diabetic complications in rodent models of obesity.
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Novel dual agonist peptide analogues derived from dogfish glucagon show promising in vitro insulin releasing actions and antihyperglycaemic activity in mice
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This study assessed the antidiabetic potential of thirteen novel dogfish glucagon derived analogues were assessed in vitro and in acute in vivo studies. The analogues enhanced glucose induced insulin secretion from BRIN-BD11 cells and improved glucose tolerance in high fat fed diabetic mice, GIP receptor knockout mice but not GLP-1 knockout mice.
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46• O'Harte, F.P.M., Ng, M.T., Lynch, A.M., Conlon, J.M., Flatt, P.R., Novel dual agonist peptide analogues derived from dogfish glucagon show promising in vitro insulin releasing actions and antihyperglycaemic activity in mice. Mol Cell Endocrinol 431 (2016), 133–144 This study assessed the antidiabetic potential of thirteen novel dogfish glucagon derived analogues were assessed in vitro and in acute in vivo studies. The analogues enhanced glucose induced insulin secretion from BRIN-BD11 cells and improved glucose tolerance in high fat fed diabetic mice, GIP receptor knockout mice but not GLP-1 knockout mice.
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Dogfish glucagon analogues counter hyperglycaemia and enhance both insulin secretion and action in diet-induced obese diabetic mice
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Chronic use of selected dogfish glucagon analogues (dual GLP-1 and glucagon receptor agonists) in diet induced high fat fed mice decreased non-fasting blood glucose and improved i.p. and oral glucose tolerance with concomitant increased insulin as well as significantly reducing plasma triglycerides concentrations and decreasing pancreatic glucagon content.
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47•• O'Harte, F.P.M., Ng, M.T., Lynch, A.M., Conlon, J.M., Flatt, P.R., Dogfish glucagon analogues counter hyperglycaemia and enhance both insulin secretion and action in diet-induced obese diabetic mice. Diabetes Obes Metab, 2016, 18, 10.1111/dom.12713 Chronic use of selected dogfish glucagon analogues (dual GLP-1 and glucagon receptor agonists) in diet induced high fat fed mice decreased non-fasting blood glucose and improved i.p. and oral glucose tolerance with concomitant increased insulin as well as significantly reducing plasma triglycerides concentrations and decreasing pancreatic glucagon content.
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Diabetes Obes Metab
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The novel GLP-1-gastrin dual agonist, ZP3022, increases β-cell mass and prevents diabetes in db/db mice
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48 Fosgerau, K., Jessen, L., Lind Tolborg, J., Osterlund, T., Schaeffer Larsen, K., Rolsted, K., et al. The novel GLP-1-gastrin dual agonist, ZP3022, increases β-cell mass and prevents diabetes in db/db mice. Diabetes Obes Metab 15 (2013), 62–71.
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Diabetes and obesity treatment based on dual incretin receptor activation – “twincretins”
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[Epub ahead of print] This review discusses the recent advances and challenges facing GLP-1R, GIPR dual agonists in preclinical and clinical trials.
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49• Skow, M.A., Bergmann, N.C., Knop, F.K., Diabetes and obesity treatment based on dual incretin receptor activation – “twincretins”. Diabetes Obes Metab, 2016 [Epub ahead of print] This review discusses the recent advances and challenges facing GLP-1R, GIPR dual agonists in preclinical and clinical trials.
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Peptide therapeutics: current status and future directions
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This review covers peptide therapeutics and discusses commercial aspects covering emerging peptide technologies and cell-penetrating peptides. It covers multifunctional peptides and peptide drug conjugates and the enormous growth potential of peptides in future therapeutics.
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50•• Fosgerau, K., Hoffmann, T., Peptide therapeutics: current status and future directions. Drug Discov Today 20 (2015), 122–128 This review covers peptide therapeutics and discusses commercial aspects covering emerging peptide technologies and cell-penetrating peptides. It covers multifunctional peptides and peptide drug conjugates and the enormous growth potential of peptides in future therapeutics.
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52 Li, X., Zhong, K., Guo, Z., Zhong, D., Chen, X., Fasiglifam (TAK-875) inhibits hepatobiliary transporters: a possible factor contributing to fasiglifam-induced liver injury. Drug Metab Dispos 43 (2015), 1751–1759.
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Evaluation of drug interactions of GSK1292263 (a GPR119 agonist) with statins: from in vitro data to clinical study design
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53 Polli, J.W., Hussey, E., Bush, M., Generaux, G., Smith, G., Collins, D., et al. Evaluation of drug interactions of GSK1292263 (a GPR119 agonist) with statins: from in vitro data to clinical study design. Xenobiotica 43 (2013), 498–508.
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