Alpha cells come of age

Trends in Endocrinology and Metabolism

Volumn 24, Issue 3, 2013, Pages 153-163

  Habener, Joel F ^a   Stanojevic, Violeta ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

Alpha cell hyperplasia; Beta cell regeneration; GLP 1 derived peptides; Transdifferentiation

Indexed keywords

ANTIOXIDANT; ANTISENSE OLIGONUCLEOTIDE; CYCLIC AMP; CYCLIN D1; GASTROINTESTINAL HORMONE; GHRELIN; GLUCAGON; GLUCAGON LIKE PEPTIDE 1; GLUCAGON LIKE PEPTIDE 2; GLUCAGON LIKE PEPTIDE 2 RECEPTOR AGONIST; GUANINE NUCLEOTIDE BINDING PROTEIN; INSULIN; NEUROGENIN 3; PROPROTEIN CONVERTASE 1; RECEPTOR ANTIBODY; SOMATOSTATIN; STREPTOZOCIN; TRANSCRIPTION FACTOR PAX4; TRANSCRIPTION FACTOR PDX 1; TRANSCRIPTION FACTOR SOX9; UNCLASSIFIED DRUG;

CARBOXY TERMINAL SEQUENCE; CELL AGING; CELL COMMUNICATION; CELL CYCLE; CELL DAMAGE; CELL DEDIFFERENTIATION; CELL DIFFERENTIATION; CELL GROWTH; CELL HYPERPLASIA; CELL LINE; CELL LINEAGE; CELL REGENERATION; CELL SURVIVAL; CONFOCAL MICROSCOPY; EMBRYONIC STEM CELL; ENDOCRINE CELL; ENTERITIS; EPITHELIAL MESENCHYMAL TRANSITION; GENE EXPRESSION; GENE OVEREXPRESSION; GENE SILENCING; HEART FAILURE; HOMEOSTASIS; HYPERGLYCEMIA; IMMUNE DEFICIENCY; INSULIN DEPENDENT DIABETES MELLITUS; INSULIN LIKE ACTIVITY; MESENCHYMAL STEM CELL; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PANCREAS ISLET ALPHA CELL; PANCREAS ISLET BETA CELL; PARACRINE SIGNALING; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN STRUCTURE; REVIEW; SIGNAL TRANSDUCTION; STEM CELL; TOPOGRAPHY;

ANIMALS; CELL DEDIFFERENTIATION; CELL LINEAGE; CELL TRANSDIFFERENTIATION; DIABETES MELLITUS, EXPERIMENTAL; ENTEROENDOCRINE CELLS; EPITHELIAL-MESENCHYMAL TRANSITION; GLUCAGON; GLUCAGON-LIKE PEPTIDE 1; GLUCAGON-SECRETING CELLS; HOMEODOMAIN PROTEINS; HUMANS; HYPERPLASIA; INSULIN-SECRETING CELLS; ISLETS OF LANGERHANS; MICE; PAIRED BOX TRANSCRIPTION FACTORS; PROPROTEIN CONVERTASE 1; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTORS;

EID: 84875270169     PISSN: 10432760     EISSN: 18793061     Source Type: Journal    
DOI: 10.1016/j.tem.2012.10.009     Document Type: Review

References (138)

1. Thorel F., et al. Conversion of adult pancreatic alpha-cells to beta-cells after extreme beta-cell loss. Nature 2010, 464:1149-1154.
2. Chung C.H., et al. Pancreatic beta cell neogenesis by direct conversion from mature alpha cells. Stem Cells 2010, 28:1630-1638.
3. Collombat P., et al. The ectopic expression of Pax4 in the mouse pancreas converts progenitor cells into alpha and subsequently beta cells. Cell 2009, 138:449-462.
4. Yang Y.P., et al. Context-specific alpha- to-beta-cell reprogramming by forced Pdx1 expression. Genes Dev. 2011, 25:1680-1685.
5. Nie Y., et al. Regulation of pancreatic PC1 and PC2 associated with increased glucagon-like peptide 1 in diabetic rats. J. Clin. Invest. 2000, 105:955-965.
6. Thyssen S., et al. Ontogeny of regeneration of beta cells in the neonatal rat after treatment with streptozotocin. Endocrinology 2006, 147:2346-2356.
7. Hansen A.M., et al. Upregulation of alpha cell glucagon-like peptide 1 (GLP-1) in Psammomys obesus - an adaptive response to hyperglycaemia?. Diabetologia 2011, 54:1379-1387.
8. Liu Z., et al. Stromal cell-derived factor-1 (SDF-1)/chemokine (C-X-C motif) receptor 4 (CXCR4) axis activation induces intra-islet glucagon-like peptide-1 (GLP-1) production and enhances beta cell survival. Diabetologia 2011, 54:2067-2076.
9. Wideman R.D., et al. Improving function and survival of pancreatic islets by endogenous production of glucagon-like peptide 1. Proc. Natl. Acad. Sci. U.S.A. 2006, 103:13468-13473.
10. Kilimnik G., et al. Intraislet production of GLP-1 by activation of prohormone convertase 1/3 in pancreatic alpha-cells in mouse models of β-cell regeneration. Islets 2010, 2:149-155.
11. Whalley N.M., et al. Processing of proglucagon to GLP-1 in pancreatic alpha-cells: is this a paracrine mechanism enabling GLP-1 to act on beta cells?. J. Endocrinol. 2011, 211:99-106.
12. Zhang Y., et al. Regeneration of pancreatic non-beta endocrine cells in adult mice following a single diabetes-inducing dose of streptozotocin. PLoS ONE 2012, 7:e36675.
13. Willcox A., et al. Evidence of increased islet cell proliferation in patients with recent-onset type 1 diabetes. Diabetologia 2010, 53:2020-2028.
14. Gromada J., et al. Alpha cells of the endocrine pancreas: 35 years of research but the enigma remains. Endocrinol. Rev. 2007, 28:84-116.
15. Lamothe B., et al. Genetic engineering in mice: impact on insulin signalling and action. Biochem. J. 1998, 335:193-204.
16. Hancock A.S., et al. Glucagon deficiency reduces hepatic glucose production and improves glucose tolerance in adult mice. Mol. Endocrinol. 2010, 24:1605-1614.
17. Dunning B.E., Gerich J.E. The role of alpha-cell dysregulation in fasting and postprandial hyperglycemia in type 2 diabetes and therapeutic implications. Endocr. Rev. 2007, 28:253-283.
18. Unger R.H., Cherrington A.D. Glucagonocentric restructuring of diabetes: a pathophysiologic and therapeutic makeover. J. Clin. Invest. 2012, 122:4-12.
19. Webb G.C., et al. Glucagon replacement via micro-osmotic pump corrects hypoglycemia and alpha-cell hyperplasia in prohormone convertase 2 knockout mice. Diabetes 2002, 51:398-405.
20. Gelling R.W., et al. Lower blood glucose, hyperglucagonemia, and pancreatic alpha cell hyperplasia in glucagon receptor knockout mice. Proc. Natl. Acad. Sci. U.S.A. 2003, 100:1438-1443.
21. Sloop K.W., et al. Hepatic and glucagon-like peptide-1-mediated reversal of diabetes by glucagon receptor antisense oligonucleotide inhibitors. J. Clin. Invest. 2004, 113:1571-1581.
22. Chen M., et al. Increased glucose tolerance and reduced adiposity in the absence of fasting hypoglycemia in mice with liver-specific Gs alpha deficiency. J. Clin. Invest. 2005, 115:3217-3227.
23. Conarello S.L., et al. Glucagon receptor knockout mice are resistant to diet-induced obesity and streptozotocin-mediated beta cell loss and hyperglycaemia. Diabetologia 2007, 50:142-151.
24. Sørensen H., et al. Glucagon receptor knockout mice display increased insulin sensitivity and impaired beta-cell function. Diabetes 2006, 55:3463-3469.
25. Gu W., et al. Long-term inhibition of the glucagon receptor with a monoclonal antibody in mice causes sustained improvement in glycemic control, with reversible alpha-cell hyperplasia and hyperglucagonemia. J. Pharmacol. Exp. Ther. 2009, 331:871-881.
26. Lee Y., et al. Glucagon receptor knockout prevents insulin-deficient type 1 diabetes in mice. Diabetes 2011, 60:391-397.
27. Ali S., et al. Dual elimination of the glucagon and GLP-1 receptors in mice reveals plasticity in the incretin axis. J. Clin. Invest. 2011, 121:1917-1929.
28. Winzell M.S., et al. Glucagon receptor antagonism improves islet function in mice with insulin resistance induced by a high-fat diet. Diabetologia 2007, 50:1453-1462.
29. Hayashi Y., et al. Mice deficient for glucagon gene-derived peptides display normoglycemia and hyperplasia of islet α-cells but not of intestinal L-cells. Mol. Endocrinol. 2009, 23:1990-1999.
30. Brand C.L., et al. Immunoneutralization of endogenous glucagon with monoclonal glucagon antibody normalizes hyperglycaemia in moderately streptozotocin-diabetic rats. Diabetologia 1994, 37:985-993.
31. Parker J.C., et al. Glycemic control in mice with targeted disruption of the glucagon receptor gene. Biochem. Biophys. Res. Commun. 2002, 290:839-843.
32. Liang Y., et al. Reduction in glucagon receptor expression by an antisense oligonucleotide ameliorates diabetic syndrome in db/db mice. Diabetes 2004, 53:410-417.
33. Cabrera O., et al. The unique cytoarchitecture of human pancreatic islets has implications for islet cell function. Proc. Natl. Acad. Sci. U.S.A. 2006, 103:2334-2339.
34. Steiner D.J., et al. Pancreatic islet plasticity: interspecies comparison of islet architecture and composition. Islets 2010, 2:135-145.
35. Bosco D., et al. Unique arrangement of alpha- and beta-cells in human islets of Langerhans. Diabetes 2010, 59:1202-1210.
36. Unger R.H., Orci L. Paracrinology of islets and the paracrinopathy of diabetes. Proc. Natl. Acad. Sci. U.S.A. 2010, 107:16009-16012.
37. Kawamori D., et al. Insulin signaling in alpha cells modulates glucagon secretion in vivo. Cell Metab. 2009, 9:350-361.
38. Gelling R.W., et al. Pancreatic beta-cell overexpression of the glucagon receptor gene results in enhanced beta-cell function and mass. Am. J. Physiol. Endocrinol. Metab. 2009, 297:E695-E707.
39. Rezania A., et al. Production of functional glucagon-secreting alpha-cells from human embryonic stem cells. Diabetes 2011, 60:239-247.
40. Rezania A., et al. Maturation of human embryonic stem cell-derived pancreatic progenitors into functional islets capable of treating pre-existing diabetes in mice. Diabetes 2012, 61:2016-2029.
41. Liang X.D., et al. Streptozotocin-induced expression of Ngn3 and Pax4 in neonatal rat pancreatic alpha cells. World J. Gastroenterol. 2011, 17:2812-2820.
42. Chen S., et al. Transient overexpression of cyclin D2/CDK4/GLP1 genes induces proliferation and differentiation of adult pancreatic progenitors and mediates islet regeneration. Cell Cycle 2012, 11:695-705.
43. Yanger K., Stanger B.Z. Facultative stem cells in liver and pancreas: fact and fancy. Dev. Dyn. 2011, 240:521-529.
44. Dor Y., et al. Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation. Nature 2004, 429:41-46.
45. Nir T., et al. Recovery from diabetes in mice by beta cell regeneration. J. Clin. Invest. 2007, 117:2553-2561.
46. Cano D.A., et al. Regulated beta-cell regeneration in the adult mouse pancreas. Diabetes 2008, 57:958-966.
47. Teta M., et al. Growth and regeneration of adult beta cells does not involve specialized progenitors. Dev. Cell 2007, 12:817-826.
48. Xu X., et al. Beta cells can be generated from endogenous progenitors in injured adult mouse pancreas. Cell 2008, 132:197-207.
49. Inada A., et al. Carbonic anhydrase II-positive pancreatic cells are progenitors for both endocrine and exocrine pancreas after birth. Proc. Natl. Acad. Sci. U.S.A. 2008, 105:19915-19919.
50. Russ H.A., et al. Epithelial-mesenchymal transition in cells expanded in vitro from lineage-traced adult human pancreatic beta cells. PLoS ONE 2009, 4:e6417.
51. Russ H.A., et al. Insulin-producing cells generated from dedifferentiated human pancreatic beta cells expanded in vitro. PLoS ONE 2011, 6:e25566.
52. Seymour P.A., Sander M. Historical perspective: beginnings of the beta-cell: current perspectives in beta-cell development. Diabetes 2011, 60:364-376.
53. Jonsson J., et al. Insulin-promoter-factor 1 is required for pancreas development in mice. Nature 1994, 371:606-609.
54. Stoffers D.A., et al. Pancreatic agenesis attributable to a single nucleotide deletion in the human IPF1 gene coding sequence. Nat. Genet. 1997, 15:106-110.
55. Gradwohl G., et al. Neurogenin3 is required for the development of the four endocrine cell lineages of the pancreas. Proc. Natl. Acad. Sci. U.S.A. 2000, 97:1607-1611.
56. Apelqvist A., et al. Notch signalling controls pancreatic cell differentiation. Nature 1999, 400:877-881.
57. Collombat P., et al. Pancreatic beta-cells: from generation to regeneration. Semin. Cell Dev. Biol. 2010, 21:838-844.
58. Courtney M., et al. In vivo conversion of adult alpha cells into beta-like cells: a new research avenue in the context of type 1 diabetes. 20. Diabetes Obes. Metab. 2011, 13(Suppl. 1):47-52.
59. Sosa-Pineda B., et al. The Pax4 gene is essential for differentiation of insulin-producing beta cells in the mammalian pancreas. Nature 1997, 386:399-402.
60. Collombat P., et al. Embryonic endocrine pancreas and mature beta cells acquire alpha and PP cell phenotypes upon Arx misexpression. J. Clin. Invest. 2007, 117:961-970.
61. Dhawan S., et al. Pancreatic beta cell identity is maintained by DNA methylation-mediated repression of Arx. Dev. Cell 2011, 20:419-429.
62. Collombat P., et al. The simultaneous loss of Arx and Pax4 genes promotes a somatostatin-producing cell fate specification at the expense of the alpha- and beta-cell lineages in the mouse endocrine pancreas. Development 2005, 132:2969-2980.
63. Habener J.F. A perspective on pancreatic stem/progenitor cells. Pediatr. Diabetes 2004, 5(Suppl. 2):29-37.
64. Thiery J.P. Epithelial-mesenchymal transitions in development and pathologies. Curr. Opin. Cell Biol. 2003, 15:740-746.
65. Zulewski H., et al. Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiate ex vivo into pancreatic endocrine, exocrine, and hepatic phenotypes. Diabetes 2001, 50:521-533.
66. Gershengorn M.C., et al. Epithelial-to-mesenchymal transition generates proliferative human islet precursor cells. Science 2004, 306:2261-2264.
67. Efrat S., Russ H.A. Making beta cells from adult tissues. Trends Endocrinol. Metab. 2012, 23:278-285.
68. Lechner A., et al. Redifferentiation of insulin-secreting cells after in vitro expansion of adult human pancreatic islet tissue. Biochem. Biophys. Res. Commun. 2005, 327:581-588.
69. Nieto M.A. The snail superfamily of zinc-finger transcription factors. Nat. Rev. Mol. Cell Biol. 2002, 3:155-166.
70. Rukstalis J.M., et al. Transcription factor snail modulates hormone expression in established endocrine pancreatic cell lines. Endocrinology 2006, 147:2997-3006.
71. Rukstalis J.M., Habener J.F. Snail2, a mediator of epithelial-mesenchymal transitions, expressed in progenitor cells of the developing endocrine pancreas. Gene Expr. Patterns 2007, 7:471-479.
72. Talchai C., et al. Pancreatic β cell dedifferentiation as a mechanism of diabetic β cell failure. Cell 2012, 150:1223-1234.
73. Li Z., et al. Islet loss and alpha cell expansion in type 1 diabetes induced by multiple low-dose streptozotocin administration in mice. J. Endocrinol. 2000, 165:93-99.
74. Yano T., et al. Stromal cell derived factor-1 (SDF-1)/CXCL12 attenuates diabetes in mice and promotes pancreatic beta-cell survival by activation of the prosurvival kinase Akt. Diabetes 2007, 56:2946-2957.
75. Ellingsgaard H., et al. Interleukin-6 regulates pancreatic alpha-cell mass expansion. Proc. Natl. Acad. Sci. U.S.A. 2008, 105:13163-13168.
76. Liu Z., et al. Insulin and glucagon regulate pancreatic alpha-cell proliferation. PLoS ONE 2011, 6:e16096.
77. Ellingsgaard H., et al. Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells. Nat. Med. 2011, 17:1481-1489.
78. O'Reilly L.A., et al. Alpha-cell neogenesis in an animal model of IDDM. Diabetes 1997, 46:599-606.
79. Ogawa N., et al. Cure of overt diabetes in NOD mice by transient treatment with anti-lymphocyte serum and exendin-4. Diabetes 2004, 53:1700-1705.
80. Rydgren T., et al. Elevated glucagon-like plasma levels as a possible adaptive response in diabetic NOD mice. Biochem. Biophys. Res. Comm. 2012, 423:583-587.
81. Guardado-Mendoza R., et al. Pancreatic islet amyloidosis, beta-cell apoptosis, and alpha-cell proliferation are determinants of islet remodeling in type-2 diabetic baboons. Proc. Natl. Acad. Sci. U.S.A. 2009, 106:13992-13997.
82. Orci L., et al. Hypertrophy and hyperplasia of somatostatin-containing D-cells in diabetes. Proc. Natl. Acad. Sci. U.S.A. 1976, 73:1338-1342.
83. Waguri M., et al. Histopathologic study of the pancreas shows a characteristic lymphocytic infiltration in Japanese patients with IDDM. Endocr. J. 1997, 44:23-33.
84. Yoon K.H., et al. Selective beta-cell loss and alpha-cell expansion in patients with type 2 diabetes mellitus in Korea. J. Clin. Endocrinol. Metab. 2003, 88:2300-2308.
85. MaClean N., Ogilvie R.F. Quantitative estimation of the pancreatic islet tissue in diabetic subjects. Diabetes 1955, 4:367-376.
86. Clark A., et al. Islet amyloid, increased A-cells, reduced B-cells and exocrine fibrosis: quantitative changes in the pancreas in type 2 diabetes. Diabetes Res. 1988, 9:151-159.
87. Deng S., et al. Structural and functional abnormalities in the islets isolated from type 2 diabetic subjects. Diabetes 2004, 53:624-632.
88. Iki K., Pour P.M. Distribution of pancreatic endocrine cells including IAPP-expressing cells in non-diabetic and type 2 diabetic cases. J. Histochem. Cytochem. 2007, 55:111-118.
89. Henquin J.C., Rahier J. Pancreatic alpha cell mass in European subjects with type 2 diabetes. Diabetologia 2011, 54:1720-1725.
90. Marchetti P., et al. A local glucagon-like peptide 1 (GLP-1) system in human pancreatic islets. Diabetologia 2012, 55:3262-3272.
91. Mojsov S., et al. Both amidated and nonamidated forms of glucagon-like peptide I are synthesized in the rat intestine and the pancreas. J. Biol. Chem. 1990, 265:8001-8008.
92. Heller R.S., Aponte G.W. Intra-islet regulation of hormone secretion by glucagon-like peptide-1-(7-36) amide. Am. J. Physiol. 1995, 269:G852-G860.
93. Masur K., et al. Basal receptor activation by locally produced glucagon-like peptide-1 contributes to maintaining beta-cell function. Mol. Endocrinol. 2005, 19:1373-1382.
94. Habener J.F., Stanojevic V. Alpha cell role in beta cell generation and regeneration. Islets 2012, 4:188-198.
95. Vuguin P.M., et al. Ablation of the glucagon receptor gene increases fetal lethality and produces alterations in islet development and maturation. Endocrinology 2006, 147:3995-4006.
96. Yu R., et al. Pancreatic neuroendocrine tumors in glucagon receptor-deficient mice. PLoS ONE 2011, 6:e23397.
97. Furuta M., et al. Defective prohormone processing and altered pancreatic islet morphology in mice lacking active SPC2. Proc. Natl. Acad. Sci. U.S.A. 1997, 94:6646-6651.
98. Furuta M., et al. Severe defect in proglucagon processing in islet A-cells of prohormone convertase 2 null mice. J. Biol. Chem. 2001, 276:27197-27202.
99. Vincent M., et al. Abrogation of protein convertase 2 activity results in delayed islet cell differentiation and maturation, increased alpha-cell proliferation, and islet neogenesis. Endocrinology 2003, 144:4061-4069.
100. Gagnon J., et al. PCSK2-null mice exhibit delayed intestinal motility, reduced refeeding response and altered plasma levels of several regulatory peptides. Life Sci. 2011, 88:212-217.
101. Chen M., et al. Absence of the glucagon-like peptide-1 receptor does not affect the metabolic phenotype of mice with liver-specific G(s)alpha deficiency. Endocrinology 2011, 152:3343-3350.
102. Gu W., et al. Glucagon receptor antagonist-mediated improvements in glycemic control are dependent on functional pancreatic GLP-1 receptor. Am. J. Physiol. Endocrinol. Metab. 2010, 299:E624-E632.
103. Yu R., et al. A natural inactivating mutant of human glucagon receptor exhibits multiple abnormalities in processing and signaling. Endocrinol. Nutr. 2011, 58:258-266.
104. Zhou C., et al. Homozygous P86S mutation of the human glucagon receptor is associated with hyperglucagonemia, alpha cell hyperplasia, and islet cell tumor. Pancreas 2009, 38:941-946.
105. Imai J., et al. Regulation of pancreatic beta cell mass by neuronal signals from the liver. Sci. 2008, 322:1250-1254.
106. Michael M.D., et al. Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction. Mol. Cell 2000, 6:87-97.
107. Kayo T., et al. Developmental expression of proprotein-processing endoprotease furin in rat pancreatic islets. Endocrinology 1996, 137:5126-5134.
108. Marandi M., et al. Proprotein convertases 1 and 2 (PC1 and PC2) are expressed in neurally differentiated rat bone marrow stromal stem cells (BMSCs). Neurosci. Lett. 2007, 420:198-203.
109. Portela-Gomes G.M., et al. Prohormone convertases 1/3, 2, furin and protein 7B2 (Secretogranin V) in endocrine cells of the human pancreas. Regul. Pept. 2008, 146:117-124.
110. Grigoryan M., et al. Regulation of mouse intestinal L cell progenitors proliferation by the glucagon family of peptides. Endocrinology 2012, 153:3076-3088.
111. Edgerton D.S., Cherrington A.D. Glucagon as a critical factor in the pathology of diabetes. Diabetes 2011, 60:377-380.
112. Tomas E., Habener J.F. Insulin-like actions of glucagon-like peptide-1: a dual receptor hypothesis. Trends Endocrinol. Metab. 2010, 21:59-67.
113. Hupe-Sodmann K., et al. Characterisation of the processing by human neutral endopeptidase 24.11 of GLP-1(7-36) amide and comparison of the substrate specificity of the enzyme for other glucagon-like peptides. Regul. Pept. 1995, 58:149-156.
114. Tomas E., et al. GLP-1-derived nonapeptide GLP-1(28-36)amide targets to mitochondria and suppresses glucose production and oxidative stress in isolated mouse hepatocytes. Regul. Pept. 2011, 167:177-184.
115. Ip W., et al. GLP-1-derived nonapeptide GLP-1(28-36)amide reduces hepatic glucose production and represses the expression of gluconeogenic genes. Diabetes 2012, 61(Suppl. 1):464. ADA abstract 1804-P.
116. Liu Z., et al. GLP1-derived nonapeptide GLP1(28-36)amide protects pancreatic beta-cells from glucolipotoxicity. J. Endocrinol. 2012, 213:143-154.
117. Shao W., et al. GLP-1-derived nonapeptide GLP-1(28-36)amide stimulates the growth and function of pancreatic beta cell line INS-1 via activating the PKA-CREB signaling pathway. Diabetes 2012, 61(Suppl. 1):772. ADA abstract 2922-PO.
118. Tomas E., et al. GLP-1-derived nonapeptide GLP-1(28-36)amide inhibits weight gain and attenuates diabetes and hepatic steatosis in diet-induced obese mice. Regul. Pept. 2011, 169:43-48.
119. Tomas E., et al. GLP-1-derived pentapeptide GLP-1(32-36)amide attenuates the development of obesity, diabetes, hepatic steatosis, and increases energy expenditure in diet-induced obese mice. Diabetes 2012, 61(Suppl. 1):4980. ADA abstract 1915-P.
120. Standeven K.F., et al. Neprilysin, obesity and the metabolic syndrome. Int. J. Obes. (Lond.) 2011, 35:1031-1040.
121. Lee Y.S., et al. Glucagon-like peptide-1 gene therapy in obese diabetic mice results in long-term cure of diabetes by improving insulin sensitivity and reducing hepatic gluconeogenesis. Diabetes 2007, 56:1671-1679.
122. Tomas E., et al. GLP-1 (9-36) amide metabolite suppression of glucose production in isolated mouse hepatocytes. Horm. Metab. Res. 2010, 42:657-662.
123. Kimble P.C., Murlin J.R. Aqueous extracts of pancreas. III. Some precipitation reactions of insulin. J. Biol. Chem. 1923, 58:337-346.
124. Kieffer T.J., Habener J.F. The glucagon-like peptides. Endocr. Rev. 1999, 20:876-913.
125. Lovshin J.A., Drucker D.J. Incretin-based therapies for type 2 diabetes mellitus. Nat. Rev. Endocrinol. 2009, 5:262-269.
126. Brubaker P.L., Drucker D.J. Minireview: glucagon-like peptides regulate cell proliferation and apoptosis in the pancreas, gut, and central nervous system. Endocrinology 2004, 145:2653-2659.
127. Buteau J. GLP-1 receptor signaling: effects on pancreatic beta-cell proliferation and survival. Diabetes Metab. 2008, 34(Suppl. 2):S73-S77.
128. McIntosh C.H., et al. Pleiotropic actions of the incretin hormones. Vitam. Horm. 2010, 84:21-79.
129. Grieve D.J., et al. Emerging cardiovascular actions of the incretin hormone glucagon-like peptide-1, potential therapeutic benefits beyond glycaemic control?. Br. J. Pharmacol. 2009, 157:1340-1351.
130. Ussher J.R., Drucker D.J. Cardiovascular biology of the incretin system. Endocr. Rev. 2012, 33:187-215.
131. Perry T., Greig N.H. Enhancing central nervous system endogenous GLP-1 receptor pathways for intervention in Alzheimer's disease. Curr. Alzheimer Res. 2005, 2:377-385.
132. Salcedo I., et al. Neuroprotective and neurotrophic actions of glucagon-like peptide-1: an emerging opportunity to treat neurodegenerative and cerebrovascular disorders. Br. J. Pharmacol. 2012, 166:1586-1599.
133. Dubé P.E., Brubaker P.L. Frontiers in glucagon-like peptide-2: multiple actions, multiple mediators. Am. J. Physiol. Endocrinol. Metab. 2007, 293:E460-E465.
134. Rowland K.J., Brubaker P.L. The 'cryptic' mechanism of action of glucagon-like peptide-2. Am. J. Physiol Gastrointest. Liver Physiol. 2011, 301:G1-G8.
135. Abraham E.J., et al. Insulinotropic hormone glucagon-like peptide-1 differentiation of human pancreatic islet-derived progenitor cells into insulin-producing cells. Endocrinology 2002, 143:3152-3161.
136. Chai W., et al. Glucagon-like peptide 1 recruits microvasculature and increases glucose use in muscle via a nitric oxide-dependent mechanism. Diabetes 2012, 61:888-896.
137. Rodriguez-Diaz R., et al. Alpha cells secrete acetylcholine as a non-neuronal paracrine signal priming beta cell function in humans. Nat. Med. 2011, 17:888-892.
138. Elahi D., et al. GLP-1 (9-36) amide, cleavage product of GLP-1 (7-36)amide, is a glucoregulatory peptide. Obesity 2008, 16:1501-1509.