Betatrophin provides a new insight into diabetes treatment and lipid metabolism (Review)

Zhu,Jin‑Zhou; Yu,Chao‑Hui; Li,You‑Ming

doi:10.3892/br.2014.284

Betatrophin provides a new insight into diabetes treatment and lipid metabolism (Review)

Authors:
- Jin‑Zhou Zhu
- Chao‑Hui Yu
- You‑Ming Li
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Affiliations: Department of Gastroenterology and Hepatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
Published online on: May 20, 2014 https://doi.org/10.3892/br.2014.284
Pages: 447-451

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Abstract

Replenishing the insulin?producing ??cell mass is considered to be a potential cure for diabetes. A recent study identified a secreted protein, known as betatrophin, which potently induces pancreatic ??cell proliferation. Notably, a number of studies reportedly identified betatrophin, which is also known as lipasin, atypical angiopoietin?like 8 and refeeding?induced fat and liver protein, and considered to be a novel regulator in lipid metabolism according to the studies. The identification of betatrophin was considered to create novel opportunities for potential diabetes therapy. In the present study, the current knowledge of betatrophin is reviewed, with regards to its character and function in lipid homeostasis and pancreatic ??cell proliferation.

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1	Lam DW and LeRoith D: The worldwide diabetes epidemic. Curr Opin Endocrinol Diabetes Obes. 19:93–96. 2012. View Article : Google Scholar
2	Scheen AJ and Lefèbvre PJ: Insulin action in man. Diabetes Metab. 22:105–110. 1996.
3	Talchai C, Xuan S, Lin HV, Sussel L and Accili D: Pancreatic β cell dedifferentiation as a mechanism of diabetic β cell failure. Cell. 150:1223–1234. 2012.
4	Teodoro JS, Gomes AP, Varela AT, Duarte FV, Rolo AP and Palmeira CM: Uncovering the beginning of diabetes: the cellular redox status and oxidative stress as starting players in hyperglycemic damage. Mol Cell Biochem. 376:103–110. 2013. View Article : Google Scholar : PubMed/NCBI
5	Kabelitz D, Geissler EK, Soria B, Schroeder IS, Fändrich F and Chatenoud L: Toward cell-based therapy of type I diabetes. Trends Immunol. 29:68–74. 2008. View Article : Google Scholar : PubMed/NCBI
6	Bonner-Weir S and Weir GC: New sources of pancreatic beta-cells. Nat Biotechnol. 23:857–861. 2005.
7	Michael MD, Kulkarni RN, Postic C, et al: Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction. Mol Cell. 6:87–97. 2000. View Article : Google Scholar : PubMed/NCBI
8	El Ouaamari A, Kawamori D, Dirice E, et al: Liver-derived systemic factors drive β cell hyperplasia in insulin-resistant states. Cell Rep. 3:401–410. 2013.PubMed/NCBI
9	Tang T, Li L, Tang J, et al: A mouse knockout library for secreted and transmembrane proteins. Nat Biotechnol. 28:749–755. 2010. View Article : Google Scholar : PubMed/NCBI
10	Teslovich TM, Musunuru K, Smith AV, et al: Biological, clinical and population relevance of 95 loci for blood lipids. Nature. 466:707–713. 2010. View Article : Google Scholar : PubMed/NCBI
11	Yi P, Park JS and Melton DA: Betatrophin: a hormone that controls pancreatic β cell proliferation. Cell. 153:747–758. 2013.
12	Fu Z, Yao F, Abou-Samra AB and Zhang R: Lipasin, thermoregulated in brown fat, is a novel but atypical member of the angiopoietin-like protein family. Biochem Biophys Res Commun. 430:1126–1131. 2013. View Article : Google Scholar : PubMed/NCBI
13	Zhang R: Lipasin, a novel nutritionally-regulated liver-enriched factor that regulates serum triglyceride levels. Biochem Biophys Res Commun. 424:786–792. 2012. View Article : Google Scholar : PubMed/NCBI
14	Quagliarini F, Wang Y, Kozlitina J, et al: Atypical angiopoietin-like protein that regulates ANGPTL3. Proc Natl Acad Sci USA. 109:19751–19756. 2012. View Article : Google Scholar : PubMed/NCBI
15	Ren G, Kim JY and Smas CM: Identification of RIFL, a novel adipocyte-enriched insulin target gene with a role in lipid metabolism. Am J Physiol Endocrinol Metab. 303:E334–E351. 2012. View Article : Google Scholar : PubMed/NCBI
16	Mattijssen F and Kersten S: Regulation of triglyceride metabolism by Angiopoietin-like proteins. Biochim Biophys Acta. 1821.782–789. 2012.PubMed/NCBI
17	Oike Y and Tabata M: Angiopoietin-like proteins - potential therapeutic targets for metabolic syndrome and cardiovascular disease. Circ J. 73:2192–2197. 2009.PubMed/NCBI
18	Li C: Genetics and regulation of angiopoietin-like proteins 3 and 4. Curr Opin Lipidol. 17:152–156. 2006. View Article : Google Scholar : PubMed/NCBI
19	Miida T and Hirayama S: Impacts of angiopoietin-like proteins on lipoprotein metabolism and cardiovascular events. Curr Opin Lipidol. 21:70–75. 2010. View Article : Google Scholar : PubMed/NCBI
20	Musunuru K, Pirruccello JP, Do R, et al: Exome sequencing, ANGPTL3 mutations and familial combined hypolipidemia. N Engl J Med. 363:2220–2227. 2010. View Article : Google Scholar : PubMed/NCBI
21	Romeo S, Yin W, Kozlitina J, et al: Rare loss-of-function mutations in ANGPTL family members contribute to plasma triglyceride levels in humans. J Clin Invest. 119:70–79. 2009.PubMed/NCBI
22	Koishi R, Ando Y, Ono M, et al: Angptl3 regulates lipid metabolism in mice. Nat Genet. 30:151–157. 2002. View Article : Google Scholar : PubMed/NCBI
23	Romeo S, Pennacchio LA, Fu Y, et al: Population-based resequencing of ANGPTL4 uncovers variations that reduce triglycerides and increase HDL. Nat Genet. 39:513–516. 2007. View Article : Google Scholar : PubMed/NCBI
24	Inukai K, Nakashima Y, Watanabe M, et al: ANGPTL3 is increased in both insulin-deficient and -resistant diabetic states. Biochem Biophys Res Commun. 317:1075–1079. 2004. View Article : Google Scholar : PubMed/NCBI
25	Yoon JC, Chickering TW, Rosen ED, et al: Peroxisome proliferator-activated receptor gamma target gene encoding a novel angiopoietin-related protein associated with adipose differentiation. Mol Cell Biol. 20:5343–5349. 2000. View Article : Google Scholar : PubMed/NCBI
26	Wang Y, Quagliarini F, Gusarova V, et al: Mice lacking ANGPTL8 (Betatrophin) manifest disrupted triglyceride metabolism without impaired glucose homeostasis. Proc Natl Acad Sci USA. 110:16109–16114. 2013. View Article : Google Scholar
27	Flier SN, Kulkarni RN and Kahn CR: Evidence for a circulating islet cell growth factor in insulin-resistant states. Proc Natl Acad Sci USA. 98:7475–7480. 2001. View Article : Google Scholar : PubMed/NCBI
28	Kulkarni RN, Mizrachi EB, Ocana AG and Stewart AF: Human β-cell proliferation and intracellular signaling: driving in the dark without a road map. Diabetes. 61:2205–2213. 2012.
29	Kinsey-Jones JS and Murphy KG: Current models and strategies in the development of antiobesity drugs. Ann NY Acad Sci. 1245:3–6. 2011. View Article : Google Scholar : PubMed/NCBI
30	Aydin S, Kuloglu T, Aydin S, et al: Expression of adropin in rat brain, cerebellum, kidneys, heart, liver and pancreas in streptozotocin-induced diabetes. Mol Cell Biochem. 380:73–81. 2013. View Article : Google Scholar : PubMed/NCBI
31	Imai J, Katagiri H, Yamada T, et al: Regulation of pancreatic β cell mass by neuronal signals from the liver. Science. 322:1250–1254. 2008.
32	Jiao Y, Le Lay J, Yu M, Naji A and Kaestner KH: Elevated mouse hepatic betatrophin expression does not increase human β-cell replication in the transplant setting. Diabetes. 63:1283–1288. 2014.PubMed/NCBI
33	Espes D, Lau J and Carlsson PO: Increased circulating levels of betatrophin in individuals with long-standing type 1 diabetes. Diabetologia. 57:50–53. 2014. View Article : Google Scholar : PubMed/NCBI
34	Raghow R: Betatrophin: a liver-derived hormone for the pancreatic β-cell proliferation. World J Diabetes. 4:234–237. 2013.PubMed/NCBI
35	Zhang R and Abou-Samra AB: Emerging roles of lipasin as a critical lipid regulator. Biochem Biophys Res Commun. 432:401–405. 2013. View Article : Google Scholar : PubMed/NCBI
36	Smukler SR, Arntfield ME, Razavi R, et al: The adult mouse and human pancreas contain rare multipotent stem cells that express insulin. Cell Stem Cell. 8:281–293. 2011. View Article : Google Scholar : PubMed/NCBI
37	Kushner JA: The role of aging upon β cell turnover. J Clin Invest. 123:990–995. 2013.
38	Boström P, Wu J, Jedrychowski MP, et al: A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 481:463–468. 2012.
39	Novelle MG, Contreras C, Romero-Picó A, López M and Diéguez C: Irisin, two years later. Int J Endocrinol. 2013:7462812013.PubMed/NCBI
40	Zhang Y, Li R, Meng Y, et al: Irisin stimulates browning of white adipocytes through mitogen-activated protein kinase p38 MAP kinase and ERK MAP kinase signaling. Diabetes. 63:514–525. 2014. View Article : Google Scholar : PubMed/NCBI
41	Sanchis-Gomar F and Perez-Quilis C: The p38-PGC-1α-irisin-betatrophin axis: exploring new pathways in insulin resistance. Adipocyte. 3:67–68. 2014.