Do sodium-glucose co-transporter-2 inhibitors prevent heart failure with a preserved ejection fraction by counterbalancing the effects of leptin? A novel hypothesis

Diabetes, Obesity and Metabolism

Volumn 20, Issue 6, 2018, Pages 1361-1366

  Packer, Milton ^a  

^a BAYLOR UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

antidiabetic drug; cardiovascular disease; SGLT2 inhibitor

Indexed keywords

LEPTIN; SODIUM GLUCOSE COTRANSPORTER 2; SODIUM GLUCOSE COTRANSPORTER 2 INHIBITOR; ANTIDIABETIC AGENT; LEP PROTEIN, HUMAN; SLC5A2 PROTEIN, HUMAN;

ADIPOSE TISSUE; ARTICLE; CLINICAL TRIAL (TOPIC); DIABETES MELLITUS; DIURETIC ACTIVITY; DRUG EFFECT; DRUG MECHANISM; HEART FAILURE WITH PRESERVED EJECTION FRACTION; HEART MUSCLE FIBROSIS; HEART PROTECTION; HORMONAL REGULATION; HORMONE ACTION; HORMONE RELEASE; HORMONE SYNTHESIS; HUMAN; INFLAMMATION; KIDNEY FIBROSIS; KIDNEY FUNCTION; KIDNEY TUBULE; NEPHRITIS; NON INSULIN DEPENDENT DIABETES MELLITUS; OBESITY; PHENOTYPE; PLASMA VOLUME; PROTEIN EXPRESSION; SODIUM RETENTION; ANIMAL; ANTAGONISTS AND INHIBITORS; BIOLOGICAL MODEL; CARDIAC MUSCLE; CHEMISTRY; COMPLICATION; DIABETIC CARDIOMYOPATHY; DIABETIC NEPHROPATHY; HEART; HEART FAILURE; HEART STROKE VOLUME; IMMUNOLOGY; INTRA-ABDOMINAL FAT; KIDNEY FAILURE; METABOLISM; PATHOPHYSIOLOGY;

ANIMALS; DIABETES MELLITUS, TYPE 2; DIABETIC CARDIOMYOPATHIES; DIABETIC NEPHROPATHIES; HEART; HEART FAILURE; HUMANS; HYPOGLYCEMIC AGENTS; INTRA-ABDOMINAL FAT; KIDNEY TUBULES; LEPTIN; MODELS, BIOLOGICAL; MYOCARDIUM; OBESITY; RENAL INSUFFICIENCY; SODIUM-GLUCOSE TRANSPORTER 2; SODIUM-GLUCOSE TRANSPORTER 2 INHIBITORS; STROKE VOLUME;

EID: 85042173880     PISSN: 14628902     EISSN: 14631326     Source Type: Journal    
DOI: 10.1111/dom.13229     Document Type: Article

References (99)

1. Zinman B, Wanner C, Lachin JM, et al.; EMPA-REG OUTCOME Investigators Empagliflozin, cardiovascular out-comes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117-2128.
2. Neal B, Perkovic V, Mahaffey KW, et al.; CANVAS Program Collaborative Group Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377:644-657.
3. Hallow KM, Helmlinger G, Greasley PJ, McMurray JJV, Boulton DW. Why do SGLT2 inhibitors reduce heart failure hospitalization? A differential volume regulation hypothesis. Diabetes Obes Metab. 2018;20:479–487.
4. Packer M. Role of the sodium-hydrogen exchanger in mediating the renal effects of drugs commonly used in the treatment of type 2 diabetes. Diabetes Obes Metab. 2018;20:800–811.
5. Pessoa TD, Campos LC, Carraro-Lacroix L, Girardi AC, Malnic G. Functional role of glucose metabolism, osmotic stress, and sodium-glucose cotransporter isoform-mediated transport on Na+/H+ exchanger isoform 3 activity in the renal proximal tubule. J Am Soc Nephrol. 2014;25:2028-2039.
6. Joubert M, Jagu B, Montaigne D, et al. The sodium-glucose cotransporter 2 inhibitor dapagliflozin prevents cardiomyopathy in a diabetic lipodystrophic mouse model. Diabetes. 2017;66:1030-1040.
7. Marso SP, Daniels GH, Brown-Frandsen K, et al.; LEADER Steering Committee; LEADER Trial Investigators Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:311-322.
8. Ferrannini E, Mark M, Mayoux E. CV protection in the EMPA-REG OUTCOME trial: a "thrifty substrate" hypothesis. Diabetes Care. 2016;39:1108-1114.
9. Aubert G, Martin OJ, Horton JL, et al. The failing heart relies on ketone bodies as a fuel. Circulation. 2016;133(8):698-705.
10. Uthman L, Baartscheer A, Bleijlevens B, et al. Class effects of SGLT2 inhibitors in mouse cardiomyocytes and hearts: inhibition of Na+/H+ exchanger, lowering of cytosolic Na+ and vasodilation. Diabetologia. 2017. https://doi.org/10.1007/s00125-017-4509-7. [Epub ahead of print].
11. Kusaka H, Koibuchi N, Hasegawa Y, Ogawa H, Kim-Mitsuyama S. Empagliflozin lessened cardiac injury and reduced visceral adipocyte hypertrophy in prediabetic rats with metabolic syndrome. Cardiovasc Diabetol. 2016;15(1):157.
12. Zhao Y, Xu L, Tian D, et al. Effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on serum uric acid level: A meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2018;20(2):458-462.
13. Altara R, Giordano M, Nordén ES, et al. Targeting obesity and diabetes to treat heart failure with preserved ejection fraction. Front Endocrinol (Lausanne). 2017;8:160. https://doi.org/10.3389/fendo.2017.00160.
14. Obokata M, Reddy YNV, Pislaru SV, Melenovsky V, Borlaug BA. Evidence supporting the existence of a distinct obese phenotype of heart failure with preserved ejection fraction. Circulation. 2017;136:6-19.
15. Schelbert EB, Fridman Y, Wong TC, et al. Temporal relation between myocardial fibrosis and heart failure with preserved ejection fraction: association with baseline disease severity and subsequent outcome. JAMA Cardiol. 2017;2:995-1006.
16. Reddy YN, Melenovsky V, Redfield MM, Nishimura RA, Borlaug BA. High-output heart failure: a 15-year experience. J Am Coll Cardiol. 2016;68:473-482.
17. Hage C, Michaëlsson E, Linde C, et al. Inflammatory biomarkers predict heart failure severity and prognosis in patients with heart failure with preserved ejection fraction: a holistic proteomic approach. Circ Cardiovasc Genet. 2017;10(1):e001633. https://doi.org/10.1161/CIRCGENETICS.116.001633.
18. Goodfriend TL, Kelley DE, Goodpaster BH, Winters SJ. Visceral obesity and insulin resistance are associated with plasma aldosterone levels in women. Obes Res. 1999;7:355-362.
19. Standeven KF, Hess K, Carter AM, et al. Neprilysin, obesity and the metabolic syndrome. Int J Obes (Lond). 2011;35:1031-1040.
20. Wauters M, Considine RV, Yudkin JS, Peiffer F, De Leeuw I, Van Gaal LF. Leptin levels in type 2 diabetes: associations with measures of insulin resistance and insulin secretion. Horm Metab Res. 2003;35:92-96.
21. Mark AL. Selective leptin resistance revisited. Am J Physiol Regul Integr Comp Physiol. 2013;305:R566-R581.
22. Pandit R, Beerens S, Adan RAH. Role of leptin in energy expenditure: the hypothalamic perspective. Am J Physiol Regul Integr Comp Physiol. 2017;312:R938-R947.
23. Xue B, Yu Y, Zhang Z, et al. Leptin mediates high-fat diet sensitization of angiotensin II-elicited hypertension by upregulating the brain renin-angiotensin system and inflammation. Hypertension. 2016;67:970-976.
24. Lim K, Barzel B, Burke SL, Armitage JA, Head GA. Origin of aberrant blood pressure and sympathetic regulation in diet-induced obesity. Hypertension. 2016;68:491-500.
25. Ben-Zvi D, Savion N, Kolodgie F, et al. Local application of leptin antagonist attenuates angiotensin II-induced ascending aortic aneurysm and cardiac remodeling. J Am Heart Assoc. 2016;5(5):e003474. https://doi.org/10.1161/JAHA.116.003474.
26. Payne GA, Borbouse L, Kumar S, et al. Epicardial perivascular adipose-derived leptin exacerbates coronary endothelial dysfunction in metabolic syndrome via a protein kinase C-beta pathway. Arterioscler Thromb Vasc Biol. 2010;30:1711-1717.
27. Huby AC, Antonova G, Groenendyk J, et al. Adipocyte-derived hormone leptin is a direct regulator of aldosterone secretion, which promotes endothelial dysfunction and cardiac fibrosis. Circulation. 2015;132:2134-2145.
28. Briones AM, Nguyen Dinh Cat A, Callera GE, et al. Adipocytes produce aldosterone through calcineurin-dependent signaling pathways: implications in diabetes mellitus-associated obesity and vascular dysfunction. Hypertension. 2012;59(5):1069-1078.
29. Lütken SC, Kim SW, Jonassen T, et al. Changes of renal AQP2, ENaC, and NHE3 in experimentally induced heart failure: response to angiotensin II AT1 receptor blockade. Am J Physiol Renal Physiol. 2009;297:F1678-F1688.
30. Morgan DA, Thedens DR, Weiss R, Rahmouni K. Mechanisms mediating renal sympathetic activation to leptin in obesity. Am J Physiol Regul Integr Comp Physiol. 2008;295:R1730-R1736.
31. Kassab S, Kato T, Wilkins FC, Chen R, Hall JE, Granger JP. Renal denervation attenuates the sodium retention and hypertension associated with obesity. Hypertension. 1995;25(4 pt 2):893-897.
32. Polhemus DJ, Trivedi RK, Gao J, et al. Renal sympathetic denervation protects the failing heart via inhibition of neprilysin activity in the kidney. J Am Coll Cardiol. 2017;70:2139-2153.
33. Bełtowski J. Leptin and the regulation of renal sodium handling and renal Na-transporting ATPases: role in the pathogenesis of arterial hypertension. Curr Cardiol Rev. 2010;6:31-40.
34. Karayannis G, Giamouzis G, Tziolas N, et al. Association between epicardial fat thickness and weight homeostasis hormones in patients with noncachectic heart failure. Angiology. 2013;64:173-180.
35. Machinal F, Dieudonne MN, Leneveu MC, Pecquery R, Giudicelli Y. In vivo and in vitro ob gene expression and leptin secretion in rat adipocytes: evidence for a regional specific regulation by sex steroid hormones. Endocrinology. 1999;140:1567-1574.
36. Zheng D, Jones JP, Usala SJ, Dohm GL. Differential expression of ob mRNA in rat adipose tissues in response to insulin. Biochem Biophys Res Commun. 1996;218:434-437.
37. Iacobellis G, Diaz S, Mendez A, Goldberg R. Increased epicardial fat and plasma leptin in type 1 diabetes independently of obesity. Nutr Metab Cardiovasc Dis. 2014;24:725-729.
38. Lieb W, Sullivan LM, Harris TB, et al. Plasma leptin levels and incidence of heart failure, cardiovascular disease, and total mortality in elderly individuals. Diabetes Care. 2009;32:612-616.
39. Pedone C, Roshanravan B, Scarlata S, Patel KV, Ferrucci L, Incalzi RA. Longitudinal association between serum leptin concentration and glomerular filtration rate in humans. PLoS One. 2015;10(2):e0117828. https://doi.org/10.1371/journal.pone.0117828.
40. Sarnak MJ, Poindexter A, Wang SR, et al. Serum C-reactive protein and leptin as predictors of kidney disease progression in the Modification of Diet in Renal Disease Study. Kidney Int. 2002;62:2208-2215.
41. Faxén UL, Hage C, Andreasson A, et al. HFpEF and HFrEF exhibit different phenotypes as assessed by leptin and adiponectin. Int J Cardiol. 2017;228:709-716.
42. Iacobellis G. Local and systemic effects of the multifaceted epicardial adipose tissue depot. Nat Rev Endocrinol. 2015;11:363-371.
43. Wu CK, Tsai HY, Su MM, et al. Evolutional change in epicardial fat and its correlation with myocardial diffuse fibrosis in heart failure patients. J Clin Lipidol. 2017;11(6):1421-1431.
44. Zhang X, Li ZL, Woollard JR, et al. Obesity-metabolic derangement preserves hemodynamics but promotes intrarenal adiposity and macrophage infiltration in swine renovascular disease. Am J Physiol Renal Physiol. 2013;305:F265-F276.
45. Zibadi S, Cordova F, Slack EH, Watson RR, Larson DF. Leptin's regulation of obesity-induced cardiac extracellular matrix remodeling. Cardiovasc Toxicol. 2011;11:325-333.
46. Chiba Y, Yamada T, Tsukita S, et al. Dapagliflozin, a sodium-glucose co-transporter 2 inhibitor, acutely reduces energy expenditure in BAT via neural signals in mice. PLoS One. 2016;11(3):e0150756. https://doi.org/10.1371/journal.pone.0150756.
47. Jordan J, Tank J, Heusser K, et al. The effect of empagliflozin on muscle sympathetic nerve activity in patients with type II diabetes mellitus. J Am Soc Hypertens. 2017;11(9):604-612. https://doi.org/10.1016/j.jash.2017.07.005.
48. Matthews VB, Elliot RH, Rudnicka C, Hricova J, Herat L, Schlaich MP. Role of the sympathetic nervous system in regulation of the sodium glucose cotransporter 2. J Hypertens. 2017;35:2059-2068.
49. Rafiq K, Fujisawa Y, Sherajee SJ, et al. Role of the renal sympathetic nerve in renal glucose metabolism during the development of type 2 diabetes in rats. Diabetologia. 2015;58:2885-2898.
50. Bautista R, Manning R, Martinez F, et al. Angiotensin II-dependent increased expression of Na+-glucose cotransporter in hypertension. Am J Physiol Renal Physiol. 2004;286:F127-F133.
51. Petrykiv S, Laverman GD, de Zeeuw D, Heerspink HJL. Does SGLT2 inhibition with dapagliflozin overcome individual therapy resistance to RAAS inhibition? Diabetes Obes Metab. 2018;20:224-227.
52. Vallon V, Platt KA, Cunard R, et al. SGLT2 mediates glucose reabsorption in the early proximal tubule. J Am Soc Nephrol. 2011;22:104-112.
53. Weir MR, Kline I, Xie J, Edwards R, Usiskin K. Effect of canagliflozin on serum electrolytes in patients with type 2 diabetes in relation to estimated glomerular filtration rate (eGFR). Curr Med Res Opin. 2014;30:1759-1768.
54. Miyaoka D, Tsuda A, Hayashi N, et al. Development of hyperkalemia following treatment with dapagliflozin (DAPA) in a patient with type 2 diabetes after bilateral adrenalectomy. CEN Case Rep. 2017. https://doi.org/10.1007/s13730-017-0286-x. [Epub ahead of print].
55. Ye Y, Bajaj M, Yang HC, Perez-Polo JR, Birnbaum Y. SGLT-2 inhibition with dapagliflozin reduces the activation of the Nlrp3/ASC inflammasome and attenuates the development of diabetic cardiomyopathy in mice with type 2 diabetes. Further augmentation of the effects with saxagliptin, a DPP4 inhibitor. Cardiovasc Drugs Ther. 2017;31:119-132.
56. Lee TM, Chang NC, Lin SZ. Dapagliflozin, a selective SGLT2 Inhibitor, attenuated cardiac fibrosis by regulating the macrophage polarization via STAT3 signaling in infarcted rat hearts. Free Radic Biol Med. 2017;104:298-310.
57. Leifheit-Nestler M, Wagner NM, Gogiraju R, et al. Importance of leptin signaling and signal transducer and activator of transcription-3 activation in mediating the cardiac hypertrophy associated with obesity. J Transl Med. 2013;11:170. https://doi.org/10.1186/1479-5876-11-170.
58. Martínez-Martínez E, Jurado-López R, Valero-Muñoz M, et al. Leptin induces cardiac fibrosis through galectin-3, mTOR and oxidative stress: potential role in obesity. J Hypertens. 2014;32(5):1104-1114. https://doi.org/10.1097/HJH.0000000000000149.
59. Konstantinou-Tegou A, Kaloyianni M, Bourikas D, Koliakos G. The effect of leptin on Na(+)-H(+) antiport (NHE 1) activity of obese and normal subjects erythrocytes. Mol Cell Endocrinol. 2001;183(1-2):11-18.
60. Ishibashi Y, Matsui T, Yamagishi S. Tofogliflozin, a highly selective inhibitor of SGLT2 blocks proinflammatory and proapoptotic effects of glucose overload on proximal tubular cells partly by suppressing oxidative stress generation. Horm Metab Res. 2016;48:191-195.
61. Lambert R, Srodulski S, Peng X, Margulies KB, Despa F, Despa S. Intracellular Na+ Concentration ([Na+]i) is elevated in diabetic hearts due to enhanced Na+-glucose cotransport. J Am Heart Assoc. 2015;4(9):e002183. https://doi.org/10.1161/JAHA.115.002183.
62. Baartscheer A, Schumacher CA, Wüst RC, et al. Empagliflozin decreases myocardial cytoplasmic Na+ through inhibition of the cardiac Na+/H+ exchanger in rats and rabbits. Diabetologia. 2017;60:568-573.
63. Suzuki M, Honda K, Fukazawa M, et al. Tofogliflozin, a potent and highly specific sodium/glucose cotransporter 2 inhibitor, improves glycemic control in diabetic rats and mice. J Pharmacol Exp Ther. 2012;341:692-701.
64. Gembardt F, Bartaun C, Jarzebska N, et al. The SGLT2 inhibitor empagliflozin ameliorates early features of diabetic nephropathy in BTBR ob/ob type 2 diabetic mice with and without hypertension. Am J Physiol Renal Physiol. 2014;307:F317-F325.
65. Bolinder J, Ljunggren Ö, Kullberg J, et al. Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin. J Clin Endocrinol Metab. 2012;97:1020-1031.
66. Blonde L, Stenlöf K, Fung A, Xie J, Canovatchel W, Meininger G. Effects of canagliflozin on body weight and body composition in patients with type 2 diabetes over 104 weeks. Postgrad Med. 2016;128:371-380.
67. Vickers SP, Cheetham SC, Headland KR, et al. Combination of the sodium-glucose cotransporter-2 inhibitor empagliflozin with orlistat or sibutramine further improves the body-weight reduction and glucose homeostasis of obese rats fed a cafeteria diet. Diabetes Metab Syndr Obes. 2014;7:265-275. https://doi.org/10.2147/DMSO.S58786.
68. Napolitano A, Miller S, Murgatroyd PR, et al. Exploring glycosuria as a mechanism for weight and fat mass reduction. A pilot study with remogliflozin etabonate and sergliflozin etabonate in healthy obese subjects. J Clin Transl Endocrinol. 2013;1(1):e3-e8. https://doi.org/10.1016/j.jcte.2013.12.001.
69. Fontana L, Eagon JC, Trujillo ME, Scherer PE, Klein S. Visceral fat adipokine secretion is associated with systemic inflammation in obese humans. Diabetes. 2007;56:1010-1013.
70. Zumbach MS, Boehme MW, Wahl P, Stremmel W, Ziegler R, Nawroth PP. Tumor necrosis factor increases serum leptin levels in humans. J Clin Endocrinol Metab. 1997;82:4080-4082.
71. Cherian S, Lopaschuk GD, Carvalho E. Cellular cross-talk between epicardial adipose tissue and myocardium in relation to the pathogenesis of cardiovascular disease. Am J Physiol Endocrinol Metab. 2012;303:E937-E949.
72. Yagi S, Hirata Y, Ise T, et al. Canagliflozin reduces epicardial fat in patients with type 2 diabetes mellitus. Diabetol Metab Syndr. 2017;9:78. https://doi.org/10.1186/s13098-017-0275-4.
73. Díaz-Rodríguez E, Agra RM, Fernández ÁL, et al. Novel effects of dapagliflozin on epicardial adipose tissue with insulin resistance, high levels of inflammatory chemokines production and low differentiation ability. Cardiovasc Res. 2017;114:336-346. https://doi.org/10.1093/cvr/cvx186.
74. Bouchi R, Terashima M, Sasahara Y, et al. Luseogliflozin reduces epicardial fat accumulation in patients with type 2 diabetes: a pilot study. Cardiovasc Diabetol. 2017;16(1):32. https://doi.org/10.1186/s12933-017-0516-8.
75. Fukuda T, Bouchi R, Terashima M, et al. Ipragliflozin reduces epicardial fat accumulation in non-obese type 2 diabetic patients with visceral obesity: a pilot study. Diabetes Ther. 2017;8:851-861.
76. Teta D, Bevington A, Brown J, Pawluczyk I, Harris K, Walls J. Acidosis downregulates leptin production from cultured adipocytes through a glucose transport-dependent post-transcriptional mechanism. J Am Soc Nephrol. 2003;14:2248-2254.
77. Fadini GP, Bonora BM, Zatti G, et al. Effects of the SGLT2 inhibitor dapagliflozin on HDL cholesterol, particle size, and cholesterol efflux capacity in patients with type 2 diabetes: a randomized placebo-controlled trial. Cardiovasc Diabetol. 2017;16(1):42. https://doi.org/10.1186/s12933-017-0529-3.
78. Fruehwald-Schultes B, Oltmanns KM, Toschek B, et al. Short-term treatment with metformin decreases serum leptin concentration without affecting body weight and body fat content in normal-weight healthy men. Metabolism. 2002;51:531-536.
79. Qi T, Chen Y, Li H, et al. A role for PFKFB3/iPFK2 in metformin suppression of adipocyte inflammatory responses. J Mol Endocrinol. 2017;59:49-59.
80. Iacobellis G, Mohseni M, Bianco SD, Banga PK. Liraglutide causes large and rapid epicardial fat reduction. Obesity (Silver Spring). 2017;25:311-316.
81. Pastel E, McCulloch LJ, Ward R, et al. GLP-1 analogue-induced weight loss does not improve obesity-induced AT dysfunction. Clin Sci (Lond). 2017;131:343-353.
82. Masuda T, Fu Y, Eguchi A, et al. Dipeptidyl peptidase IV inhibitor lowers PPARγ agonist-induced body weight gain by affecting food intake, fat mass, and beige/brown fat but not fluid retention. Am J Physiol Endocrinol Metab. 2014;306(4):E388-E398.
83. Kim D, Kim J, Yoon JH, et al. CXCL12 secreted from adipose tissue recruits macrophages and induces insulin resistance in mice. Diabetologia. 2014;57:1456-1465.
84. Mulvihill EE, Varin EM, Ussher JR, et al. Inhibition of dipeptidyl peptidase-4 impairs ventricular function and promotes cardiac fibrosis in high fat-fed diabetic mice. Diabetes. 2016;65:742-754.
85. Díaz-Soto G, de Luis DA, Conde-Vicente R, Izaola-Jauregui O, Ramos C, Romero E. Beneficial effects of liraglutide on adipocytokines, insulin sensitivity parameters and cardiovascular risk biomarkers in patients with Type 2 diabetes: a prospective study. Diabetes Res Clin Pract. 2014;104:92-96.
86. Shirakawa J, Fujii H, Ohnuma K, et al. Diet-induced adipose tissue inflammation and liver steatosis are prevented by DPP-4 inhibition in diabetic mice. Diabetes. 2011;60:1246-1257.
87. Al-Barazanji KA, Arch JR, Buckingham RE, Tadayyon M. Central exendin-4 infusion reduces body weight without altering plasma leptin in (fa/fa) Zucker rats. Obes Res. 2000;8:317-323.
88. US Food and Drug Administration. Diabetes medications containing saxagliptin and alogliptin: drug safety communication - risk of heart failure. April 5, 2016. https://www.fda.gov/safety/medwatch/safetyinformation/safetyalertsforhumanmedicalproducts/ucm494252.htm. Accessed December 18, 2017.
89. Smits MM, Tonneijck L, Muskiet MH, et al. Heart rate acceleration with GLP-1 receptor agonists in type 2 diabetes patients: an acute and 12-week randomised, double-blind, placebo-controlled trial. Eur J Endocrinol. 2017;176:77-86.
90. Gaspari T, Brdar M, Lee HW, et al. Molecular and cellular mechanisms of glucagon-like peptide-1 receptor agonist-mediated attenuation of cardiac fibrosis. Diab Vasc Dis Res. 2016;13:56-68.
91. Kyhl K, Lønborg J, Hartmann B, et al. Lack of effect of prolonged treatment with liraglutide on cardiac remodeling in rats after acute myocardial infarction. Peptides. 2017;93:1-12.
92. Sakai T, Kusakabe T, Ebihara K, et al. Leptin restores the insulinotropic effect of exenatide in a mouse model of type 2 diabetes with increased adiposity induced by streptozotocin and high-fat diet. Am J Physiol Endocrinol Metab. 2014;307:E712-E719.
93. Zhao S, Kanoski SE, Yan J, Grill HJ, Hayes MR. Hindbrain leptin and glucagon-like-peptide-1 receptor signaling interact to suppress food intake in an additive manner. Int J Obes (Lond). 2012;36:1522-1528.
94. Nowak A, Bojanowska E. Effects of peripheral or central GLP-1 receptor blockade on leptin-induced suppression of appetite. J Physiol Pharmacol. 2008;59:501-510.
95. Devenny JJ, Godonis HE, Harvey SJ, Rooney S, Cullen MJ, Pelleymounter MA. Weight loss induced by chronic dapagliflozin treatment is attenuated by compensatory hyperphagia in diet-induced obese (DIO) rats. Obesity (Silver Spring). 2012;20:1645-1652.
96. Lee YH, Magkos F, Mantzoros CS, Kang ES. Effects of leptin and adiponectin on pancreatic β-cell function. Metabolism. 2011;60:1664-1672.
97. Takahara M, Shiraiwa T, Matsuoka TA, Katakami N, Shimomura I. Ameliorated pancreatic β cell dysfunction in type 2 diabetic patients treated with a sodium-glucose cotransporter 2 inhibitor ipragliflozin. Endocr J. 2015;62:77-86.
98. Bonzón-Kulichenko E, Fernández-Agulló T, Moltó E, et al. Regulation of insulin-stimulated glucose uptake in rat white adipose tissue upon chronic central leptin infusion: effects on adiposity. Endocrinology. 2011;152:1366-1377.
99. Ducroc R, Guilmeau S, Akasbi K, Devaud H, Buyse M, Bado A. Luminal leptin induces rapid inhibition of active intestinal absorption of glucose mediated by sodium-glucose cotransporter 1. Diabetes. 2005;54:348-354.