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Glucagon increase after chronic AT1 blockade is more likely related to an indirect leptin-dependent than to a pancreatic α-cell-dependent mechanism

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Abstract

AT1 blockers (ARB) prevent diabetes by improving pancreatic β cell function. Less is known about whether α cells are affected although they express angiotensin II (AngII) receptors. We aimed to investigate glucagon release upon AngII stimulation. We determined glucagon release after AngII stimulation (0.01–100 μM) in α cells (InR1G9) and isolated murine islets. We determined plasma glucagon in rats that were chronically treated with AngII (9 μg/h) or the ARBs telmisartan (8 mg/kg/day) and candesartan (16 mg/kg/day) and correlated glucagon with additional hormones (e.g. leptin). Glucagon was only released from InR1G9 cells and islets at the highest AngII concentrations (>10 μM). This was not inhibited by losartan or PD123319. Ang(1-7) and AngIV were also almost ineffective. AngII did not alter glucagon secretion from islets. Plasma glucagon increased when obese Zucker rats were treated with AngII or candesartan and also when Sprague Dawley rats were treated with telmisartan in parallel to high-calorie feeding. Plasma glucagon and leptin negatively correlated in ARB-treated rats. The glucagon release from InR1G9 cells or islets after AngII, AngIV or Ang(1-7) is unspecific since it only occurs, if at all, after the highest concentrations and cannot be blocked by specific inhibitors. Thus, the AngII-dependent increase in plasma glucagon seems to be mediated by indirect mechanisms. The negative correlations between plasma leptin and glucagon confirm findings showing that leptin suppresses glucagon release, leading us to suppose that the increase in plasma glucagon is related to the decrease in leptin after ARB treatment.

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Abbreviations

AMLO:

Amlodipine

AngII:

Angiotensin II

AngI:

Angiotensin I

Ang(1-7):

Angiotensin-(1-7)

AngIV:

Angiotensin IV

ARB:

AT1 receptor blocker

AT1 receptor:

Angiotensin II type 1 receptor

BBB:

Blood-brain barrier

bw:

Body weight

C-21:

Compound 21

CAND:

Candesartan

CD:

Cafeteria diet

DAPI:

(4′,6-Diamidino-2-phenylindole) dihydrochloride

GLUT:

Glucose transporter

HPA axis:

Hypothalamic-pituitary-adrenal axis

IRS-1:

Insulin receptor substrate-1

KRB:

Krebs-Ringer buffer

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

OGTT:

Oral glucose tolerance test

PIC:

Protease inhibitor cocktail

PI3K:

Phosphatidylinositol-3-kinase

RAM:

Ramipril

RAS:

Renin-angiotensin system

RIA:

Radioimmune assay

SD:

Sprague Dawley rats

TB:

TRIS buffer

TEL:

Telmisartan

T2DM:

Type 2 diabetes mellitus

TRIS:

Tris(hydroxymethyl)aminomethane

References

  • Banks WA, DiPalma CR, Farrell CL (1999) Impaired transport of leptin across the blood-brain barrier in obesity. Peptides 20:1341–1345

    Article  CAS  PubMed  Google Scholar 

  • Beck IT (1973) The role of pancreatic enzymes in digestion. Am J Clin Nutr 26:311–325

    CAS  PubMed  Google Scholar 

  • Berglund ED, Vianna CR, Donato J Jr, Kim MH, Chuang JC, Lee CE, Lauzon DA, Lin P, Brule LJ, Scott MM, Coppari R, Elmquist JK (2012) Direct leptin action on POMC neurons regulates glucose homeostasis and hepatic insulin sensitivity in mice. J Clin Invest 122:1000–1009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boulay G, Gallo-Payet N, Guillemette G (1990) Implication of phospholipase C in the steroidogenic action of angiotensin II. Eur J Pharmacol 189:267–275

    Article  CAS  PubMed  Google Scholar 

  • Brilla CG, Scheer C, Rupp H (1998) Angiotensin II and intracellular calcium of adult cardiac fibroblasts. J Mol Cell Cardiol 30:1237–1246

    Article  CAS  PubMed  Google Scholar 

  • Campbell JE, Drucker DJ (2015) Islet alpha cells and glucagon—critical regulators of energy homeostasis. Nat Rev Endocrinol 11:329–338

    Article  CAS  PubMed  Google Scholar 

  • Carlsson PO (2001) The renin-angiotensin system in the endocrine pancreas. JOP 2:26–32

    CAS  PubMed  Google Scholar 

  • Carter JD, Dula SB, Corbin KL, Wu R, Nunemaker CS (2009) A practical guide to rodent islet isolation and assessment. Biol Proced Online 11:3–31

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Catt KJ, Cain MD, Zimmet PZ, Cran E (1969) Blood angiotensin II levels of normal and hypertensive subjects. Br Med J 1:819–821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cavadas C, Grand D, Mosimann F, Cotrim MD, Fontes Ribeiro CA, Brunner HR, Grouzmann E (2003) Angiotensin II mediates catecholamine and neuropeptide Y secretion in human adrenal chromaffin cells through the AT1 receptor. Regul Pept 111:61–65

    Article  CAS  PubMed  Google Scholar 

  • Chappell MC, Millsted A, Diz DI, Brosnihan KB, Ferrario CM (1991) Evidence for an intrinsic angiotensin system in the canine pancreas. J Hypertens 9:751–759

    Article  CAS  PubMed  Google Scholar 

  • Chu KY, Lau T, Carlsson PO, Leung PS (2006) Angiotensin II type 1 receptor blockade improves beta-cell function and glucose tolerance in a mouse model of type 2 diabetes. Diabetes 55:367–374

    Article  CAS  PubMed  Google Scholar 

  • Dunning BE, Moltz JH, Fawcett CP (1984) Actions of neurohypophysial peptides on pancreatic hormone release. Am J Phys 246:E108–E114

    CAS  Google Scholar 

  • Elliott WJ, Meyer PM (2007) Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis. Lancet 369:201–207

    Article  CAS  PubMed  Google Scholar 

  • Fehmann HC, Peiser C, Bode HP, Stamm M, Staats P, Hedetoft C, Lang RE, Goke B (1997) Leptin: a potent inhibitor of insulin secretion. Peptides 18:1267–1273

    Article  CAS  PubMed  Google Scholar 

  • Frantz ED, Crespo-Mascarenhas C, Barreto-Vianna AR, Aguila MB, Mandarim-de-Lacerda CA (2013) Renin-angiotensin system blockers protect pancreatic islets against diet-induced obesity and insulin resistance in mice. PLoS One 8:e67192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fujikawa T, Chuang JC, Sakata I, Ramadori G, Coppari R (2010) Leptin therapy improves insulin-deficient type 1 diabetes by CNS-dependent mechanisms in mice. Proc Natl Acad Sci U S A 107:17391–17396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • German JP, Thaler JP, Wisse BE, Oh I, Sarruf DA, Matsen ME, Fischer JD, Taborsky GJ Jr, Schwartz MW, Morton GJ (2011) Leptin activates a novel CNS mechanism for insulin-independent normalization of severe diabetic hyperglycemia. Endocrinology 152:394–404

    Article  CAS  PubMed  Google Scholar 

  • Ghiani BU, Masini MA (1995) Angiotensin II binding sites in the rat pancreas and their modulation after sodium loading and depletion. Comp Biochem Physiol A Physiol 111:439–444

    Article  CAS  PubMed  Google Scholar 

  • Giugliano D, Torella R, D’Onofrio F (1981) Prostaglandins and the alpha-cell. Prostaglandins Med 6:283–297

    Article  CAS  PubMed  Google Scholar 

  • Grankvist K, Lernmark A, Taljedal IB (1979) Trypan blue as a marker of plasma membrane permeability in alloxan-treated mouse islet cells. J Endocrinol Investig 2:139–145

    Article  CAS  Google Scholar 

  • Gromada J, Franklin I, Wollheim CB (2007) Alpha-cells of the endocrine pancreas: 35 years of research but the enigma remains. Endocr Rev 28:84–116

    Article  CAS  Google Scholar 

  • Gylfe E, Gilon P (2014) Glucose regulation of glucagon secretion. Diabetes Res Clin Pract 103:1–10

    Article  CAS  PubMed  Google Scholar 

  • Hamaguchi K, Leiter EH (1990) Comparison of cytokine effects on mouse pancreatic alpha-cell and beta-cell lines. Viability, secretory function, and MHC antigen expression. Diabetes 39:415–425

    Article  CAS  PubMed  Google Scholar 

  • Hupe-Sodmann K, Goke R, Goke B, Thole HH, Zimmermann B, Voigt K, McGregor GP (1997) Endoproteolysis of glucagon-like peptide (GLP)-1 (7-36) amide by ectopeptidases in RINm5F cells. Peptides 18:625–632

    Article  CAS  PubMed  Google Scholar 

  • Jaiswal N, Diz DI, Tallant EA, Khosla MC, Ferrario CM (1991a) Characterization of angiotensin receptors mediating prostaglandin synthesis in C6 glioma cells. Am J Phys 260:R1000–R1006

    CAS  Google Scholar 

  • Jaiswal N, Tallant EA, Diz DI, Khosla MC, Ferrario CM (1991b) Subtype 2 angiotensin receptors mediate prostaglandin synthesis in human astrocytes. Hypertension 17:1115–1120

    Article  CAS  PubMed  Google Scholar 

  • Kelly KL, Laychock SG (1981) Prostaglandin synthesis and metabolism in isolated pancreatic islets of the rat. Prostaglandins 21:759–769

    Article  CAS  PubMed  Google Scholar 

  • Kintscher U, Foryst-Ludwig A, Unger T (2008) Inhibiting angiotensin type 1 receptors as a target for diabetes. Expert Opin Ther Targets 12:1257–1263

    Article  CAS  PubMed  Google Scholar 

  • Lacy PE, Kostianovsky M (1967) Method for the isolation of intact islets of Langerhans from the rat pancreas. Diabetes 16:35–39

    Article  CAS  PubMed  Google Scholar 

  • Latif ZA, Noel J, Alejandro R (1988) A simple method of staining fresh and cultured islets. Transplantation 45:827–830

    Article  CAS  PubMed  Google Scholar 

  • Lau T, Carlsson PO, Leung PS (2004) Evidence for a local angiotensin-generating system and dose-dependent inhibition of glucose-stimulated insulin release by angiotensin II in isolated pancreatic islets. Diabetologia 47:240–248

    Article  CAS  PubMed  Google Scholar 

  • Leclercq-Meyer V, Malaisse WJ (1998) Failure of human and mouse leptin to affect insulin, glucagon and somatostatin secretion by the perfused rat pancreas at physiological glucose concentration. Mol Cell Endocrinol 141:111–118

    Article  CAS  PubMed  Google Scholar 

  • Leclercq-Meyer V, Considine RV, Sener A, Malaisse WJ (1996) Do leptin receptors play a functional role in the endocrine pancreas? Biochem Biophys Res Commun 229:794–798

    Article  CAS  PubMed  Google Scholar 

  • Leung KK, Leung PS (2008) Effects of hyperglycemia on angiotensin II receptor type 1 expression and insulin secretion in an INS-1E pancreatic beta-cell line. JOP 9:290–299

    PubMed  Google Scholar 

  • Marroqui L, Vieira E, Gonzalez A, Nadal A, Quesada I (2011) Leptin downregulates expression of the gene encoding glucagon in alphaTC1-9 cells and mouse islets. Diabetologia 54:843–851

    Article  CAS  PubMed  Google Scholar 

  • Miesel A, Müller H, Thermann M, Heidbreder M, Dominiak P, Raasch W (2010) Overfeeding-induced obesity in spontaneously hypertensive rats: an animal model of the human metabolic syndrome. Ann Nutr Metab 56:127–142

    Article  CAS  PubMed  Google Scholar 

  • Miesel A, Müller-Fielitz H, Jöhren O, Vogt FM, Raasch W (2012) Double blockade of angiotensin II (AT(1))-receptors and ACE does not improve weight gain and glucose homeostasis better than single-drug treatments in obese rats. Br J Pharmacol 165:2721–2735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Müller H, Schweitzer N, Jöhren O, Dominiak P, Raasch W (2007) Angiotensin II stimulates the reactivity of the pituitary-adrenal axis in leptin-resistant Zucker rats, thereby influencing the glucose utilization. Am J Physiol Endocrinol Metab 293:E802–E810

    Article  PubMed  Google Scholar 

  • Müller-Fielitz H, Markert A, Wittmershaus C, Pahlke F, Jöhren O, Raasch W (2011) Weight loss and hypophagia after high-dose AT1-blockade is only observed after high dosing and depends on regular leptin signalling but not blood pressure. Naunyn Schmiedebergs Arch Pharmacol 383:373–384

    Article  PubMed  Google Scholar 

  • Müller-Fielitz H, Landolt J, Heidbreder M, Werth S, Vogt FM, Jöhren O, Raasch W (2012) Improved insulin sensitivity after long-term treatment with AT1 blockers is not associated with PPARgamma target gene regulation. Endocrinology 153:1103–1115

    Article  PubMed  Google Scholar 

  • Müller-Fielitz H, Hubel N, Mildner M, Vogt FM, Barkhausen J, Raasch W (2014) Chronic blockade of angiotensin AT(1) receptors improves cardinal symptoms of metabolic syndrome in diet-induced obesity in rats. Br J Pharmacol 171:746–760

    Article  PubMed  PubMed Central  Google Scholar 

  • Müller-Fielitz H, Lau M, Geissler C, Werner L, Piehl M, Raasch W (2015) Preventing leptin resistance by blocking angiotensin II AT1 receptors in diet-induced obese rats. Br J Pharmacol 172:857–868

    Article  PubMed  Google Scholar 

  • O’Dowd JF (2009) The isolation and purification of rodent pancreatic islets of Langerhans. Methods Mol Biol 560:37–42

    Article  PubMed  Google Scholar 

  • Padfield PL, Morton JJ (1977) Effects of angiotensin II on arginine-vasopressin in physiological and pathological situations in man. J Endocrinol 74:251–259

    Article  CAS  PubMed  Google Scholar 

  • Paul M, Poyan MA, Kreutz R (2006) Physiology of local renin-angiotensin systems. Physiol Rev 86:747–803

    Article  CAS  PubMed  Google Scholar 

  • Pavlatou MG, Mastorakos G, Lekakis I, Liatis S, Vamvakou G, Zoumakis E, Papassotiriou I, Rabavilas AD, Katsilambros N, Chrousos GP (2008) Chronic administration of an angiotensin II receptor antagonist resets the hypothalamic-pituitary-adrenal (HPA) axis and improves the affect of patients with diabetes mellitus type 2: preliminary results. Stress 11:62–72

    Article  CAS  PubMed  Google Scholar 

  • Pek S, Tai TY, Elster A (1978) Stimulatory effects of prostaglandins E-1, E-2, and F-2-alpha on glucagon and insulin release in vitro. Diabetes 27:801–809

    Article  CAS  PubMed  Google Scholar 

  • Perkins JM, Davis SN (2008) The renin-angiotensin-aldosterone system: a pivotal role in insulin sensitivity and glycemic control. Curr Opin Endocrinol Diabetes Obes 15:147–152

    Article  CAS  PubMed  Google Scholar 

  • Phillips MI (1987) Functions of angiotensin in the central nervous system. Annu Rev Physiol 49:413–435

    Article  CAS  PubMed  Google Scholar 

  • Powers AC, Efrat S, Mojsov S, Spector D, Habener JF, Hanahan D (1990) Proglucagon processing similar to normal islets in pancreatic alpha-like cell line derived from transgenic mouse tumor. Diabetes 39:406–414

    Article  CAS  PubMed  Google Scholar 

  • Raasch W, Wittmershaus C, Dendorfer A, Voges I, Pahlke F, Dodt C, Dominiak P, Jöhren O (2006) Angiotensin II inhibition reduces stress sensitivity of hypothalamo-pituitary-adrenal axis in spontaneously hypertensive rats. Endocrinology 147:3539–3546

    Article  CAS  PubMed  Google Scholar 

  • Ribeiro-Oliveira A Jr, Nogueira AI, Pereira RM, Boas WW, Dos Santos RA, Simoes e Silva AC (2008) The renin-angiotensin system and diabetes: an update. Vasc Health Risk Manag 4:787–803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Satoh H, Matsukura K, Yamada R, Satoh S (1981) Influence of angiotensins (I, II & III) on prostaglandin production by minced rat renal medulla. Prostaglandins 21:973–984

    Article  CAS  PubMed  Google Scholar 

  • Scharschmidt LA, Dunn MJ (1983) Prostaglandin synthesis by rat glomerular mesangial cells in culture. Effects of angiotensin II and arginine vasopressin. J Clin Invest 71:1756–1764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scheen AJ (2004a) Renin-angiotensin system inhibition prevents type 2 diabetes mellitus. Part 1. A meta-analysis of randomised clinical trials. Diabetes Metab 30:487–496

    Article  CAS  PubMed  Google Scholar 

  • Scheen AJ (2004b) Renin-angiotensin system inhibition prevents type 2 diabetes mellitus. Part 2. Overview of physiological and biochemical mechanisms. Diabetes Metab 30:498–505

    Article  CAS  PubMed  Google Scholar 

  • Schuchard J, Winkler M, Stölting I, Schuster F, Vogt FM, Barkhausen J, Thorns C, Santos RA, Bader M, Raasch W (2015) Prevention of weight gain after AT1 receptor blockade in diet-induced rat obesity is at least partially related to an angiotensin(1-7)/Mas-dependent mechanism. Br J Pharmacol 172:3764–3778

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shimizu H, Tsuchiya T, Ohtani K, Shimomura K, Oh I, Ariyama Y, Okada S, Kishi M, Mori M (2011) Glucagon plays an important role in the modification of insulin secretion by leptin. Islets 3:150–154

    Article  PubMed  Google Scholar 

  • Steckelings U, Lebrun C, Qadri F, Veltmar A, Unger T (1992) Role of brain angiotensin in cardiovascular regulation. J Cardiovasc Pharmacol 19(Suppl 6):S72–S79

    Article  CAS  PubMed  Google Scholar 

  • Steckelings UM, Larhed M, Hallberg A, Widdop RE, Jones ES, Wallinder C, Namsolleck P, Dahlof B, Unger T (2011) Non-peptide AT2-receptor agonists. Curr Opin Pharmacol 11:187–192

    Article  CAS  PubMed  Google Scholar 

  • Tuduri E, Marroqui L, Soriano S, Ropero AB, Batista TM, Piquer S, Lopez-Boado MA, Carneiro EM, Gomis R, Nadal A, Quesada I (2009) Inhibitory effects of leptin on pancreatic alpha-cell function. Diabetes 58:1616–1624

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Unger T, Dahlof B (2010) Compound 21, the first orally active, selective agonist of the angiotensin type 2 receptor (AT2): implications for AT2 receptor research and therapeutic potential. J Renin-Angiotensin-Aldosterone Syst 11:75–77

    Article  CAS  PubMed  Google Scholar 

  • van der Zijl NJ, Moors CC, Goossens GH, Blaak EE, Diamant M (2012) Does interference with the renin-angiotensin system protect against diabetes? Evidence and mechanisms. Diabetes Obes Metab 14:586–595

    Article  PubMed  Google Scholar 

  • Veltmar A, Culman J, Qadri F, Rascher W, Unger T (1992) Involvement of adrenergic and angiotensinergic receptors in the paraventricular nucleus in the angiotensin II-induced vasopressin release. J Pharmacol Exp Ther 263:1253–1260

    CAS  PubMed  Google Scholar 

  • Vieira E, Liu YJ, Gylfe E (2004) Involvement of alpha1 and beta-adrenoceptors in adrenaline stimulation of the glucagon-secreting mouse alpha-cell. Naunyn Schmiedebergs Arch Pharmacol 369:179–183

    Article  CAS  PubMed  Google Scholar 

  • Wan Y, Wallinder C, Plouffe B, Beaudry H, Mahalingam AK, Wu X, Johansson B, Holm M, Botoros M, Karlen A, Pettersson A, Nyberg F, Fandriks L, Gallo-Payet N, Hallberg A, Alterman M (2004) Design, synthesis, and biological evaluation of the first selective nonpeptide AT2 receptor agonist. J Med Chem 47:5995–6008

    Article  CAS  PubMed  Google Scholar 

  • Whitcomb DC, Lowe ME (2007) Human pancreatic digestive enzymes. Dig Dis Sci 52:1–17

    Article  CAS  PubMed  Google Scholar 

  • Winkler M, Schuchard J, Stölting I, Vogt FM, Barkhausen J, Thorns C, Bader M, Raasch W (2016) The brain renin-angiotensin system plays a crucial role in regulating body weight in diet-induced rat obesity. Br J Pharmacol 173:1602–1617

    Article  CAS  PubMed  Google Scholar 

  • Zhang Z, Liu C, Gan Z, Wang X, Yi Q, Liu Y, Wang Y, Lu B, Du H, Shao J, Wang J (2013) Improved glucose-stimulated insulin secretion by selective intraislet inhibition of angiotensin II type 1 receptor expression in isolated islets of db/db mice. Int J Endocrinol 2013:319586

    PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors gratefully acknowledge Martin Michel (Boehringer Ingelheim Pharmaceuticals, Inc., Ingelheim, Germany) for his critical reading of the manuscript and his helpful comments and Sherryl Sundell for improving the English style.

Author contributions

MM, HMF, IS, OJ, MS and WR performed the research; WR, MM and HMF designed the research study; MM, HMF and WR analysed the data, and WR and MM wrote the paper.

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Authors and Affiliations

  1. Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany

    Martin Mildner, Helge Müller-Fielitz, Ines Stölting, Olaf Jöhren & Walter Raasch

  2. DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Lübeck, Germany

    Helge Müller-Fielitz & Walter Raasch

  3. Center of Brain, Behavior and Metabolism (CBBM), Lübeck, Germany

    Helge Müller-Fielitz, Olaf Jöhren & Walter Raasch

  4. Department of Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark

    Muscha Steckelings

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  1. Martin Mildner
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  2. Helge Müller-Fielitz
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  3. Ines Stölting
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Correspondence to Walter Raasch.

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This study was funded by the Excellent Funding of the Medical Section of the University of Lübeck. AstraZeneca (Wedel, Germany) and Boehringer Ingelheim Pharmaceuticals, Inc. (Ingelheim, Germany) supported the study by providing study medication.

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The authors declare that they have no conflict of interest.

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Mildner, M., Müller-Fielitz, H., Stölting, I. et al. Glucagon increase after chronic AT1 blockade is more likely related to an indirect leptin-dependent than to a pancreatic α-cell-dependent mechanism. Naunyn-Schmiedeberg's Arch Pharmacol 390, 505–518 (2017). https://doi.org/10.1007/s00210-017-1346-7

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