On 2014 Jun 02, Gaetano Santulli commented:

In this article, Ribeiro and colleagues report that β2-adrenergic receptor (β2AR) knockout (KO) mice exhibit altered glucose homeostasis (1). Albeit surprisingly not reported by the Authors, the notion that deletion of the β2AR has profound effects on glucose metabolism is a consolidated acquisition. Indeed, we recently demonstrated that the deletion of β2AR impairs insulin release ultimately leading to glucose intolerance (2). Previously, Muzzin and colleagues had found that the lack of βARs associates with glucose intolerance (3). Findings from several groups support such a molecular mechanism (4-6). Equally important, in the clinical scenario, a mechanistic role for β2AR in the regulation of insulin secretion had been also suggested by the evidence of a decreased number of β2AR in type I diabetes mellitus patients (7-9). Nevertheless, the Authors fail to discuss previous relevant literature describing the alterations in glucose metabolism observed in β2AR KO mice and do not accurately circumstantiate their findings. In fact, they state that “available animal models indicate only a minor metabolic role” for β2AR. Moreover, despite insulin signaling has been shown to play a key role in the regulation of thermogenesis, as recently verified by Ron Kahn and colleagues (10), the Authors just show baseline serum insulin levels without providing any measurement (not even in isolated islets) following glucose challenge. We believe that for the sake of scientific appropriateness the Readers will appreciate a clarification by the Authors and the Editors, in particular regarding the fact that pertinent literature in the field has been overlooked.

References:

1. Fernandes GW, Ueta CB, Fonseca TL, Gouveia CH, Lancellotti CL, Brum PC, Christoffolete MA, Bianco AC, Ribeiro MO 2014 Inactivation of the adrenergic receptor beta2 disrupts glucose homeostasis in mice. The Journal of endocrinology 221:381-390
2. Santulli G, Lombardi A, Sorriento D, Anastasio A, Del Giudice C, Formisano P, Beguinot F, Trimarco B, Miele C, Iaccarino G 2012 Age-related impairment in insulin release: the essential role of beta(2)-adrenergic receptor. Diabetes 61:692-701
3. Asensio C, Jimenez M, Kuhne F, Rohner-Jeanrenaud F, Muzzin P 2005 The lack of beta-adrenoceptors results in enhanced insulin sensitivity in mice exhibiting increased adiposity and glucose intolerance. Diabetes 54:3490-3495
4. Panagiotidis G, Stenstrom A, Lundquist I 1993 Influence of beta 2-adrenoceptor stimulation and glucose on islet monoamine oxidase activity and insulin secretory response in the mouse. Pancreas 8:368-374
5. Ahren B, Jarhult J, Lundquist I 1981 Insulin secretion induced by glucose and by stimulation of beta 2 -adrenoceptors in the rat. Different sensitivity to somatostatin. Acta physiologica Scandinavica 112:421-426
6. Loubatieres A, Mariani MM, Sorel G, Savi L 1971 The action of beta-adrenergic blocking and stimulating agents on insulin secretion. Characterization of the type of beta receptor. Diabetologia 7:127-132
7. Schwab KO, Bartels H, Martin C, Leichtenschlag EM 1993 Decreased beta 2-adrenoceptor density and decreased isoproterenol induced c-AMP increase in juvenile type I diabetes mellitus: an additional cause of severe hypoglycaemia in childhood diabetes? European journal of pediatrics 152:797-801
8. Noji T, Tashiro M, Yagi H, Nagashima K, Suzuki S, Kuroume T 1986 Adaptive regulation of beta-adrenergic receptors in children with insulin dependent diabetes mellitus. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 18:604-606
9. Santulli G, Iaccarino G 2013 Pinpointing beta adrenergic receptor in ageing pathophysiology: victim or executioner? Evidence from crime scenes. Immunity & ageing : I & A 10:10
10. Boucher J, Mori MA, Lee KY, Smyth G, Liew CW, Macotela Y, Rourk M, Bluher M, Russell SJ, Kahn CR 2012 Impaired thermogenesis and adipose tissue development in mice with fat-specific disruption of insulin and IGF-1 signalling. Nature communications 3:902

Gaetano Santulli MD, PhD (1,2) and Guido Iaccarino MD, PhD (3,4)

From the (1) College of Physicians & Surgeons, Columbia University Medical Center, New York, NY, USA; (2) Departments of Translational Medical Sciences and Advanced Biomedical Sciences, “Federico II” University, Naples Italy; (3) Department of Medicine and Surgery, University of Salerno, Salerno, Italy; (4) IRCCS Multimedica, Milan, Italy.

On 2014 Jun 02, Gaetano Santulli commented:

In this article, Ribeiro and colleagues report that β2-adrenergic receptor (β2AR) knockout (KO) mice exhibit altered glucose homeostasis (1). Albeit surprisingly not reported by the Authors, the notion that deletion of the β2AR has profound effects on glucose metabolism is a consolidated acquisition. Indeed, we recently demonstrated that the deletion of β2AR impairs insulin release ultimately leading to glucose intolerance (2). Previously, Muzzin and colleagues had found that the lack of βARs associates with glucose intolerance (3). Findings from several groups support such a molecular mechanism (4-6). Equally important, in the clinical scenario, a mechanistic role for β2AR in the regulation of insulin secretion had been also suggested by the evidence of a decreased number of β2AR in type I diabetes mellitus patients (7-9). Nevertheless, the Authors fail to discuss previous relevant literature describing the alterations in glucose metabolism observed in β2AR KO mice and do not accurately circumstantiate their findings. In fact, they state that “available animal models indicate only a minor metabolic role” for β2AR. Moreover, despite insulin signaling has been shown to play a key role in the regulation of thermogenesis, as recently verified by Ron Kahn and colleagues (10), the Authors just show baseline serum insulin levels without providing any measurement (not even in isolated islets) following glucose challenge. We believe that for the sake of scientific appropriateness the Readers will appreciate a clarification by the Authors and the Editors, in particular regarding the fact that pertinent literature in the field has been overlooked.

References:

1. Fernandes GW, Ueta CB, Fonseca TL, Gouveia CH, Lancellotti CL, Brum PC, Christoffolete MA, Bianco AC, Ribeiro MO 2014 Inactivation of the adrenergic receptor beta2 disrupts glucose homeostasis in mice. The Journal of endocrinology 221:381-390
2. Santulli G, Lombardi A, Sorriento D, Anastasio A, Del Giudice C, Formisano P, Beguinot F, Trimarco B, Miele C, Iaccarino G 2012 Age-related impairment in insulin release: the essential role of beta(2)-adrenergic receptor. Diabetes 61:692-701
3. Asensio C, Jimenez M, Kuhne F, Rohner-Jeanrenaud F, Muzzin P 2005 The lack of beta-adrenoceptors results in enhanced insulin sensitivity in mice exhibiting increased adiposity and glucose intolerance. Diabetes 54:3490-3495
4. Panagiotidis G, Stenstrom A, Lundquist I 1993 Influence of beta 2-adrenoceptor stimulation and glucose on islet monoamine oxidase activity and insulin secretory response in the mouse. Pancreas 8:368-374
5. Ahren B, Jarhult J, Lundquist I 1981 Insulin secretion induced by glucose and by stimulation of beta 2 -adrenoceptors in the rat. Different sensitivity to somatostatin. Acta physiologica Scandinavica 112:421-426
6. Loubatieres A, Mariani MM, Sorel G, Savi L 1971 The action of beta-adrenergic blocking and stimulating agents on insulin secretion. Characterization of the type of beta receptor. Diabetologia 7:127-132
7. Schwab KO, Bartels H, Martin C, Leichtenschlag EM 1993 Decreased beta 2-adrenoceptor density and decreased isoproterenol induced c-AMP increase in juvenile type I diabetes mellitus: an additional cause of severe hypoglycaemia in childhood diabetes? European journal of pediatrics 152:797-801
8. Noji T, Tashiro M, Yagi H, Nagashima K, Suzuki S, Kuroume T 1986 Adaptive regulation of beta-adrenergic receptors in children with insulin dependent diabetes mellitus. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 18:604-606
9. Santulli G, Iaccarino G 2013 Pinpointing beta adrenergic receptor in ageing pathophysiology: victim or executioner? Evidence from crime scenes. Immunity & ageing : I & A 10:10
10. Boucher J, Mori MA, Lee KY, Smyth G, Liew CW, Macotela Y, Rourk M, Bluher M, Russell SJ, Kahn CR 2012 Impaired thermogenesis and adipose tissue development in mice with fat-specific disruption of insulin and IGF-1 signalling. Nature communications 3:902

Gaetano Santulli MD, PhD (1,2) and Guido Iaccarino MD, PhD (3,4)

From the (1) College of Physicians & Surgeons, Columbia University Medical Center, New York, NY, USA; (2) Departments of Translational Medical Sciences and Advanced Biomedical Sciences, “Federico II” University, Naples Italy; (3) Department of Medicine and Surgery, University of Salerno, Salerno, Italy; (4) IRCCS Multimedica, Milan, Italy.