History of insulin

Quianzon, Celeste C.L.; Cheikh, Issam E.

doi:10.3402/jchimp.v2i2.18701

Cited by 129 publications

(112 citation statements)

References 9 publications

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“…Despite these early observations that inferred an important role for the central nervous system (CNS) in the control of glucose homeostasis, the discovery of insulin by Banting and Best in 1921 along with its ability to markedly reduce blood glucose overshadowed and diverted attention away from the role of the brain . Indeed, much of the research that followed the characterisation of insulin, particularly during the 1960s to 1980s, ultimately type‐casted insulin so that it was understood to act solely through peripheral tissues to control glucose metabolism, ignoring any involvement of the brain . Despite the IR and its signalling intermediates being widely expressed within mammalian and human brains, this peripheral‐centric view was reaffirmed by early observations indicating that the majority of glucose transport into neurones occurred independently of insulin; it is now known that, in a subset of hypothalamic neurones, glucose uptake may occur via the insulin‐dependent glucose transporter GLUT4 .…”

Section: Insulin and The Brainmentioning

confidence: 99%

“…2,3 Indeed, much of the research that followed the characterisation of insulin, particularly during the 1960s to 1980s, ultimately type-casted insulin so that it was understood to act solely through peripheral tissues to control glucose metabolism, ignoring any involvement of the brain. 4 Despite the IR and its signalling intermediates being widely expressed within mammalian and human brains, [5][6][7][8][9] this peripheral-centric view was reaffirmed by early observations indicating that the majority of glucose transport into neurones occurred independently of insulin; it is now known that, in a subset of hypothalamic neurones, glucose uptake may occur via the insulin-dependent glucose transporter GLUT4. 10,11 Nonetheless, evidence emanating from decades of research now supports varied neuromodulatory roles for insulin signalling in the CNS.…”

Section: Insulin and The Brainmentioning

confidence: 99%

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Insulin action in the brain: Roles in energy and glucose homeostasis

Dodd

Tiganis

2017

J Neuroendocrinology

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A growing body of evidence from research in rodents and humans has identified insulin as an important neuoregulatory peptide in the brain, where it coordinates diverse aspects of energy balance and peripheral glucose homeostasis. This review discusses where and how insulin interacts within the brain and evaluates the physiological and pathophysiological consequences of central insulin signalling in metabolism, obesity and type 2 diabetes. K E Y W O R D SAgRP, energy homeostasis, glucose homeostasis, hypothalamus, insulin, POMC | INTRODUCTIONInsulin targets peripheral tissues, including skeletal muscle, adipose tissue, where it promotes glucose uptake from the blood, and the liver, where it inhibits gluconeogenesis and glycogenolysis and promotes glycogen synthesis to coordinately repress hepatic glucose production.In this way, insulin prevents postprandial hyperglycaemia and maintains euglycaemia. In addition to these peripheral targets, insulin also signals in the brain, although the physiological significance of this interaction has only recently started to emerge. Research over the past two decades has provided compelling evidence that central insulin signalling plays pivotal roles in many aspects of energy and glucose homeostasis (Figure 1). Given the epidemics of obesity and type 2 diabetes (T2D) in developed and increasingly developing countries, there is a pressing need to fully understand the mechanisms by which the body coordinates energy and glucose homeostasis. A key hallmark of obesity and T2D is insulin resistance, where defective insulin signalling downstream of the insulin receptor (IR) renders the peripheral target tissues of insulin insensitive to the action of insulin. What is becoming increasingly apparent is that neurones in the brain also become resistant to insulin; however the relative contributions of central insulin resistance to the development of obesity and T2D remain poorly understood.This review discusses the role of insulin in the brain with respect to coordinating glucose metabolism with energy expenditure. In particular, we discuss our understanding of the locations and mechanisms by which insulin elicits its effects in the brain, its influence on glucose metabolism and energy expenditure, and the potential contributions of central insulin resistancein the development of obesity and the metabolic syndrome.

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Section: Insulin and The Brainmentioning

confidence: 99%

Section: Insulin and The Brainmentioning

confidence: 99%

Insulin action in the brain: Roles in energy and glucose homeostasis

Dodd

Tiganis

2017

J Neuroendocrinology

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“…Diabetes was responsible for 10.8 % of health expenditures (at least $548 billion) in 2013; expected to hit $678 billion in 2035, which demonstrates the global relevance and the requirement of efficient treatment (Abdullah et al 2014;Atkinson et al 2014;International Diabetes Federation 2013;Hu 2011). Diabetes mellitus was first described more than 2,500 years ago in the Ebers papyrus and first successfully treated by injection of insulin in 1922 to Leonard Thompson a 14-year old boy who survived some more years under insulin therapy (Yaturu 2013;Quianzon and Cheikh 2012a;Rosenfeld 2002). At the beginning, insulin was exclusively administered by intramuscular injection, but for avoidance of patient traumatization subcutaneous application was rapidly established.…”

Section: Introductionmentioning

confidence: 99%

Aerosolized GLP-1 for Treatment of Diabetes Mellitus and Irritable Bowel Syndrome

Siekmeier

Hofmann²,

Scheuch

et al. 2014

Advances in Experimental Medicine and Biology

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Diabetes is a global burden and the prevalence of the disease, in particular diabetes mellitus type 2 is rapidly increasing worldwide. After introduction of insulin into clinical therapy about 90 years ago a major number of pharmaceuticals has been developed for treatment of diabetes mellitus type 2. One of these, the incretin glucagon-like peptide 1 (GLP-1), like insulin, needs subcutaneous administration causing inconvenience to patients. However, administration of GLP-1 plays also a role for treatment of irritable bowel syndrome (IBS). To improve patient convenience inhaled insulin (Exubera(®)) was developed and approved but failed market acceptance some years ago. Recently, another inhalative insulin (Afrezza(®)) received market approval and GLP-1 may serve as another candidate drug for inhalative administration. This review analyzes the current literature investigating alternative administration of GLP-1 and GLP-1 analogs focusing on inhalation. Several formulations for inhalative administration of GLP-1 and analogs were investigated in animal studies, whereas there are only few clinical data. However, feasibility of GLP-1 inhalation has been shown and should be further investigated as such type of drug administration may serve for improvement of therapy in patients with diabetes mellitus or irritable bowel syndrome.

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“…Insulin is a 5700 molecular weight protein that has been a leading candidate for noninvasive delivery since its initial use by injection in 1921 for the management of diabetes. 1,2 However, noninvasive delivery of insulin has a history of failure despite much research effort, particularly with oral and nasal approaches, because the nasal and gastrointestinal epithelia are functionally impermeable to insulin. 3,4 The lungs, which are naturally permeable to some proteins, have become a target for insulin delivery.…”

mentioning

confidence: 99%