GLP-1, abreviatura de péptido 1 similar al glucagón, es una hormona peptídica corta y natural de solo 30 a 31 aminoácidos de longitud. Su función fisiológica principal es reducir los niveles de azúcar en sangre mejorando naturalmente la secreción de insulina. También desempeña un papel en la protección de las reservas de insulina de las células beta al promover la transcripción del gen de la insulina y se ha relacionado con efectos neurotróficos en el cerebro y el sistema nervioso central. En el sistema gastrointestinal, se ha demostrado que el GLP-1 disminuye significativamente el apetito al retrasar el vaciado gástrico y reducir la motilidad intestinal. La investigación preliminar ha demostrado también los efectos del GLP-1 en el corazón, la grasa, los músculos, los huesos, el hígado, los pulmones y los riñones.

El enfoque principal de la investigación sobre GLP-1 ha sido el ámbito del tratamiento/prevención de la diabetes, así como la supresión del apetito. La investigación secundaria se centra en los posibles beneficios cardiovasculares del péptido. Las investigaciones más recientes, y por tanto menos sólidas, se centran en la capacidad del GLP-1 para prevenir enfermedades neurodegenerativas. Aunque esta última área de investigación es más nueva, también es el área de rápido crecimiento del estudio del GLP-1 ahora que se ha revelado que el péptido retarda o previene la acumulación de placas beta amiloides en el contexto de la enfermedad de Alzheimer.

Fuente:PubChemSecuencia:HXEGTFTSDVSSYLEGQAAK-OH.diácido estérico-EFIAWLVRGRGFórmula molecular:C187H291N45O59Peso molecular: 4113,64 g/molPubChem CID: 56843331Número CAS: 910463-68-2Sinónimos:Semaglutida, Oxempic, Rybelsus, NN9535

El efecto incretina del GLP-1

Perhaps the most important effect that GLP-1 has, according to Dr. Holst, is referred to as the “incretin effect.” Incretins are a group of metabolic hormones, released by the GI tract, that cause a decrease in blood glucose (sugar) levels. GLP-1 has been shown to be one of the two most important hormones (the other being GIP) to stimulate the incretin effect in rodent models. Though GIP circulates at levels roughly 10 times higher than that of GLP-1, there is evidence that GLP-1 is the more potent of the two molecules, particularly when levels of blood glucose are quite high. A GLP-1 receptor has been identified on the surface of pancreatic beta cells, making it clear that GLP-1 directly stimulates the exocytosis of insulin from the pancreas. When combined with sulfonylurea drugs, GLP-1 has been shown to boost insulin secretion enough to cause mild hypoglycemia in up to 40% of subjects^[1]. Por supuesto, el aumento de la secreción de insulina se asocia con una serie de efectos tróficos que incluyen un aumento de la síntesis de proteínas, una reducción en la degradación de las proteínas y una mayor absorción de aminoácidos por el músculo esquelético.

GLP-1 y protección de células beta

La investigación en modelos animales sugiere que el GLP-1 puede estimular el crecimiento y la proliferación de células beta pancreáticas y que puede estimular la diferenciación de nuevas células beta que forman progenitores en el epitelio del conducto pancreático. La investigación también ha demostrado que el GLP-1 inhibe la apoptosis de las células beta.^[1]. Taken in sum, these effects tip the usual balance of beta cell growth and death toward growth, suggesting that the peptide may be useful in treating diabetes and in protecting the pancreas against insult that harms beta cells. In one particularly compelling trial, GLP-1 was shown to inhibit the death of beta cells caused by enhanced levels of inflammatory cytokines. In fact, mouse models of type 1 diabetes have revealed that GLP-1 protects islet cells from destruction and may, in fact, be a useful means of preventing onset of the type 1 diabetes^[2].

GLP-1 y apetito

La investigación en modelos de ratón sugiere que la administración de GLP-1, y su primo similar GLP-1, en el cerebro de ratones puede reducir el impulso de comer e inhibir la ingesta de alimentos.^[3]. Parece que el GLP-1 en realidad puede mejorar la sensación de saciedad, ayudando a las personas a sentirse más llenas y reduciendo el hambre indirectamente. Estudios clínicos recientes han demostrado en ratones que la administración dos veces al día de agonistas del receptor GLP-1 provoca una pérdida de peso gradual y lineal. Durante un largo período, esta pérdida de peso se asocia con una mejora significativa en los factores de riesgo cardiovascular y una reducción en los niveles de hemoglobina A1C, siendo este último un marcador indirecto de la gravedad de la diabetes y la calidad del control del azúcar en sangre logrado mediante el tratamiento.^[4].

Beneficios cardiovasculares potenciales del GLP-1

Ahora se sabe que los receptores GLP-1 se distribuyen por todo el corazón y actúan para mejorar la función cardíaca en ciertos entornos al aumentar la frecuencia cardíaca y reducir la presión diastólica final del ventrículo izquierdo.^[5]. The latter may not seem like much, but increased LV end-diastolic pressure is associated with LV hypertrophy, cardiac remodeling, and eventual heart failure. Recent evidence has even suggested that GLP-1 could play role in decreasing the overall damaged caused by a heart attack. It appears that the peptide improves cardiac muscle glucose uptake, thereby helping struggling ischemic heart muscle cells to get the nutrition they need to continue functioning and avoid programmed cell death. The increase in glucose uptake in these cells appears to independent of insulin^[6]. Large infusions of GLP-1 into dogs have been shown to improve LV performance and reduce systemic vascular resistance. The latter effect can help to reduce blood pressure and ease strain on the heart as a result^[7]. Esto, a su vez, puede ayudar a reducir las consecuencias a largo plazo de la presión arterial alta, como la remodelación del VI, el engrosamiento vascular y la insuficiencia cardíaca. Según el Dr. Holst, la administración de GLP-1 después de una lesión cardíaca ha "aumentado constantemente el rendimiento del miocardio tanto en modelos animales experimentales como en pacientes".Size of damage in heart in control mice (A), mice given standard vasopressin therapy (B), and mice give GLP-1 (C). Source:Diabetes Journal

GLP-1 y el cerebro

Existe cierta evidencia que sugiere que el GLP-1 puede mejorar el aprendizaje y ayudar a proteger las neuronas contra enfermedades neurodegenerativas como la enfermedad de Alzheimer. En un estudio, se demostró que el GLP-1 mejora el aprendizaje asociativo y espacial en ratones e incluso mejora los déficits de aprendizaje en ratones con defectos genéticos específicos. En ratas que sobreexpresan el receptor GLP-1 en ciertas regiones del cerebro, el aprendizaje y la memoria son significativamente mejores que en sus controles normales.^[8]. Additional research in mice has shown that GLP-1 can help to protect against excitotoxic neuron damage, completely protecting rat models of neurodegeneration against glutamate-induced apoptosis. The peptide can even stimulate neurite outgrowth in cultured cells. Researchers are hopeful that additional research on GLP-1 will reveal how it might be used to halt or reverse certain neurodegenerative diseases^[9]. Interestingly, GLP-1 and its analogue exendin-4 have been shown in mouse models to reduce levels of amyloid-beta in the brain as well as the beta-amyloid precursor protein found in neurons. Amyloid beta is the primary component of the plaques observed in Alzheimer’s disease, plaques which, while not necessarily known to be causative, are associated with the severity of the disease. It remains to be seen if preventing amyloid beta accumulation can protect against the effects of Alzheimer’s disease, but this research is, at the very least, a tantalizing clue as to how scientists my intervene in the progression of mild cognitive impairment to full Alzheimer’s disease^[10]. GLP-1 exhibits minimal to moderate side effects, low oral and excellent subcutaneous bioavailability in mice. Per kg dosage in mice does not scale to humans. GLP-1 for sale at

In 1986 ProfessorJens Juul Holstdiscovered the GLP-1 hormone in connection with his work on stomach ulcer surgery. Since the discovery, Novo Nordisk have used theresearchto successfully develop products to treat diabetes and obesity.The hormone GLP-1 can be used to regulate blood sugar levels and satiety. Not only has it made treatment of obesity and diabetes possible, it has also proven useful preventatively through early diagnosis for citizens who are at risk of developing diabetes and obesity. In 2015, Jens Juul Holst received the prestigious international Fernström prize for his research on GLP-1. He is one of the most cited researchers in Europe, with over 1,200 published articles and citations in over 3,500 articles annually. Professor Jens Juul Holst is being referenced as one of the leading scientists involved in the research and development of GLP-1. In no way is this doctor/scientist endorsing or advocating the purchase, sale, or use of this product for any reason. There is no affiliation or relationship, implied or otherwise, between

“The Physiology of Glucagon-like Peptide 1 | Physiological Reviews.” [Online]. “Combined treatment with lisofylline and exendin-4 reverses autoimmune diabetes. - PubMed - NCBI.” [Online]. “The proglucagon-derived peptide, glucagon-like peptide-2, is a neurotransmitter involved in the regulation of food intake. - PubMed - NCBI.” [Online]. “Interim analysis of the effects of exenatide treatment on A1C, weight and cardiovascular risk factors over 82 weeks in 314 overweight patients with... - PubMed - NCBI.” [Online]. “Cardiac function in mice lacking the glucagon-like peptide-1 receptor. - PubMed - NCBI.” [Online]. “Glucagon-like Peptide 1 Can Directly Protect the Heart Against Ischemia/Reperfusion Injury | Diabetes.” [Online]. “Recombinant glucagon-like peptide-1 increases myocardial glucose uptake and improves left ventricular performance in conscious dogs with pacing-ind... - PubMed - NCBI.” [Online]. “Glucagon-like peptide-1 receptor is involved in learning and neuroprotection. - PubMed - NCBI.” [Online]. “Protection and reversal of excitotoxic neuronal damage by glucagon-like peptide-1 and exendin-4. - PubMed - NCBI.” [Online]. “A new Alzheimer’s disease interventive strategy: GLP-1. - PubMed - NCBI.” [Online]. Holst JJ. From the Incretin Concept and the Discovery of GLP-1 to Today's Diabetes Therapy.Front Endocrinol (Lausanne). 2019;10:260. Published 2019 Apr 26. doi:10.3389/fendo.2019.00260https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497767/

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