Specialized Proresolving Lipid Mediators: A Potential Therapeutic Target for Atherosclerosis.

Cardiovascular disease (CVD) is a global public health issue due to its high morbidity, mortality, and economic impact. The implementation of innovative therapeutic alternatives for CVD is urgently required. Specialized proresolving lipid mediators (SPMs) are bioactive compounds derived from ω-3 and ω-6 fatty acids, integrated into four families: Lipoxins, Resolvins, Protectins, and Maresins. SPMs have generated interest in recent years due to their ability to promote the resolution of inflammation associated with the pathogeneses of numerous illnesses, particularly CVD. Several preclinical studies in animal models have evidenced their ability to decrease the progression of atherosclerosis, intimal hyperplasia, and reperfusion injury via diverse mechanisms. Large-scale clinical trials are required to determine the effects of SPMs in humans. This review integrates the currently available knowledge of the therapeutic impact of SPMs in CVD from preclinical and clinical studies, along with the implicated molecular pathways. In vitro results have been promising, and as such, SPMs could soon represent a new therapeutic alternative for CVD.

The Role of the α Cell in the Pathogenesis of Diabetes: A World beyond the Mirror.

Type 2 Diabetes Mellitus (T2DM) is one of the most prevalent chronic metabolic disorders, and insulin has been placed at the epicentre of its pathophysiological basis. However, the involvement of impaired alpha (α) cell function has been recognized as playing an essential role in several diseases, since hyperglucagonemia has been evidenced in both Type 1 and T2DM. This phenomenon has been attributed to intra-islet defects, like modifications in pancreatic α cell mass or dysfunction in glucagon's secretion. Emerging evidence has shown that chronic hyperglycaemia provokes changes in the Langerhans' islets cytoarchitecture, including α cell hyperplasia, pancreatic beta (ß) cell dedifferentiation into glucagon-positive producing cells, and loss of paracrine and endocrine regulation due to ß cell mass loss. Other abnormalities like α cell insulin resistance, sensor machinery dysfunction, or paradoxical ATP-sensitive potassium channels (KATP) opening have also been linked to glucagon hypersecretion. Recent clinical trials in phases 1 or 2 have shown new molecules with glucagon-antagonist properties with considerable effectiveness and acceptable safety profiles. Glucagon-like peptide-1 (GLP-1) agonists and Dipeptidyl Peptidase-4 inhibitors (DPP-4 inhibitors) have been shown to decrease glucagon secretion in T2DM, and their possible therapeutic role in T1DM means they are attractive as an insulin-adjuvant therapy.

Is "Leptin Resistance" Another Key Resistance to Manage Type 2 Diabetes?

Although novel pharmacological options for the treatment of type 2 diabetes mellitus (DM2) have been observed to modulate the functionality of several key organs in glucose homeostasis, successful regulation of insulin resistance (IR), body weight management, and pharmacological treatment of obesity remain notable problems in endocrinology. Leptin may be a pivotal player in this scenario, as an adipokine which centrally regulates appetite and energy balance. In obesity, excessive caloric intake promotes a low-grade inflammatory response, which leads to dysregulations in lipid storage and adipokine secretion. In turn, these entail alterations in leptin sensitivity, leptin transport across the blood-brain barrier and defects in post-receptor signaling. Furthermore, hypothalamic inflammation and endoplasmic reticulum stress may increase the expression of molecules which may disrupt leptin signaling. Abundant evidence has linked obesity and leptin resistance, which may precede or occur simultaneously to IR and DM2. Thus, leptin sensitivity may be a potential early therapeutic target that demands further preclinical and clinical research. Modulators of insulin sensitivity have been tested in animal models and small clinical trials with promising results, especially in combination with agents such as amylin and GLP-1 analogs, in particular, due to their central activity in the hypothalamus.

Rol de la estevia y L-carnitina sobre el impacto glicémico de un suplemento nutricional en adultos / Role of the stevia and L-carnitine of a nutritional supplement on glycemic impact in adults

Actualmente la industria alimentaria ha generado interés en edulcorantes no nutritivos, por ejemplo la estevia y en componentes especiales como la L-carnitina, utilizados en formulaciones de suplementos nutricionales para el control glicémico específicos para diabéticos. El presente estudio evaluó el efecto de la estevia y la L-carnitina sobre el índice glicémico (IG) y la carga glicémica (CG) de un suplemento nutricional en 19 sujetos sanos (9 hombres y 10 mujeres), quienes completaron aleatoriamente 3 pruebas de consumo, 1 para el suplemento y 1 para cada producto de referencia: solución glucosada (SG) y pan blanco (PB), obteniendo muestras de sangre a los tiempos 0, 15, 30, 45, 60, 90 y 120 min; para medición de glicemias, e insulina basal y postprandial. El área de incremento bajo la curva de glucosa (IAUC) fue menor para el suplemento 11.778,73 que para los productos de referencia (SG) 13.724,06; (PB) 13.153,56 α = p 0,005. El IG = (62) y la CG = (16) resultaron intermedios y más bajos que el del pan blanco IG = (69) y la CG = (18), sin diferencias en la insulina postprandial. Esto demuestra que este suplemento nutricional formulado con estevia y L-carnitina es capaz de prolongar la respuesta glicémica sin aumentar los requerimientos insulínicos en sujetos sanos. Se requieren estudios específicos en diabéticos para validar si el impacto glicémico es menor que el producto patrón. La presencia de otros nutrientes en la fórmula, influyentes en estos indicadores, no permite inferir que los resultados se deban únicamente al tipo de endulzante utilizado y a la L-carnitina (AU)

Currently the food industry has generated interest in non-nutritive sweeteners, for example Stevia and in special components such as L-carnitine, used in formulations of nutritional supplements for glycemic control specific for diabetics. The present study evaluated the effect of stevia and L-carnitine on the glycemic index (GI) and glycemic load (CG) of a nutritional supplement in 19 healthy subjects (9 men and 10 women), who randomly completed 3 consumption tests, 1 for the supplement and 1 for each reference product: Glucose solution (SG) and white bread (PB), obtaining blood samples at the 0, 15, 30, 45, 60, 90 and 120 min times; for measurement of blood glucose, basal and postprandial insulin. The increase area under the glucose curve (IAUC) was lower for supplement 11,778.73 than for reference products (SG) 13,724.06; (PB) 13,153.56 α = p 0.005. IG = (62) and CG = (16) were intermediate and lower than white bread IG = (69) and CG = (18), with no difference in postprandial insulin. This demonstrates that this nutritional supplement formulated with stevia and L-carnitine is able to prolong the glycemic response without increasing the insulin requirements in healthy subjects. Specific studies are required in diabetics to validate whether the glycemic impact is lower than the standard product. The presence of other nutrients in the formula, influential in these indicators, does not allow to infer that the results are due only to the type of sweetener used and the L-carnitine (AU)