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1.
PLoS One ; 19(4): e0301496, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38635745

RESUMEN

Obesity leads to insulin resistance (IR) and type 2 diabetes. In humans, low levels of the hormone prolactin (PRL) correlate with IR, adipose tissue (AT) dysfunction, and increased prevalence of T2D. In obese rats, PRL treatment promotes insulin sensitivity and reduces visceral AT adipocyte hypertrophy. Here, we tested whether elevating PRL levels with the prokinetic and antipsychotic drug sulpiride, an antagonist of dopamine D2 receptors, improves metabolism in high fat diet (HFD)-induced obese male mice. Sulpiride treatment (30 days) reduced hyperglycemia, IR, and the serum and pancreatic levels of triglycerides in obese mice, reduced visceral and subcutaneous AT adipocyte hypertrophy, normalized markers of visceral AT function (PRL receptor, Glut4, insulin receptor and Hif-1α), and increased glycogen stores in skeletal muscle. However, the effects of sulpiride reducing hyperglycemia were also observed in obese prolactin receptor null mice. We conclude that sulpiride reduces obesity-induced hyperglycemia by mechanisms that are independent of prolactin/prolactin receptor activity. These findings support the therapeutic potential of sulpiride against metabolic dysfunction in obesity.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hiperglucemia , Resistencia a la Insulina , Humanos , Ratones , Masculino , Ratas , Animales , Ratones Obesos , Antagonistas de los Receptores de Dopamina D2 , Prolactina , Receptores de Prolactina , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Sulpirida/farmacología , Sulpirida/uso terapéutico , Obesidad/tratamiento farmacológico , Obesidad/etiología , Dieta Alta en Grasa/efectos adversos , Hiperglucemia/tratamiento farmacológico , Hipertrofia , Insulina/metabolismo
2.
Front Endocrinol (Lausanne) ; 13: 1001703, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36213259

RESUMEN

The role of prolactin (PRL) favoring metabolic homeostasis is supported by multiple preclinical and clinical studies. PRL levels are key to explaining the direction of its actions. In contrast with the negative outcomes associated with very high (>100 µg/L) and very low (<7 µg/L) PRL levels, moderately high PRL levels, both within but also above the classically considered physiological range are beneficial for metabolism and have been defined as HomeoFIT-PRL. In animal models, HomeoFIT-PRL levels counteract insulin resistance, glucose intolerance, adipose tissue hypertrophy and fatty liver; and in humans associate with reduced prevalence of insulin resistance, fatty liver, glucose intolerance, metabolic syndrome, reduced adipocyte hypertrophy, and protection from type 2 diabetes development. The beneficial actions of PRL can be explained by its positive effects on main metabolic organs including the pancreas, liver, adipose tissue, and hypothalamus. Here, we briefly review work supporting PRL as a promoter of metabolic homeostasis in rodents and humans, the PRL levels associated with metabolic protection, and the proposed mechanisms involved. Finally, we discuss the possibility of using drugs elevating PRL for the treatment of metabolic diseases.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hígado Graso , Intolerancia a la Glucosa , Resistencia a la Insulina , Animales , Humanos , Hipertrofia , Prolactina/metabolismo
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