Effects of the POMC System on Glucose Homeostasis and Potential Therapeutic Targets for Obesity and Diabetes

Abstract

The hypothalamus is indispensable in energy regulation and glucose homeostasis. Previous studies have shown that pro-opiomelanocortin neurons receive both central neuronal signals, such as α-melanocyte-stimulating hormone, β-endorphin, and adrenocorticotropic hormone, as well as sense peripheral signals such as leptin, insulin, adiponectin, glucagon-like peptide-1, and glucagon-like peptide-2, affecting glucose metabolism through their corresponding receptors and related signaling pathways. Abnormalities in these processes can lead to obesity, type 2 diabetes, and other metabolic diseases. However, the mechanisms by which these signal molecules fulfill their role remain unclear. Consequently, in this review, we explored the mechanisms of these hormones and signals on obesity and diabetes to suggest potential therapeutic targets for obesity-related metabolic diseases. Multi-drug combination therapy for obesity and diabetes is becoming a trend and requires further research to help patients to better control their blood glucose and improve their prognosis.

Obesity and the nervous system

“…Нейроны ПОМК получают как центральные сигналы, такие как α-МСГ, β-эндорфин и АКТГ, так и периферические сигналы: лептин, инсулин, адипонектин, глюкагоноподобный пептид-1 и глюкагоноподобный пептид-2, влияющие на метаболизм глюкозы через соответствующие рецепторы и родственные сигнальные пути. Нарушения в этих процессах могут привести к ожирению [8].…”

“…Гипоталамическое нейровоспаление, промотирующее глиоз и нейрональную смерть [19], может быть основано в т.ч. на эффектах лептина и инсулина, а также факторов, которые могут действовать через систему ПОМК: SMAD7 (Suppressor of Mothers Against Decapentaplegic 7), факторы, индуцируемые гипоксией (Hypoxia-Inducible Factors, HIF), сиртуин 6 и коактиватор стероидных рецепторов-2 [8].…”