Research Article Details

Article ID: A03677
PMID: 33907839
Source: Int J Mol Med
Title: Role of 2‑series prostaglandins in the pathogenesis of type 2 diabetes mellitus and non‑alcoholic fatty liver disease (Review).
Abstract: Nowadays, metabolic syndromes are emerging as global epidemics, whose incidence are increasing annually. However, the efficacy of therapy does not increase proportionately with the increased morbidity. Type 2 diabetes mellitus (T2DM) and non‑alcoholic fatty liver disease (NAFLD) are two common metabolic syndromes that are closely associated. The pathogenic mechanisms of T2DM and NAFLD have been studied, and it was revealed that insulin resistance, hyperglycemia, hepatic lipid accumulation and inflammation markedly contribute to the development of these two diseases. The 2‑series prostaglandins (PGs), a subgroup of eicosanoids, including PGD2, PGE2, PGF2α and PGI2, are converted from arachidonic acid catalyzed by the rate‑limiting enzymes cyclooxygenases (COXs). Considering their wide distribution in almost every tissue, 2‑series PG pathways exert complex and interlinked effects in mediating pancreatic β‑cell function and proliferation, insulin sensitivity, fat accumulation and lipolysis, as well as inflammatory processes. Previous studies have revealed that metabolic disturbances, such as hyperglycemia and hyperlipidemia, can be improved by treatment with COX inhibitors. At present, an accumulating number of studies have focused on the roles of 2‑series PGs and their metabolites in the pathogenesis of metabolic syndromes, particularly T2DM and NAFLD. In the present review, the role of 2‑series PGs in the highly intertwined pathogenic mechanisms of T2DM and NAFLD was discussed, and important therapeutic strategies based on targeting 2‑series PG pathways in T2DM and NAFLD treatment were provided.
DOI: 10.3892/ijmm.2021.4947

Strategy ID Therapy Strategy Synonyms Therapy Targets Therapy Drugs
S01 Improve insulin resistance insulin sensitizer; insulin resistance; glucose tolerance Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide Details
S02 Enhance lipid metabolism triglyceride-lowering; lipid tolerance; lipid metabolism 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; Details
S05 Anti-inflammatory inflammatory Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; Details

Target ID Target Name GENE Action Class UniProtKB ID Entry Name
T18 Acetyl-CoA carboxylase 1 ACACA inhibitor Enzyme Q13085 ACACA_HUMAN Details

Diseases ID DO ID Disease Name Definition Class
I05 9352 Type 2 diabetes mellitus A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus Details

Drug ID Drug Name Type DrugBank ID Targets Category Latest Progress
D328 Serine Chemical drug DB00133 SRR Improve insulin resistance Under clinical trials Details
D579 Emfilermin Miscellany -- adipocytes Enhance lipid metabolism Under investigation Details
D182 Insulin Biological drug DB00030 INSR agonist; CPE modulator&product of -- Under clinical trials Details