Research Article Details
| Article ID: | A15723 |
| PMID: | 30603331 |
| Source: | Diabetol Int |
| Title: | Immune regulation of glucose and lipid metabolism. |
| Abstract: | The immune response and metabolic regulation are highly integrated, and their interface maintains a homeostatic system. Their dysfunction can cause obesity and its comorbidities, including insulin resistance, type 2 diabetes, and nonalcoholic fatty liver disease (NAFLD). Endoplasmic reticulum (ER) stress is a central abnormality linking obesity, insulin resistance, and NAFLD. ER stress in response to increased hepatic lipids may decrease the ability of the liver to secrete triglyceride by limiting apolipoprotein B secretion, thereby worsening fatty liver. Overnutrition or obesity activates the innate immune system, with the subsequent recruitment of immune cells that contributes to the development of insulin resistance. A significant advance in our understanding of obesity-induced inflammation and insulin resistance has been a recognition of the critical role of adipose tissue macrophages. A role for chemokines, small proteins that direct the trafficking of immune cells to sites of inflammation, has also been demonstrated. Chemokines activate the production of inflammatory cytokines through specific chemokine receptors. This review highlights the chemokine systems linking obesity to inflammation and insulin resistance. Treatment options that target immune cells with the aim of halting the development of insulin resistance and type 2 diabetes remain limited. DPP-4 inhibitors or micronutrients may contribute to the immune regulation of glucose and lipid metabolism by regulating macrophage polarization, thereby reducing insulin resistance and preventing the progression of NAFLD. A detailed understanding of the immune regulation of glucose and lipid homeostasis can lead to the development of a novel therapy for insulin resistance, type 2 diabetes, and NAFLD. |
| DOI: | 10.1007/s13340-017-0331-1 |
| 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 |
|---|
| 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 |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |