Irisin and Incretin Hormones: Similarities, Differences, and Implications in Type 2 Diabetes and Obesity

Abstract

Incretins are gut hormones that potentiate glucose-stimulated insulin secretion (GSIS) after meals. Glucagon-like peptide-1 (GLP-1) is the most investigated incretin hormone, synthesized mainly by L cells in the lower gut tract. GLP-1 promotes β-cell function and survival and exerts beneficial effects in different organs and tissues. Irisin, a myokine released in response to a high-fat diet and exercise, enhances GSIS. Similar to GLP-1, irisin augments insulin biosynthesis and promotes accrual of β-cell functional mass. In addition, irisin and GLP-1 share comparable pleiotropic effects and activate similar intracellular pathways. The insulinotropic and extra-pancreatic effects of GLP-1 are reduced in type 2 diabetes (T2D) patients but preserved at pharmacological doses. GLP-1 receptor agonists (GLP-1RAs) are therefore among the most widely used antidiabetes drugs, also considered for their cardiovascular benefits and ability to promote weight loss. Irisin levels are lower in T2D patients, and in diabetic and/or obese animal models irisin administration improves glycemic control and promotes weight loss. Interestingly, recent evidence suggests that both GLP-1 and irisin are also synthesized within the pancreatic islets, in α- and β-cells, respectively. This review aims to describe the similarities between GLP-1 and irisin and to propose a new potential axis–involving the gut, muscle, and endocrine pancreas that controls energy homeostasis.

Irisin—A Pancreatic Islet Hormone

“…Interesting similarities exist between irisin and glucagon-like peptide 1 (GLP-1), the latter of which is used in the treatment of type 2 diabetes as a GLP-1 receptor agonist. They share common features, such as an increased secretion in response to carbohydrates and lipids [ 27 ], and seem to be interconnected in the regulation of glucose metabolism, since both irisin synthesis and GLP-1 secretion are increased by metformin treatment [ 28 , 29 ]. In addition, 12 weeks of treatment with a GLP-1 analog increased the levels of irisin in T2D patients [ 30 ].…”

“…In addition, 12 weeks of treatment with a GLP-1 analog increased the levels of irisin in T2D patients [ 30 ]. Specifically in the pancreas, both have previously been shown to increase β-cell survival, proliferation and insulin secretion [ 27 ]. In addition, similar to what we observed for irisin, GLP-1 has been found to reduce IBF [ 31 ].…”

Pengaruh Irisin pada Pencoklatan Lemak Putih

“…Berdasarkan Boström et al irisin memicu pencoklatan jaringan adiposa putih (WAT) yang di stimulasi dari ekspresi uncoupling protein 1 (UCP1) dimana menurunkan karakteristik regulasi gen sehingga memicu termogenesis dan pengeluaran energi (Boström et al, 2012). Pada adiposit manusia, kemampuan untuk menginduksi pencoklatan jaringan adiposa putih masih diperdebatkan (Marrano et al, 2021). Zhang et menemukan bahwa efek irisin pada manusia tergantung pada tahap diferensiasi karena irisin menginduksi pencoklatan jaringan adiposa putih pada adiposit matang dengan meningkatkan termogenesis seluler dan irisin menghambat adipogenesis (Zhang et al, 2016).…”

L’irisina: un ormone con benefici multiorgano

“…A sostegno di quest'ultimo concetto, alcuni studi hanno riportato l'esistenza di correlazioni positive tra i livelli sierici di irisina e alcuni marker di adiposità e di disturbi dell'omeostasi del glucosio e dei lipidi [7]. Questo suggerisce la possibilità che l'alterazione dei livelli sierici di irisina possa contribuire ad alterare l'omeostasi metabolica ed energetica e promuovere l'insorgenza di patologie metaboliche, tra cui il DMT2.…”