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.
Highlights
Incretins are gut hormones that potentiate insulin secretion after meal ingestion in a glucose-dependent manner
The two best-studied incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), exert insulinotropic actions through distinct G-protein-coupled receptors (GIP-R and GLP-1R respectively) that are highly expressed on islet β-cells and on α- and δ-cells, as well as in nonislet cells [2,3]
It has been amply demonstrated that the “incretin effect” is typically reduced or even absent in people with impaired glucose tolerance or diabetes, and this contributes to defective insulin secretion and hyperglycaemia in patients with type 2 diabetes (T2D) [1]
Summary
Incretins are gut hormones that potentiate insulin secretion after meal ingestion in a glucose-dependent manner. Many studi have explored the pleiotropic properties of irisin, demonstrating its pivotal role in th properties of irisin, demonstrating its pivotal role in the regulation of energy metabolism, by regulation of energy metabolism, by acting on several tissues and intervening in nu acting on several tissues and intervening in numerous biochemical pathways. GLP-1 and irisin andand to propose new potential axis—involving the gut, muscle, and GLP-1 irisin anda to propose a new potential axis—involving the gut, muscle, an endocrine pancreas—relevant for the controlforofthe energy homeostasis.
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