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

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 286
Author(s):  
Nicola Marrano ◽  
Giuseppina Biondi ◽  
Anna Borrelli ◽  
Angelo Cignarelli ◽  
Sebastio Perrini ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Weight Loss ◽  
Energy Homeostasis ◽  
Cell Function ◽  
Gut Hormones ◽  
Insulin Biosynthesis ◽  
Β Cell ◽  
Beneficial Effects ◽  
Β Cell Function

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.

scholarly journals Liraglutide in Combination with Metformin or Sulfonylurea for the Treatment of Type 2 Diabetes in Adult patients

2012 ◽  
Vol 4 ◽  
pp. CMT.S7283
Author(s):  
Maneesh V Udiawar ◽  
Stephen C Bain
Keyword(s):  
Type 2 Diabetes ◽  
Clinical Trials ◽  
Cell Function ◽  
Β Cell ◽  
Beneficial Effects ◽  
Number Of Patients ◽  
Β Cell Function ◽  
Glucagon Like Peptide 1 ◽  
Glycemic Targets

Type 2 diabetes is a progressive disease characterized by decline in β-cell function and insulin resistance. The development of liraglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, has been shown in clinical trials to be an effective drug with beneficial effects on β-cell function and improved glycemic control, without the side effects of weight gain and hypoglycemia that frequently limit the use of oral anti-diabetic drugs. Furthermore, its prolonged half-life makes it suitable for once daily administration. Liraglutide is demonstrated to be an effective agent in combination with commonly used oral antidiabetic drugs such as metformin and sulphonylureas, with a significant number of patients achieving their glycemic targets without hypoglycemia. In this review, the results from clinical trials utilizing liraglutide in combination with metformin or sulphonylurea are summarized with regards to efficacy and safety.

scholarly journals Effects of Liraglutide on Weight Loss, Fat Distribution, and β-Cell Function in Obese Subjects With Prediabetes or Early Type 2 Diabetes

Diabetes Care ◽  
2017 ◽  
Vol 40 (11) ◽  
pp. 1556-1564 ◽  
Author(s):  
Francesca Santilli ◽  
Paola G. Simeone ◽  
Maria T. Guagnano ◽  
Marika Leo ◽  
Marica T. Maccarone ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Weight Loss ◽  
Cell Function ◽  
Fat Distribution ◽  
Early Type ◽  
Β Cell ◽  
Β Cell Function ◽  
Obese Subjects

scholarly journals Serum Amylase Levels in Relation to Islet β Cell Function in Patients with Early Type 2 Diabetes

PLoS ONE ◽  
2016 ◽  
Vol 11 (9) ◽  
pp. e0162204 ◽  
Author(s):  
Lei Zhuang ◽  
Jian-bin Su ◽  
Xiu-lin Zhang ◽  
Hai-yan Huang ◽  
Li-hua Zhao ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Serum Amylase ◽  
Cell Function ◽  
Early Type ◽  
Β Cell ◽  
Β Cell Function

Let7b-5p is Upregulated in the Serum of Emirati Patients with Type 2 Diabetes and Regulates Insulin Secretion in INS-1 Cells

2020 ◽  
Author(s):  
Hayat Aljaibeji ◽  
Noha Mousaad Elemam ◽  
Abdul Khader Mohammed ◽  
Hind Hasswan ◽  
Mahammad Al Thahyabat ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Cell Viability ◽  
Cell Function ◽  
Serum Levels ◽  
Insulin Content ◽  
Β Cell ◽  
Control Subjects ◽  
Β Cell Function

Abstract Let7b-5p is a member of the Let-7 miRNA family and one of the top expressed miRNAs in human islets that implicated in glucose homeostasis. The levels of Let7b-5p in type 2 diabetes (T2DM) patients or its role in β-cell function is still unclear. In the current study, we measured the serum levels of let7b-5p in Emirati patients with T2DM (with/without complications) and control subjects. Overexpression or silencing of let7b-5p in INS-1 (832/13) cells was performed to investigate the impact on insulin secretion, content, cell viability, apoptosis, and key functional genes. We found that serum levels of let7b-5p are significantly (p<0.05) higher in T2DM-patients or T2DM with complications compared to control subjects. Overexpression of let7b-5p increased insulin content and decreased glucose-stimulated insulin secretion, whereas silencing of let7b-5p reduced insulin content and secretion. Modulation of the expression levels of let7b-5p did not influence cell viability nor apoptosis. Analysis of mRNA and protein expression of hallmark genes in let7b-5p transfected cells revealed a marked dysregulation of Insulin, Pancreatic And Duodenal Homeobox 1 (PDX1), glucokinase (GCK), glucose transporter 2 (GLUT2), and INSR. In conclusion, an appropriate level of let7b-5p is essential to maintain β-cell function and may be regarded as a biomarker for T2DM.

scholarly journals Imeglimin Amplifies Glucose-Stimulated Insulin Release from Diabetic Islets via a Distinct Mechanism of Action

2020 ◽  
Author(s):  
Sophie Hallakou-Bozec ◽  
Micheline Kergoat ◽  
Pascale Fouqueray ◽  
Sébastien Bolze ◽  
David E. Moller
Keyword(s):  
Type 2 Diabetes ◽  
Mode Of Action ◽  
Cell Function ◽  
Drug Candidate ◽  
Β Cell ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Predominant Component ◽  
Cyclic Adp Ribose ◽  
Β Cell Function

ABSTRACTPancreatic islet β-cell dysfunction is characterized by defective glucose-stimulated insulin secretion (GSIS) and is a predominant component of the pathophysiology of diabetes. Imeglimin, a novel first-in-class small molecule tetrahydrotriazine drug candidate, improves glycemia and GSIS in preclinical models and clinical trials in patients with type 2 diabetes; however, the mechanism by which it restores β-cell function is unknown. Here, we show that Imeglimin acutely and directly amplifies GSIS in islets isolated from rodents with Type 2 diabetes via a mode of action that is distinct from other known therapeutic approaches. The underlying mechanism involves increases in the cellular nicotinamide adenine dinucleotide (NAD+) pool – potentially via the salvage pathway and induction of nicotinamide phosphoribosyltransferase (NAMPT) along with augmentation of glucose-induced ATP levels. Further, additional results suggest that NAD+ conversion to a second messenger, cyclic ADP ribose (cADPR), via cyclic ADP ribose hydrolase (CD38) is required for Imeglimin’s effects in islets, thus representing a potential link between increased NAD+ and enhanced glucose-induced Ca2+ mobilization which - in turn - is known to drive insulin granule exocytosis. Collectively, these findings implicate a novel mode of action for Imeglimin that explains its ability to effectively restore β-cell function and provides for a new approach to treat patients suffering from Type 2 diabetes.

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