scholarly journals Detour Ahead: Incretin Hormone Signaling Alters Its Intracellular Path as β-Cell Failure Progresses During Diabetes

2021 ◽  
Vol 12 ◽  
Author(s):  
Mehboob A. Hussain ◽  
Erinn Laimon-Thomson ◽  
Syed M. Mustafa ◽  
Alexander Deck ◽  
Banya Song
2011 ◽  
Vol 25 (12) ◽  
pp. 2134-2143 ◽  
Author(s):  
Shuen-Ing Tschen ◽  
Senta Georgia ◽  
Sangeeta Dhawan ◽  
Anil Bhushan

Endocrinology ◽  
2010 ◽  
Vol 151 (5) ◽  
pp. 1984-1989 ◽  
Author(s):  
Patricia L. Brubaker

The incretin hormone, glucagon-like peptide-1 (GLP-1), is now being used in the clinic to enhance insulin secretion and reduce body weight in patients with type 2 diabetes. Although much is already known about the biology of GLP-1, much remains to be understood. Hence, this review will consider recent findings related to the potential for enhancing endogenous levels of GLP-1 through selective use of secretagogues and the beneficial cardiovascular, neuroprotective, and immunomodulatory effects of GLP-1, as well as the possible effects of GLP-1 to enhance β-cell growth and/or to induce pancreatitis or thyroid cancer. Finally, the potential for molecular medicine to enhance the success of GLP-1 therapy in the clinic is considered. A better understanding of the fundamental biology of GLP-1 may lead to new therapeutic modalities for the clinical use of this intestinal hormone.


2019 ◽  
Vol 104 (11) ◽  
pp. 5703-5714 ◽  
Author(s):  
Ole L Dollerup ◽  
Samuel A J Trammell ◽  
Bolette Hartmann ◽  
Jens J Holst ◽  
Britt Christensen ◽  
...  

Abstract Objective Augmenting nicotinamide adenine dinucleotide (NAD+) metabolism through dietary provision of NAD+ precursor vitamins translates to improved glucose handling in rodent models of obesity and diabetes. Preclinical evidence suggests that the NAD+/SIRT1 axis may be implicated in modulating important gut-related aspects of glucose regulation. We sought to test whether NAD+ precursor supplementation with nicotinamide riboside (NR) affects β-cell function, α-cell function, and incretin hormone secretion as well as circulating bile acid levels in humans. Design A 12-week randomized, double-blind, placebo-controlled, parallel-group trial in 40 males with obesity and insulin resistance allocated to NR at 1000 mg twice daily (n = 20) or placebo (n = 20). Two-hour 75-g oral glucose tolerance tests were performed before and after the intervention, and plasma concentrations of glucose, insulin, C-peptide, glucagon, glucagon-like peptide 1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) were determined. β-Cell function indices were calculated based on glucose, insulin, and C-peptide measurements. Fasting plasma concentrations of bile acids were determined. Results NR supplementation during 12 weeks did not affect fasting or postglucose challenge concentrations of glucose, insulin, C-peptide, glucagon, GLP-1, or GIP, and β-cell function did not respond to the intervention. Additionally, no changes in circulating adipsin or bile acids were observed following NR supplementation. Conclusion The current study does not provide evidence to support that dietary supplementation with the NAD+ precursor NR serves to impact glucose tolerance, β-cell secretory capacity, α-cell function, and incretin hormone secretion in nondiabetic males with obesity. Moreover, bile acid levels in plasma did not change in response to NR supplementation.


2019 ◽  
Vol 133 (22) ◽  
pp. 2317-2327 ◽  
Author(s):  
Nicolás Gómez-Banoy ◽  
James C. Lo

Abstract The growing prevalence of obesity and its related metabolic diseases, mainly Type 2 diabetes (T2D), has increased the interest in adipose tissue (AT) and its role as a principal metabolic orchestrator. Two decades of research have now shown that ATs act as an endocrine organ, secreting soluble factors termed adipocytokines or adipokines. These adipokines play crucial roles in whole-body metabolism with different mechanisms of action largely dependent on the tissue or cell type they are acting on. The pancreatic β cell, a key regulator of glucose metabolism due to its ability to produce and secrete insulin, has been identified as a target for several adipokines. This review will focus on how adipokines affect pancreatic β cell function and their impact on pancreatic β cell survival in disease contexts such as diabetes. Initially, the “classic” adipokines will be discussed, followed by novel secreted adipocyte-specific factors that show therapeutic promise in regulating the adipose–pancreatic β cell axis.


2008 ◽  
Vol 116 (09) ◽  
Author(s):  
SM Schmid ◽  
M Hallschmid ◽  
K Jauch-Chara ◽  
KM Oltmanns ◽  
A Peters ◽  
...  
Keyword(s):  
Β Cell ◽  

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