Recent advances in understanding GLP-1R (glucagon-like peptide-1 receptor) function

2013 ◽  
Vol 41 (1) ◽  
pp. 172-179 ◽  
Author(s):  
Cassandra Koole ◽  
Kavita Pabreja ◽  
Emilia E. Savage ◽  
Denise Wootten ◽  
Sebastian G.B. Furness ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cell Mass ◽  
Insulin Biosynthesis ◽  
Ongoing Research ◽  
Beneficial Effects ◽  
Future Drug ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
New Treatments

Type 2 diabetes is a major global health problem and there is ongoing research for new treatments to manage the disease. The GLP-1R (glucagon-like peptide-1 receptor) controls the physiological response to the incretin peptide, GLP-1, and is currently a major target for the development of therapeutics owing to the broad range of potential beneficial effects in Type 2 diabetes. These include promotion of glucose-dependent insulin secretion, increased insulin biosynthesis, preservation of β-cell mass, improved peripheral insulin sensitivity and promotion of weight loss. Despite this, our understanding of GLP-1R function is still limited, with the desired spectrum of GLP-1R-mediated signalling yet to be determined. We review the current understanding of GLP-1R function, in particular, highlighting recent contributions in the field on allosteric modulation, probe-dependence and ligand-directed signal bias and how these behaviours may influence future drug development.

The complexity of signalling mediated by the glucagon-like peptide-1 receptor

2016 ◽  
Vol 44 (2) ◽  
pp. 582-588 ◽  
Author(s):  
Madeleine M. Fletcher ◽  
Michelle L. Halls ◽  
Arthur Christopoulos ◽  
Patrick M. Sexton ◽  
Denise Wootten
Keyword(s):  
Type 2 Diabetes ◽  
Cell Mass ◽  
Peripheral Tissues ◽  
Biased Agonism ◽  
Temporal Aspects ◽  
Class B ◽  
Future Drug ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

The glucagon-like peptide-1 receptor (GLP-1R) is a class B GPCR that is a major therapeutic target for the treatment of type 2 diabetes. The receptor is activated by the incretin peptide GLP-1 promoting a broad range of physiological effects including glucose-dependent insulin secretion and biosynthesis, improved insulin sensitivity of peripheral tissues, preservation of β-cell mass and weight loss, all of which are beneficial in the treatment of type 2 diabetes. Despite this, existing knowledge surrounding the underlying signalling mechanisms responsible for the physiological actions downstream of GLP-1R activation is limited. Here, we review the current understanding around GLP-1R-mediated signalling, in particular highlighting recent contributions to the field on biased agonism, the spatial and temporal aspects for the control of signalling and how these concepts may influence future drug development.

Pharmacotherapy for Type 2 Diabetes Mellitus: What’s Up and Coming in the Glucagon-Like Peptide-1 (GLP-1) Pipeline?

2021 ◽  
pp. 089719002110490
Author(s):  
Mary J. Elder ◽  
Emily J. Ashjian
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glycemic Control ◽  
Glucagon Secretion ◽  
New Drugs ◽  
Beneficial Effects ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 (GLP-1), an incretin hormone, is known to lower glucose levels, suppress glucagon secretion, and slow gastric emptying. These properties make GLP-1 an ideal target in treating type 2 diabetes mellitus (T2DM). There are many FDA-approved GLP-1 agonists on the market today, several of which have demonstrated benefit beyond improving glycemic control. Given the beneficial effects of GLP-1 agonists in patients with T2DM, new drugs are in development that combine the mechanism of action of GLP-1 receptor agonism with novel mechanisms and with drugs that promote GLP-1 secretion. These agents are designed to improve glycemic control and target greater body weight reduction. This article discusses new GLP-1 drugs in the pipeline for the treatment of T2DM.

Efficacy of dapagliflozin in combination therapy with the glucagon-like peptide-1 analog in obese patients with type 2 diabetes

2015 ◽  
Vol 2 (e1) ◽  
pp. 008-008
Author(s):  
Momoko Isono ◽  
Kazuya Fujihara ◽  
Shoko Furukawa ◽  
Ryo Kumagai ◽  
Hiroaki Yagyu
Keyword(s):  
Type 2 Diabetes ◽  
Combination Therapy ◽  
Obese Patients ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Patient-Reported Outcomes following Initiation of Glucagon-Like Peptide-1 Receptor AgonistS (GLP–1RA) in PatientS with Type 2 Diabetes—PROGRESS-DIABETES Study

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1096-P
Author(s):  
RUTH E. BROWN ◽  
ALEXANDER ABITBOL ◽  
HARPREET S. BAJAJ ◽  
HASNAIN KHANDWALA ◽  
RONALD GOLDENBERG ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Patient Reported Outcomes ◽  
Receptor Agonists ◽  
Patient Reported ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-Like Peptide-1 Is a Significant Determinant of the Second-Meal Effect in Patients with Type 2 Diabetes

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1963-P
Author(s):  
SIGRID BERGMANN ◽  
NATASHA C. BERGMANN ◽  
LÆRKE S. GASBJERG ◽  
JENS J. HOLST ◽  
TINA VILSBØLL ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Significant Determinant ◽  
Meal Effect ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

1019-P: Glucagon-Like Peptide-1 Receptor Agonists Predominantly Reduce Body Fat Mass in Patients with Type 2 Diabetes

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1019-P
Author(s):  
YUKI FUJITA ◽  
SODAI KUBOTA ◽  
HITOSHI KUWATA ◽  
DAISUKE YABE ◽  
YOSHIYUKI HAMAMOTO ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Fat ◽  
Fat Mass ◽  
Body Fat Mass ◽  
Receptor Agonists ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1
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