1018-P: Comparison of Short- and Long-Acting Glucagon-Like Peptide-1 Receptor Agonist Effects on Postprandial Glucose and Lipid Excursion via Gastric Emptying

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1018-P
Author(s):  
HITOSHI KUWATA ◽  
DAISUKE YABE ◽  
YOSHIYUKI HAMAMOTO ◽  
TAKESHI KUROSE ◽  
YUTAKA SEINO
Keyword(s):  
Gastric Emptying ◽  
Receptor Agonist ◽  
Postprandial Glucose ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Long Acting

scholarly journals Oleoylethanolamide modulates glucagon-like peptide-1 receptor agonist signaling and enhances exendin-4-mediated weight loss in obese mice

2018 ◽  
Vol 315 (4) ◽  
pp. R595-R608 ◽  
Author(s):  
Jacob D. Brown ◽  
Danielle McAnally ◽  
Jennifer E. Ayala ◽  
Melissa A. Burmeister ◽  
Camilo Morfa ◽  
...  
Keyword(s):  
Weight Loss ◽  
Energy Expenditure ◽  
Receptor Agonist ◽  
Day Treatment ◽  
Mtor Pathway ◽  
Obese Mice ◽  
Promote Weight Loss ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Long Acting

Long-acting glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonists (GLP-1RA), such as exendin-4 (Ex4), promote weight loss. On the basis of a newly discovered interaction between GLP-1 and oleoylethanolamide (OEA), we tested whether OEA enhances GLP-1RA-mediated anorectic signaling and weight loss. We analyzed the effect of GLP-1+OEA and Ex4+OEA on canonical GLP-1R signaling and other proteins/pathways that contribute to the hypophagic action of GLP-1RA (AMPK, Akt, mTOR, and glycolysis). We demonstrate that OEA enhances canonical GLP-1R signaling when combined with GLP-1 but not with Ex4. GLP-1 and Ex4 promote phosphorylation of mTOR pathway components, but OEA does not enhance this effect. OEA synergistically enhanced GLP-1- and Ex4-stimulated glycolysis but did not augment the hypophagic action of GLP-1 or Ex4 in lean or diet-induced obese (DIO) mice. However, the combination of Ex4+OEA promoted greater weight loss in DIO mice than Ex4 or OEA alone during a 7-day treatment. This was due in part to transient hypophagia and increased energy expenditure, phenotypes also observed in Ex4-treated DIO mice. Thus, OEA augments specific GLP-1RA-stimulated signaling but appears to work in parallel with Ex4 to promote weight loss in DIO mice. Elucidating cooperative mechanisms underlying Ex4+OEA-mediated weight loss could, therefore, be leveraged toward more effective obesity therapies.

scholarly journals Therapeutic Effect of Exendin-4, a Long-Acting Analogue of Glucagon-Like Peptide-1 Receptor Agonist, on Nerve Regeneration after the Crush Nerve Injury

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Koji Yamamoto ◽  
Masatoshi Amako ◽  
Yoritsuna Yamamoto ◽  
Toyokazu Tsuchihara ◽  
Hitoshi Nukada ◽  
...  
Keyword(s):  
Nerve Regeneration ◽  
Nerve Injury ◽  
Receptor Agonist ◽  
Tibialis Anterior Muscle ◽  
Sciatic Nerve Crush ◽  
Nerve Crush ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Long Acting

Glucagon-like peptide-1 (GLP-1) is glucose-dependent insulinotropic hormone secreted from enteroendocrine L cells. Its long-acting analogue, exendin-4, is equipotent to GLP-1 and is used to treat type 2 diabetes mellitus. In addition, exendin-4 has effects on the central and peripheral nervous system. In this study, we administered repeated intraperitoneal (i.p.) injections of exendin-4 to examine whether exendin-4 is able to facilitate the recovery after the crush nerve injury. Exendin-4 injection was started immediately after crush injury and was repeated every day for subsequent 14 days. Rats subjected to sciatic nerve crush exhibited marked functional loss, electrophysiological dysfunction, and atrophy of the tibialis anterior muscle (TA). All these changes, except for the atrophy of TA, were improved significantly by the administration of exendin-4. Functional, electrophysiological, and morphological parameters indicated significant enhancement of nerve regeneration 4 weeks after nerve crush. These results suggest that exendin-4 is feasible for clinical application to treat peripheral nerve injury.

scholarly journals Influence of gastric emptying on the control of postprandial glycemia: physiology and therapeutic implications

2014 ◽  
Vol 12 (2) ◽  
pp. 251-253 ◽  
Author(s):  
Marcos Antonio Tambascia ◽  
Domingos Augusto Cherino Malerbi ◽  
Freddy Goldberg Eliaschewitz
Keyword(s):  
Gastric Emptying ◽  
Glucose Homeostasis ◽  
Neural Mechanism ◽  
Postprandial Glucose ◽  
Therapeutic Implications ◽  
Intrinsic Factors ◽  
Postprandial Glycemia ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Extrinsic And Intrinsic Factors

The maintenance of glucose homeostasis is complex and involves, besides the secretion and action of insulin and glucagon, a hormonal and neural mechanism, regulating the rate of gastric emptying. This mechanism depends on extrinsic and intrinsic factors. Glucagon-like peptide-1 secretion regulates the speed of gastric emptying, contributing to the control of postprandial glycemia. The pharmacodynamic characteristics of various agents of this class can explain the effects more relevant in fasting or postprandial glucose, and can thus guide the individualized treatment, according to the clinical and pathophysiological features of each patient.

Efpeglenatide, a Long-Acting Glucagon-Like Peptide-1 Receptor Agonist—Immunogenicity Profile Based on Preclinical and Clinical Studies

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1097-P ◽  
Author(s):  
STEFANO DEL PRATO ◽  
IN YOUNG CHOI ◽  
JAHOON KANG ◽  
MICHAEL E. TRAUTMANN ◽  
KUN-HO YOON ◽  
...  
Keyword(s):  
Clinical Studies ◽  
Receptor Agonist ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Long Acting ◽  
Preclinical And Clinical Studies
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