scholarly journals Effects of E2HSA, a Long-Acting Glucagon Like Peptide-1 Receptor Agonist, on Glycemic Control and Beta Cell Function in Spontaneous Diabetic db/db Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Shaocong Hou ◽  
Caina Li ◽  
Yi Huan ◽  
Shuainan Liu ◽  
Quan Liu ◽  
...  
Keyword(s):  
Receptor Agonist ◽  
Cell Function ◽  
Similar Efficacy ◽  
Glucose Lowering ◽  
Glucose Levels ◽  
Weekly Treatment ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Long Acting ◽  
Upregulated Genes

Glucagon like peptide-1 (GLP-1) receptor agonists such as exendin-4 have been widely used but their short half-life limits their therapeutic value. The recombinant protein, E2HSA, is a novel, long-acting GLP-1 receptor agonist generated by the fusion of exendin-4 with human serum albumin. In mouse pancreatic NIT-1 cells, E2HSA activated GLP-1 receptor with similar efficacy as exendin-4. After single-dose administration in ICR mice, E2HSA showed prolonged glucose lowering effects which lasted up to four days and extended inhibition on gastric emptying for at least 72 hours. Chronic E2HSA treatment in db/db mice significantly improved glucose tolerance, reduced elevated nonfasting and fasting plasma glucose levels, and also decreased HbA1c levels. E2HSA also increased insulin secretion and decreased body weight and appetite. Furthermore, immunofluorescence analysis showed that E2HSA increasedβ-cell area, improved islet morphology, and reducedβ-cell apoptosis. In accordance with the promotion ofβ-cell function and survival, E2HSA upregulated genes such as Irs2, Pdx-1, Nkx6.1, and MafA and downregulated the expression levels of FoxO1 and proapoptotic Bcl-2 family proteins. In conclusion, with prolonged glucose lowering effects and promotingβ-cell function and survival, the fusion protein, E2HSA, is a promising new therapeutic for once weekly treatment of type 2 diabetes.

2106-P: Glucagon-Like Peptide-1 Receptor Agonist Exenatide Promotes ß-Cell Function via Activation of PPARd/UCP-2 Pathway

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 2106-P
Author(s):  
YANNA SU ◽  
WEN XU ◽  
BEISI LIN ◽  
ZIYU LIU ◽  
YALAN CHEN ◽  
...  
Keyword(s):  
Receptor Agonist ◽  
Cell Function ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

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 The dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist tirzepatide: a novel cardiometabolic therapeutic prospect

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Enrique Z. Fisman ◽  
Alexander Tenenbaum
Keyword(s):  
Receptor Agonist ◽  
Therapeutic Option ◽  
Insulin Response ◽  
Glucagon Secretion ◽  
Long Term Effects ◽  
Glucose Levels ◽  
Lower Glucose ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Gip Receptor

AbstractIncretin hormones are peptides released in the intestine in response to the presence of nutrients in its lumen. The main incretins are glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). GLP-1 stimulates insulin secretion, inhibits glucagon secretion at pancreatic α cells and has also extrapancreatic influences as slowing of gastric emptying which increases the feeling of satiety. GIP is the main incretin hormone in healthy people, causative of most the incretin effects, but the insulin response after GIP secretion in type 2 diabetes mellitus (T2DM) is strongly reduced. Therefore, in the past GIP has been considered an unappealing therapeutic target for T2DM. This conception has been changing during recent years, since it has been reported that resistance to GIP can be reversed and its effectiveness restored by improving glycemic control. This fact paved the way for the development of a GIP receptor agonist-based therapy for T2DM, looking also for the possibility of finding a combined GLP-1/GIP receptor agonist. In this framework, the novel dual GIP and GLP-1 receptor agonist tirzepatide seems to be not just a new antidiabetic medication. Administered as a subcutaneous weekly injection, it is a manifold single pharmacological agent that has the ability to significantly lower glucose levels, as well as improve insulin sensitivity, reduce weight and amend dyslipidemia favorably modifying the lipid profile. Tirzepatide and additional dual GLP-1/GIP receptor agonists that could eventually be developed in the future seem to be a promising furthest advance for the management of several cardiometabolic settings. Obviously, it is too early to be overly hopeful since it is still necessary to determine the long-term effects of these compounds and properly verify the potential cardiovascular benefits. Anyway, we are currently facing a novel and very appealing therapeutic option.

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.

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

scholarly journals Effects of the Long-Acting Human Glucagon-Like Peptide-1 Analog Liraglutide on  -Cell Function in Normal Living Conditions

Diabetes Care ◽  
2007 ◽  
Vol 30 (8) ◽  
pp. 2032-2033 ◽  
Author(s):  
A. Mari ◽  
K. Degn ◽  
B. Brock ◽  
J. Rungby ◽  
E. Ferrannini ◽  
...  
Keyword(s):  
Cell Function ◽  
Living Conditions ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Long Acting
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