Exendin-4

Exendin‑4 (Exenatide) is an orally active, blood-brain barrier-permeable glucagon-like peptide-1 receptor (GLP‑1 receptor) agonist that resists degradation mediated by dipeptidyl peptidase IV. Exendin‑4 mediates multiple glucose-regulating effects, including stimulation of glucose-dependent insulin secretion, inhibition of glucagon production, increase in β-cell mass, delay of gastric emptying, reduction of food intake, improvement of peripheral insulin sensitivity, and restoration of normal islet structure. Exendin‑4 inhibits oxidative stress, alleviates inflammatory responses, and reduces neuronal apoptosis. Exendin‑4 reduces the aggregation level of mutant huntingtin, improves motor function, prolongs survival time, and regulates the expression levels of leptin and ghrelin. Exendin‑4 can be used in research related to type 2 diabetes, acute ischemic stroke, and Huntington's disease^[1][2][3]. In Vitro:Exendin-4 binds to and activates human and rat GLP-1 receptors with affinity and potency comparable to those of GLP-1; it directly enhances glucose-stimulated insulin secretion in vitro from islets isolated from male Lewis rats; it induces the differentiation of AR42J pancreatic acinar cells into insulin-, pancreatic polypeptide- and glucagon-positive cells^[1].
Exendin-4 inhibits apoptosis induced by pro-apoptotic cytokines by an average of 44% in FACS-purified rat β cells^[1].
Exendin-4 enhances the sensitivity of differentiated 3T3-L1 adipocytes to insulin-dependent glucose uptake; it increases insulin secretion by confluent nestin-positive islet-derived progenitor cells by 2 to 3-fold^[1]. In Vivo:Exendin-4 (100 μg/kg; i.p.; once daily; 12-13 weeks) reduces fasting blood glucose in diabetic db/db mice and decreases A1C by 47%, with similar beneficial effects observed in non-diabetic mice^[1].
Exendin-4 (administered via intraperitoneal injection at doses ranging from 0.1 μg to 100 μg per rat, twice daily for 5-6 weeks) reduces A1C by 41.3% and improves insulin sensitivity by 76% in obese diabetic ZDF rats; dose-dependent benefits are observed even at a dose of 0.1 μg per rat administered twice daily for 6 weeks^[1].
Exendin-4 (100 μg/kg; subcutaneous injection; single administration) produces a maximum 37% reduction in plasma glucose levels in fasted diabetic rhesus monkeys, with an ED₅₀ of 0.25 μg/kg^[1].
Exendin-4 (0.4 nmol/kg; intravenous injection; single administration) exhibits potent glucose-dependent insulinotropic activity in fasted Wistar rats, with an ED₅₀ of 0.014 nmol/kg^[1].
Exendin-4 (i.p.; once daily; for 10 consecutive days at a dose of 1 nmol/kg) attenuates the progression of diabetes in pancreatectomized rats, reduces their blood glucose levels by 40% compared with untreated rats, and increases β-cell mass by 40% via β-cell differentiation and proliferation^[1].
Exendin-4 (3 μg/kg/day; subcutaneous injection; once daily; postnatal days 2-6) increases pancreatic insulin content and β-cell mass in newborn prediabetic GK rats on postnatal day 7, and reduces fasting blood glucose levels at 2 months of age^[1].
Exendin-4 (3 μg/kg; i.p.; once daily; postnatal days 2-6) increases the β-cell mass of neonatal Wistar rats treated with Streptozotocin (HY-13753) to 71% of the healthy level on day 7^[1].
Exendin-4 (intraperitoneal injection, once daily, on postnatal days 1-6, at a dose of 1 nmol/kg) prevents impaired glucose tolerance in neonatal rats with intrauterine growth restriction (IUGR), maintains their normal fasting blood glucose levels and β-cell mass until 8 months after birth, and restores β-cell proliferation capacity and PDX-1 expression to normal levels^[1].
Exendin-4 (100 μg/kg, subcutaneous injection, twice daily for 15 consecutive days) reduces blood glucose levels in diabetic db/db mice by promoting β-cell proliferation, and increases their β-cell mass by 30%-60%^[1].
Exendin-4 (1 nmol/kg; i.p.; once daily; for 2 weeks) reduces fasting blood glucose levels, improves oral glucose tolerance, and increases β-cell mass by 1.4-fold in diabetic db/db mice^[1].
Exendin-4 (100 pmol/kg-1 nmol/kg; i.p.; once daily; for 2 consecutive weeks) reduces blood glucose levels in both healthy and diabetic mice, increases insulin secretion, lowers A1C levels by 20%-45%, and promotes β-cell neogenesis and PDX-1 expression in normoglycemic mice^[1].
Exendin-4 (24 nmol/kg; i.p.; once daily; initiated 2 days before Streptozotocin injection and continued until 3 days after injection) reduces the β-cell apoptosis rate by 76% in C57Bl/6 mice, decreases blood glucose levels, and maintains high plasma insulin levels for up to 55 days after Streptozotocin injection^[1].
Exendin-4 (0.1-100 μg; i.p.; twice daily; for 6 weeks) dose-dependently reduces food intake (ED₅₀ 0.14 μg) and body weight (ED₅₀ 0.42 μg) in obese diabetic Zucker rats, and sustained benefits for glycemic control and fat deposition are observed over a 56-day treatment period^[1].
Exendin-4 (10 μg; administered via tail vein; single dose; administered immediately after reperfusion) reduces cerebral infarction volume by approximately 47% in male C57BL/6 mice with ischemic stroke at 24 h, improves neurological function, inhibits oxidative stress and inflammatory responses, reduces cell death, and increases intracellular cyclic AMP and phosphorylated CREB levels^[2].
Exendin-4 (0.1 μM; subcutaneous injection; daily administration; throughout the entire study period) restores glycemic control, ameliorates pancreatic and brain pathology, enhances motor function, and increases survival rate by 18% in mouse models of Huntington's disease, while inducing moderate blood glucose reduction and motor function improvement in wild-type mice^[3].