Exendin-4, a glucagon-like protein-1 (GLP-1) receptor agonist, mimics the activity of mammalian incretin hormone glucagon-like peptide 1 (GLP-1), and thus, promotes insulin secretion and functions in the control of glucose [1].
In vitro: Exendin-4 showed a pronounced effect on intracellular cAMP generation. Treatment of GLP-1 in combination with exendin-4 showed additive action on the generation of cAMP. In isolated rat islets and in mouse insulinoma beta TC-1 cells, Exendin-4 stimulated the glucose-induced insulin secretion in a dose dependent manner [2]. In basal forebrain cholinergic neurons, exendin-4 greatly reduced ibotenic acid-induced depletion of choline acetyltransferase immunoreactivity [3].
In vivo: In ob/ob mice, administration of Exendin-4 (10 μg/kg or 20 μg/kg) improved insulin sensitivity and significantly reduced serum glucose and hepatic steatosis. Exendin-4 appeared to effectively reverse hepatic steatosis in ob/ob mice by improving insulin sensitivity [1]. In athymic mice, 63% of exendin-4-treated mice achieved graft function compared with 21% of untreated mice (p = 0.033) in the short-term study. 88% of treated mice had functioning grafts compared with 22% of controls (p = 0.015) in the long-term study. Exendin-4-treated mice gained significantly more weight than the untreated counterparts [4].
References:
Ding X, Saxena N K, Lin S, et al.? Exendin‐4, a glucagon‐like protein‐1 (GLP‐1) receptor agonist, reverses hepatic steatosis in ob/ob mice[J]. Hepatology, 2006, 43(1): 173-181.
Gke R, Fehmann H C, Linn T, et al.? Exendin-4 is a high potency agonist and truncated exendin-(9-39)-amide an antagonist at the glucagon-like peptide 1-(7-36)-amide receptor of insulin-secreting beta-cells[J]. Journal of Biological Chemistry, 1993, 268(26): 19650-19655.
Perry T A, Haughey N J, Mattson M P, et al.? Protection and reversal of excitotoxic neuronal damage by glucagon-like peptide-1 and exendin-4[J]. Journal of Pharmacology and Experimental Therapeutics, 2002, 302(3): 881-888.
Sharma A, Srenby A, Wernerson A, et al.? Exendin-4 treatment improves metabolic control after rat islet transplantation to athymic mice with streptozotocin-induced diabetes[J]. Diabetologia, 2006, 49(6): 1247-1253.
