Cell lines

Mouse insulinoma beta TC-1 cell line

Preparation method

Soluble to 1 mg/ml in sterile water. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

0.1 nM to 1 μM for 2 h

Applications

Exendin-4, like GLP-1, could stimulate dose dependently the glucose-induced insulin secretion in isolated rat islets, and, in mouse insulinoma beta TC-1 cells, both peptides were able to stimulate the proinsulin gene expression at the level of transcription.

Animal models

Ob/ob mice model

Dosage form

10 μg/kg or 20 μg/kg, qd for 14 days

Application

Ob/ob mice were treated with Exendin-4 [10 μg/kg or 20 μg/kg] for 60 days. It was found that Ob/ob mice sustained a reduction in the net weight gained during Exendin-4 treatment. Serum glucose and hepatic steatosis was significantly reduced in Exendin-4 treated ob/ob mice. Moreover, Exendin-4 improved insulin sensitivity in ob/ob mice, as calculated by the homeostasis model assessment. The measurement of thiobarbituric reactive substances as a marker of oxidative stress was significantly reduced in ob/ob-treated mice with Exendin-4.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

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.