Jundong Zhang

Discovery and characterization of taspoglutide, a novel analogue of human glucagon-like peptide-1, engineered for sustained therapeutic activity in type 2 diabetes

Aim: Glucagon‐like peptide‐1 (GLP‐1) receptor agonists for the treatment of type 2 diabetes are administered by daily injection because of short plasma half‐lives, which result partly from the biochemical instability of these peptides. There is a medical need for GLP‐1 analogues that can be administered less frequently for patient convenience.

Effect of application route of the ghrelin analog BIM-28131 (RM-131) on body weight and body composition in a rat heart failure model

Chronic heart failure (CHF) remains one of the most challenging diseases in terms of numbers and disease management, particularly so, if the CHF patient develops cardiac cachexia. Ghrelin and its analogs have been suggested to improve body weight and cardiac function in heart failure models and exploratory human clinical studies. However, most ghrelin compounds are peptides and need to be injected several times per day, which affects the quality of life of patients. Here, we compared two application routes, three times daily subcutaneous (sc) injections to continuous infusion using osmotic mini-pumps in a rat model of CHF. Moreover, the effects were also compared to three times daily sc injections of growth hormone (GH). Rats were treated for 28 d. The results show that treatment with 50 or 100 nmol/kg/d BIM-28131 (RM-131) potently induces body weight gain, fat and lean mass compared to placebo. The gain of lean mass was equal to the gain of lean mass in the 2mg/kg/d GH group and superior to 250 μg/kg/d GH. Both GH and BIM-28131 increased levels of insulin-like growth factor-1 to a similar extent. Little effect was seen on cardiac function; only cardiac output was improved by either high dose BIM-28131 or GH. Overall the effects of BIM-28131 were similar in both application routes.

A GHS-1a Receptor Agonist that is Highly Effective in Stimulating Body Weight Gain

Introduction Ghrelin, a 28 amino acid octanoylated peptide, has been identified as an endogenous ligand for the growth hormone (GH) secretagogue (GHS) receptor [1]. In addition to stimulating GH secretion, ghrelin increases food intake and induces body weight gain [2]. Due to its unique biological effects on appetite and positive energy balance, ghrelin is considered as a viable target for developing therapeutic agents for the treatment of cachexic and anorexic disorders. In an effort to search for ghrelin analogs that are more suitable for therapeutic use, we have discovered a pentapeptide that has higher GHS-1a receptor binding affinity and longer plasma half-life than human ghrelin (h-ghrelin).