If you’ve followed this blog for a while or if your interest in body composition has risen to the level of more than mere passing interest, you’ve probably become quite familiar with the hormone insulin. But what about it’s alter-ego, or arch nemesis, Glucagon? Let’s learn about it’s cousin Glucagon Like Peptide 1.
Much like IGF-1, also known as Insulin-Like Growth Factor 1, there exists a peptide called Glucagon like peptide 1 that does some pretty rad stuff when it comes to fat loss. Only problem has been creating a peptide that can be absorbed and then stay around long enough to do its job once it’s in the body. So researchers set about to find out if there’s anything else, non-peptide based (to avoid absorption and utilization issues) that does the same thing (or more scientifically agonizes the same receptor) as GLP-1.
It looks like they’ve found it and so far it’s fancy name is Boc5.
PLoS One. 2010 Dec 3;5(12):e14205.
Reversal of obesity and insulin resistance by a non-peptidic glucagon-like Peptide-1 receptor agonist in diet-induced obese mice.
The National Center for Drug Screening, Shanghai, China.
BACKGROUND: Glucagon-like peptide-1 (GLP-1) is recognized as an important regulator of glucose homeostasis. Efforts to utilize GLP-1 mimetics in the treatment of diabetes have yielded clinical benefits. A major hurdle for an effective oral therapy has been the difficulty of finding a non-peptidic GLP-1 receptor (GLP-1R) agonist. While its oral bioavailability still poses significant challenges, Boc5, one of the first such compounds, has demonstrated the attainment of GLP-1R agonism in diabetic mice. The present work was to investigate whether subchronic Boc5 treatment can restore glycemic control and induce sustainable weight loss in diet-induced obese (DIO) mice, an animal model of human obesity and insulin resistance.
METHODOLOGY/PRINCIPAL FINDINGS: DIO mice were treated three times a week with Boc5 (0.3, 1 and 3 mg) for 12 weeks. Body weight, body mass index (BMI), food intake, fasting glucose, intraperitoneal glucose tolerance and insulin induced glucose clearance were monitored regularly throughout the treatment. Glucose-stimulated insulin secretion, β-cell mass, islet size, body composition, serum metabolic profiles, lipogenesis, lipolysis, adipose hypertrophy and lipid deposition in the liver and muscle were also measured after 12 weeks of dosing. Boc5 dose-dependently reduced body weight, BMI and food intake in DIO mice. These changes were associated with significant decreases in fat mass, adipocyte hypertrophy and peripheral tissue lipid accumulation. Boc5 treatment also restored glycemic control through marked improvement of insulin sensitivity and normalization of β-cell mass. Administration of Boc5 (3 mg) reduced basal but enhanced insulin-mediated glucose incorporation and noradrenaline-stimulated lipolysis in isolated adipocytes from obese mice. Furthermore, circulating leptin, adiponectin, triglyceride, total cholesterol, nonesterified fatty acid and high-density lipoprotein/low-density lipoprotein ratio were normalized to various extents by Boc5 treatment.
CONCLUSIONS/SIGNIFICANCE: Boc5 may produce metabolic benefits via multiple synergistic mechanisms and may represent an attractive tool for therapeutic intervention of obesity and diabetes, by means of non-peptidic GLP-1R agonism.
PMID: 21151924 [PubMed - in process]Free Article