Can modulation of gut derived hormones influence body weight and metabolism? If you recall from our previous discussion about incretin hormones, GLP-1 is the intestinal derived hormone that is released in response to ingested carbohydrates and fats (1). As you can see from the image to the right, GLP-1 is an important regulator of various physiological processes pertaining to metabolism and body composition, in and outside of the gastrointestinal tract. Such outside-the-gut effects include improved blood glucose and insulin signaling, increased glucose uptake in skeletal muscle, reduced appetite and increased satiety. All of which are beneficial effects.
Can loss of GI-metabolic signaling influence metabolic disease progression and development of obesity?
Several studies have found that following a meal, GLP-1 release is impaired in type 2 diabetic subjects (2,3). Impaired GLP-1 release leads to impairments in metabolism, insulin sensitivity and lipid storage. Researchers in Denmark have conducted an excellent review of the various aspects that influence GLP-1 release:
- Obese patients have impaired GLP-1 response when carbohydrates are ingested
- Poor glycemic control (elevated fasting glucose and increased HbA1C) are both associated with reduced GLP-1 signaling
- Decreased bile secretion is associated with reduced GLP-1 signaling
“..impairment of the incretin effect is a very early sign of impaired glucose metabolism that may be observed before other signs of β-cell dysfunction are apparent, but that is aggravated further when β-cell function is impaired.” Notes Dr. Jen Holst of University of Copenhagen
Are pharmacological GLP-1 receptor agonists ready for prime time?
Recent meta analyses indicate that administration of pharmacological agents designed to activate the GLP-1 receptor- exenatide and liraglutide, both increatin hormone receptor agnosists in overweight patients are associated with weight loss, reduced serum cholesterol and blood pressure (5,6). However, use of these medications are associated with hypoglycemia and various GI side effects.
What natural therapies can we use incorporate to improve GLP-1 signaling?
In my new book I discuss many natural therapies that can be utilized to improve metabolic signaling and body composition through modulation of the gut microflora and gut-endocrine signaling pathways.
1) Fineman, MS et al. GLP-1 Based Therapies: Differential Effects on Fasting and Postprandial Glucose. Diabetes, Obesity and Metabolism 2012. http://onlinelibrary.wiley.com/doi/10.1111/j.1463-1326.2012.01560.x/abstract
2) Toft-Nielsen MB, et al .Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. J Clin Endocrinol Metab 2001;86:3717–3723pmid:11502801 Abstract/FREE Full Text
3) Vilsbøll T et al. Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes 2001;50:609–613pmid:11246881Abstract/FREE Full Text
4) Jens Juul Holst, Medical Physiology at the Department of Biomedical Sciences at the faculty of Health Sciences, University of Copenhagen http://metabol.ku.dk/researchers/holst/
5) Kock, L. Pharmacotherapy: GLP-1R agonists—the new weapon against obesity? Nature Reviews Endocrinology (2012)
6) Vilsbøll, T. et al. Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. BMJ 344, d7771 (2012)