Gila monsters are meandering lizards with brilliant colourful beaded patterns. They may grow up to two feet in length and scavenge about in the desert for bird eggs and other easy prey. When provoked, they bite with surprisingly intense force, and release venom through grooved jaws into the wound.
Gila Saliva and Serum Glucose
The venomous saliva of Gila monsters is a soup of proteins and compounds with neurotoxic and inflammatory effects. One of the proteins acts as an incretin mimetic. Incretin, also known as GLP-1 (glucagon-like peptide-1) is produced by endocrine cells of the small intestine after food ingestion, and affects diet and blood sugar in several ways.
GLP-1 Impacts Human Digestion By
- Increasing insulin secretion in relation to serum levels of glucose
- Decreasing levels of glucagon – a hormone that raises serum glucose
- Delays gastric emptying to slow down digestion and decrease appetite
- Mild, prolonged appetite suppression due to action on hypothalamic receptors
Exenatide
The protein resembling GLP-1, found in Gila monsters is known as exendin-4. While GLP-1’s rapid and transient effect makes it unsuitable for use as a therapeutic treatment, exendin-4 is just different enough to have a sustained duration. This makes it useful as a treatment option for diabetes mellitus. A synthetic version of the protein has the scientific label “exenatide” and is marketed under the name “byetta.”
Positive Impact on Diabetes
Byetta was approved by the US FDA for treatment of unresponsive type II diabetes mellitus in 2005. It is dosed at 5-10 mcg/day in subcutaneous injection. While not approved for type I diabetes mellitus at this time, several studies point to positive effects in conjunction with other therapies. While many conventional therapies have a transient effect on hyperglycemia, byetta appears to have sustained efficacy in lowering body fat and modulating serum glucose levels.
Discouraging Reports of Adverse Effects
Concerns have emerged regarding risk of renal failure and pancreatitis with long term use. Several animal models have confirmed inflammation of pancreatic glandular cells with continual use, though the mechanism of this is still in discussion. At the first signs of pancreatitis this drug must be discontinued.
Another Step Along the Path
Use of GLP-1 analogues are still being explored but research has moved on to a new class of drugs that slow the breakdown of physiologic GLP-1. They do this by throwing a monkey wrench at the enzyme dipeptidyl peptidase IV (DPP-IV) that converts GLP-1 to an inactive form in the body. This leaves more physiological GLP-1 around to do the same thing as analogues but does not seem to have the same adverse effects. Proteins from Gila monster saliva were a key step in this process and many diabetics have them to thank for a novel treatment approach in the management of diabetes.
References
(2009). "Exenatide: renal failure. Risk-benefit balance becoming uncertain." Prescrire Int 18(101): 124.
Ayoub, W. A., A. A. Kumar, et al. (2009). "Exenatide Induced Acute Pancreatitis." Endocr Pract: 1-16.
Gentilella, R., C. Bianchi, et al. (2009). "Exenatide: a review from pharmacology to clinical practice." Diabetes Obes Metab 11(6): 544-56.
Nachnani, J. S., D. G. Bulchandani, et al. (2009). "Biochemical and histological effects of exendin-4 (exenatide) on the rat pancreas." Diabetologia.
Paisley, A. N., M. W. Savage, et al. (2009). "Stabilizing effect of exenatide in a patient with C-peptide-negative diabetes mellitus." Diabet Med 26(9): 935-8.
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