Reptile & Amphibian Forums

anyone studying this? Dr. Fry have you done any work here? Im thinking about theses I can work on with heloderms. Dan Beck is not taking on new students, so any profs out there who need grad students send me an email. I am hoping to start in the spring or summer.
Cheers
Brett
www.auntievenom.com

The peptide in Gila venom being developed to treat human diabetes is exendin-4 (drug name exenatide). This peptide is 50% homologous with the human hormone GLP-1 and acts on the GLP-1 receptor.

The analogous protein in horridum venom is exendin-3 (discovered before exendin-4). It is identical to exendin-4 except for a couple of amino acid substitutions. Its activity is somewhat different than that of exendin-4.

If you google exendin-3 and exendin-4 you will be able to see some the current (and past) research on these two peptides.

Mark
www.DrSeward.com

For those interested in some basic information on the drug Mark is referring to, here it is:

exenatide
Amylin, Lilly submitted for approval, USA (diabetes)
Amylin and Lilly reported on 30 June 2004 that an NDA has been submitted to the US FDA seeking approval of exenatide for the treatment of type II diabetes. The NDA included data on more than 1800 subjects treated with exenatide.

Exenatide is a synthetic form of exendin 4, a 39 amino acid peptide isolated from the salivary secretions of the Gila monster lizard.

Like Mark said, do a search and you'll find LOTS of information. This is truly groundbreaking stuff and I am anxious to see what else we discover with our venomous herps!

Rob Carmichael, Curator
The Wildlife Discovery Center at Elawa Farm
Lake Forest, IL

Lead Story from Drug News 23 July 2004
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>>The peptide in Gila venom being developed to treat human diabetes is exendin-4 (drug name exenatide). This peptide is 50% homologous with the human hormone GLP-1 and acts on the GLP-1 receptor.
>>
>>The analogous protein in horridum venom is exendin-3 (discovered before exendin-4). It is identical to exendin-4 except for a couple of amino acid substitutions. Its activity is somewhat different than that of exendin-4.
>>
>>If you google exendin-3 and exendin-4 you will be able to see some the current (and past) research on these two peptides.
>>
>>Mark
>>www.DrSeward.com
-----
Rob Carmichael, Curator
The Wildlife Discovery Center at Elawa Farm
Lake Forest, IL

Here is an abstract from the annual meeting of the American Diabetes Association from several years ago. It is the first research to suggest the actual role of exendin-4 in the Gila.

Young A, Petrella E, Blase E, Seward M. Exendin-4 is a circulating meal-related peptide in the Gila Monster (Heloderma suspectum). Diabetes. 1999;48:A425 (abstract 1880).

Exendin-4, a 39 amino acid peptide showing ~50% homology to mammalian glucagon-like peptide1 (GLP-1) has been reported to have certain antidiabetic activities similar to those of GLP1. Synthetic exendin-4 (AC2993) is under investigation for the treatment of diabetes because, unlike GLP-1, it has a markedly prolonged duration of glucose-lowering action. Exendin-4 was first isolated from the Gila monster lizard (Heloderma suspectum) and was thought to be a (potentially toxic) component of the venom. It now appears that exendin-4 is devoid of toxicity, and that it instead is made in salivary glands in the Gila monster. None of exendin4 s biological actions in mammals would suggest a purpose against the prey of the lizard (eggs and nestlings), but its potent anorectic and insulinotropic actions could indicate a feed-forward metabolic role in the lizard itself. Such a role would predict that exendin-4 appeared in the blood in response to feeding. To investigate this possibility, blood was sampled from one animal fasted for 7 weeks, before and 30 min after ingestion of a small rat. Plasma was assayed for full-length exendin-4 using an in-house immunoradiometric assay with monoclonal antibody pairs directed to epitopes at N- and C-termini of exendin4. Fasting plasma exendin-4 concentration was 76 pg/mL, near the lower limit of quantitation. After eating, this value rose 300-fold to 23,120 pg/mL. In a second experiment, serial samples were taken from two animals fasted 5 weeks before and after ingestion of 1 or 2 small rats (47-49 g). Plasma exendin-4 concentration rose 23- to 36-fold (to 4860, 8340 pg/mL) immediately after eating, perhaps consistent with a direct passage of exendin-4 from the salivary gland to blood. After eating a second rat (t=30 min), plasma exendin-4 concentration in one Gila rose further to 27,209 pg/mL. Plasma exendin-4 concentration decayed with a t1/2 of 5.00 and 5.33 hours, respectively. In conclusion, exendin-4, known to originate from the salivary gland of the Gila monster, appears in high concentration in the blood immediately after eating. It is possible that this may represent a meal-related signal to inhibit further eating and promote nutrient storage. If so, this would be the first example of the salivary gland exhibiting an endocrine function related to metabolic control.

www.DrSeward.com