37
Cone snails appear to have much to offer for new discoveries. Two drug companies in
Australia have begun developing snail peptide-based (conopeptide) analgesics from two
different cone snail species.20
Exenatide
Endocrinologist Dr. John Eng and other researchers followed up on earlier work by US
National Institutes of Health scientists and Sweden’s Karolinska Institute in the late 1970s
and early 1980s on new hormones that play a role in digestive and metabolic processes.
Efforts focused on a number of recently discovered peptides, their purpose and the loca-
tion of the body’s hormone receptors. Dr. Eng, who modestly calls himself a self-taught
biochemist, developed an assay based upon a chemical marker to screen for novel pep-
tides. Using his assay on a sample of dried Gila monster saliva, he observed two peaks of
concentrated activity. The Gila monster was chosen because of previous reports that its
bite caused the victims to develop pancreatitis (the venom caused over-stimulation of the
pancreas). When Dr. Eng determined the structure of the peptides responsible, he discov-
ered that one of the peaks contained a new peptide hormone he named exendin-4, now
known as exenatide.21 He found that exendin-4 had important glucose-lowering effects
and shared many of the same properties as glucagon-like peptide-1, a gut hormone that
plays an important role in regulating glucose.
Exenatide has been shown to inhibit gastric emptying and food intake and to con-
trol blood glucose levels. It is described as an incretin mimetic because it resembles the
antidiabetic or glucose lowering actions of naturally occurring human hormones called
incretins. These actions include stimulating the body’s ability to produce insulin in
response to elevated levels of blood sugar, inhibiting the release of glucagon following
meals, slowing the bloodstream absorbtion rate of nutrients and reducing food intake.
Exenatide is indicated as adjunctive therapy to improve glycemic control in patients with
type 2 diabetes mellitus who are taking metformin, a sulfonylurea, or a combination of
metformin and a sulfonylurea, but have not achieved adequate glycemic control.
A total of 1,494 patients with type 2 diabetes have been treated with BYETTA
(exenatide injection) in short- and long-term controlled clinical trials, and in long-term
open-label clinical trials.
Nonclinical studies have shown that exenatide is predominantly eliminated by
glomerular filtration with subsequent proteolytic degradation. The mean apparent clear-
ance of exenatide in humans is 9.1 L/h and the mean terminal half-life is 2.4 hours. These
pharmacokinetic characteristics of exenatide are independent of dose. In most individuals,
exenatide concentrations are measurable for approximately 10 hours post dose.22
According to the drug’s patient information sheet, it can cause low blood sugar when
used with a medicine that contains a sulfonylurea thus, the sulfonylurea dose may need
to be reduced. Exenatide is injected twice daily, at any time within one hour before morn-
ing and evening meals. It should not be used after meals. Too much of the drug can cause
nausea, vomiting, dizziness or symptoms of low blood sugar. In this instance, the patient
should contact a healthcare professional or the poison control center as soon as possible.
The Future
A recent article in The New York Times23 reconfirms the fact that current efforts to decipher
snake venom evolution will lead to new medical breakthroughs. This entails identify-
ing all the genes active in venom gland cells and reading the DNA sequence. There is no
lack of material to examine. It has been estimated that there are 1,200 poisonous marine
organisms, 700 poisonous fish and 400 venomous snakes. If that is not enough, scientists
also can examine 60 species of ticks, 75 kinds of scorpions, 750 poisons in more than 1,000
plant species and several birds whose feathers are toxic when touched or ingested.24
Venoms and Toxins
Cone snails appear to have much to offer for new discoveries. Two drug companies in
Australia have begun developing snail peptide-based (conopeptide) analgesics from two
different cone snail species.20
Exenatide
Endocrinologist Dr. John Eng and other researchers followed up on earlier work by US
National Institutes of Health scientists and Sweden’s Karolinska Institute in the late 1970s
and early 1980s on new hormones that play a role in digestive and metabolic processes.
Efforts focused on a number of recently discovered peptides, their purpose and the loca-
tion of the body’s hormone receptors. Dr. Eng, who modestly calls himself a self-taught
biochemist, developed an assay based upon a chemical marker to screen for novel pep-
tides. Using his assay on a sample of dried Gila monster saliva, he observed two peaks of
concentrated activity. The Gila monster was chosen because of previous reports that its
bite caused the victims to develop pancreatitis (the venom caused over-stimulation of the
pancreas). When Dr. Eng determined the structure of the peptides responsible, he discov-
ered that one of the peaks contained a new peptide hormone he named exendin-4, now
known as exenatide.21 He found that exendin-4 had important glucose-lowering effects
and shared many of the same properties as glucagon-like peptide-1, a gut hormone that
plays an important role in regulating glucose.
Exenatide has been shown to inhibit gastric emptying and food intake and to con-
trol blood glucose levels. It is described as an incretin mimetic because it resembles the
antidiabetic or glucose lowering actions of naturally occurring human hormones called
incretins. These actions include stimulating the body’s ability to produce insulin in
response to elevated levels of blood sugar, inhibiting the release of glucagon following
meals, slowing the bloodstream absorbtion rate of nutrients and reducing food intake.
Exenatide is indicated as adjunctive therapy to improve glycemic control in patients with
type 2 diabetes mellitus who are taking metformin, a sulfonylurea, or a combination of
metformin and a sulfonylurea, but have not achieved adequate glycemic control.
A total of 1,494 patients with type 2 diabetes have been treated with BYETTA
(exenatide injection) in short- and long-term controlled clinical trials, and in long-term
open-label clinical trials.
Nonclinical studies have shown that exenatide is predominantly eliminated by
glomerular filtration with subsequent proteolytic degradation. The mean apparent clear-
ance of exenatide in humans is 9.1 L/h and the mean terminal half-life is 2.4 hours. These
pharmacokinetic characteristics of exenatide are independent of dose. In most individuals,
exenatide concentrations are measurable for approximately 10 hours post dose.22
According to the drug’s patient information sheet, it can cause low blood sugar when
used with a medicine that contains a sulfonylurea thus, the sulfonylurea dose may need
to be reduced. Exenatide is injected twice daily, at any time within one hour before morn-
ing and evening meals. It should not be used after meals. Too much of the drug can cause
nausea, vomiting, dizziness or symptoms of low blood sugar. In this instance, the patient
should contact a healthcare professional or the poison control center as soon as possible.
The Future
A recent article in The New York Times23 reconfirms the fact that current efforts to decipher
snake venom evolution will lead to new medical breakthroughs. This entails identify-
ing all the genes active in venom gland cells and reading the DNA sequence. There is no
lack of material to examine. It has been estimated that there are 1,200 poisonous marine
organisms, 700 poisonous fish and 400 venomous snakes. If that is not enough, scientists
also can examine 60 species of ticks, 75 kinds of scorpions, 750 poisons in more than 1,000
plant species and several birds whose feathers are toxic when touched or ingested.24
Venoms and Toxins