Bioactive peptides from lizard venoms

Raufman, Jean‐Pierre

doi:10.1016/0167-0115(96)00135-8

Cited by 69 publications

(39 citation statements)

References 136 publications

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“…Furthermore, fatty acid derivatives of GLP-1 may also result in enhanced albumin binding and more prolonged bioactivity in vivo (36). The naturally occurring lizard exendin-4 peptide is not a substrate for DP IV and consequently exhibits a much longer half-life and greater potency in vivo (9,11,13).…”

Section: Discussionmentioning

confidence: 99%

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Sustained Expression of Exendin-4 Does Not Perturb Glucose Homeostasis, β-Cell Mass, or Food Intake in Metallothionein-Preproexendin Transgenic Mice

Baggio

Adatia

Bock

et al. 2000

Journal of Biological Chemistry

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Activation of glucagon-like peptide (GLP)-1 receptor signaling promotes glucose lowering via multiple mechanisms, including regulation of food intake, glucose-dependent insulin secretion, and stimulation of ␤-cell mass. As GLP-1 exhibits a short t1 ⁄2 in vivo, the biological consequences of prolonged GLP-1 receptor signaling remains unclear. To address this question, we have now generated metallothionein promoter-preproexendin (MT-Ex) transgenic mice. MT-Ex mice process preproexendin correctly, as is made evident by detection of circulating plasma exendin-4 immunoreactivity using high pressure liquid chromatography and an exendin-4-specific radioimmunoassay. Despite elevated levels of exendin-4, fasting plasma glucose and glucose clearance following oral and intraperitoneal glucose tolerance tests are normal in MT-Ex mice. Induction of transgene expression significantly reduced glycemic excursion during both oral and intraperitoneal glucose tolerance tests (p < 0.05) and increased levels of glucose-stimulated insulin following oral glucose administration (p < 0.05). Despite evidence that exendin-4 may induce ␤-cell proliferation, ␤-cell mass and islet histology were normal in MT-Ex mice. MT-Ex mice exhibited no differences in basal food intake or body weight; however, induction of exendin-4 expression was associated with reduced short term food ingestion (p < 0.05). In contrast, short term water intake was significantly reduced in the absence of zinc in fluid-restricted MT-Ex mice (p < 0.05). These findings illustrate that sustained elevation of circulating exendin-4 is not invariably associated with changes in glucose homeostasis, increased ␤-cell mass, or reduction in food intake in mice in vivo.Glucagon-like peptide-1 (GLP-1), 1 a product of the proglucagon gene, is released from gut endocrine cells and potentiates glucose-dependent insulin secretion (1). GLP-1 also regulates gastric emptying, food intake, glucagon secretion, and islet proliferation and hence is currently under investigation as a therapeutic agent for the treatment of diabetes (1). However, a significant limitation to potential GLP-1 therapy in diabetic subjects is the short biological half-life of this peptide (2-4), limiting its ability to control blood glucose for an extended period of time. These considerations have prompted investigation of strategies designed to prolong the duration of GLP-1 action in vivo (5, 6). Exendin-4, a peptide structurally related to but distinct from GLP-1 (7) was originally purified from the venom of a Heloderma suspectum lizard (8, 9). Subsequent characterization of exendin-4 activity demonstrated that the lizard peptide was a potent agonist for the mammalian glucagon-like peptide-1 receptor (GLP-1R) (8 -11). Exendin-4 exhibits a much longer in vivo half-life and prolonged duration of action (11), rendering it more potent for continuous stimulation of GLP-1 receptor signaling and sustained improvement in glucose homeostasis in vivo. Despite the structural homology of lizard exendin-4 and mammalian GLP-1, a ma...

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Section: Discussionmentioning

confidence: 99%

“…Exendin-4, a peptide structurally related to but distinct from GLP-1 (7) was originally purified from the venom of a Heloderma suspectum lizard (8,9). Subsequent characterization of exendin-4 activity demonstrated that the lizard peptide was a potent agonist for the mammalian glucagon-like peptide-1 receptor (GLP-1R) (8 -11).…”

mentioning

confidence: 99%

Sustained Expression of Exendin-4 Does Not Perturb Glucose Homeostasis, β-Cell Mass, or Food Intake in Metallothionein-Preproexendin Transgenic Mice

Baggio

Adatia

Bock

et al. 2000

Journal of Biological Chemistry

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“…Molecular cloning of bioactive polypeptide mRNAs from amphibian skin or reptile venom gland provides much useful information on endogenous propolypeptide convertase specifi cities, co-encoded peptides and can be a vital step in the initiation of studies designed to map genomic organization of respective genes [16,20]. Until now, whilst isolation and structural characterization of proteins/peptides could be achieved using lyophilized venom, construction of transcriptome cDNA and genomic DNA libraries for the purpose of molecular cloning of precursors and gene mapping, respectively, required the use of tissue samples that necessitated sacrifi ce of living specimens [25,26,27,28].…”

Section: Discussionmentioning

confidence: 99%

“…Despite intensive study of frog skin peptides and lizard peptides for several decades, the vast majority remain uncharacterized and the vast majority of amphibian species remain to be studied. The extraordinary complexity and diversity of frog skin and lizard venom peptides renders intriguing resources for novel drug lead discovery-a fact that is particularly relevant at present as interest in peptides as therapeutics undergoes a renaissance in the pharmaceutical industry [19,20]. In the past, the study of frog skin secretions and lizard venoms necessitated the sacrifi ce of the specimens and extraction of the dissected skin or venom gland, respectively.…”

Section: Introductionmentioning

confidence: 99%

DNA in Amphibian and Reptile Venom Permits Access to Genomes without Specimen Sacrifice

et al. 2008

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Amphibian defensive skin secretions and reptile venoms are rich sources of bioactive peptides with potential pharmacological/pharmaceutical applications. As amphibian and reptile populations are in rapid global decline, our research group has been developing analytical methods that permit generation of robust molecular data from non-invasive skin secretion samples and venom samples. While previously we have demonstrated that parallel proteome and venom gland transcriptome analyses can be performed on such samples, here we report the presence of DNA that facilitates the more widely-used applications of gene sequencing, such as molecular phylogenetics, in a non-invasive manner that circumvents specimen sacrifi ce. From this "surrogate" tissue, we acquired partial 12S and 16S rRNA gene sequences that are presented for illustration purposes. Thus from a single sample of amphibian skin secretion and reptile venom, robust and complementary proteome, transcriptome and genome data can be generated for applications in diverse scientifi c disciplines.

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“…Exendin 4I, a naturally occurring longacting GLP-1R agonist with a resistance to DPP-IV-mediated inactivation, is even more potent than the native GLP-1 [35] . The design of DPP-IV-resistant GLP-1-analogs, conjugated forms of GLP-1, as well as the DPP-IV inhibitors, have been explored by various research teams, and various agonists of the GLP-1R have been developed and tested in animal models of T2DM [6] .…”

Section: Synthesis and Secretion Of Glp-1mentioning

confidence: 99%

Is Glucagon-like peptide-1, an agent treating diabetes, a new hope for Alzheimer’s disease?

Lin

2007

Neurosci. Bull.

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Glucagon-like peptide-1 (GLP-1) has been endorsed as a promising and attractive agent in the treatment of type 2 diabetes mellitus (T2DM). Both Alzheimer's disease (AD) and T2DM share some common pathophysiologic hallmarks, such as amyloid β (Aβ), phosphoralation of tau protein, and glycogen synthase kinase-3. GLP-1 possesses neurotropic properties and can reduce amyloid protein levels in the brain. Based on extensive studies during the past decades, the understanding on AD leads us to believe that the primary targets in AD are the Aβ and tau protein. Combine these findings, GLP-1 is probably a promising agent in the therapy of AD. This review was focused on the biochemistry and physiology of GLP-1, communities between T2DM and AD, new progresses of GLP -1 in treating T2MD and improving some pathologic hallmarks of AD.

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Bioactive peptides from lizard venoms

Cited by 69 publications

References 136 publications

Sustained Expression of Exendin-4 Does Not Perturb Glucose Homeostasis, β-Cell Mass, or Food Intake in Metallothionein-Preproexendin Transgenic Mice

Sustained Expression of Exendin-4 Does Not Perturb Glucose Homeostasis, β-Cell Mass, or Food Intake in Metallothionein-Preproexendin Transgenic Mice

DNA in Amphibian and Reptile Venom Permits Access to Genomes without Specimen Sacrifice

Is Glucagon-like peptide-1, an agent treating diabetes, a new hope for Alzheimer’s disease?

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