scholarly journals Specialized insulin is used for chemical warfare by fish-hunting cone snails

2015 ◽  
Vol 112 (6) ◽  
pp. 1743-1748 ◽  
Author(s):  
Helena Safavi-Hemami ◽  
Joanna Gajewiak ◽  
Santhosh Karanth ◽  
Samuel D. Robinson ◽  
Beatrix Ueberheide ◽  
...  

More than 100 species of venomous cone snails (genus Conus) are highly effective predators of fish. The vast majority of venom components identified and functionally characterized to date are neurotoxins specifically targeted to receptors, ion channels, and transporters in the nervous system of prey, predators, or competitors. Here we describe a venom component targeting energy metabolism, a radically different mechanism. Two fish-hunting cone snails, Conus geographus and Conus tulipa, have evolved specialized insulins that are expressed as major components of their venoms. These insulins are distinctive in having much greater similarity to fish insulins than to the molluscan hormone and are unique in that posttranslational modifications characteristic of conotoxins (hydroxyproline, γ-carboxyglutamate) are present. When injected into fish, the venom insulin elicits hypoglycemic shock, a condition characterized by dangerously low blood glucose. Our evidence suggests that insulin is specifically used as a weapon for prey capture by a subset of fish-hunting cone snails that use a net strategy to capture prey. Insulin appears to be a component of the nirvana cabal, a toxin combination in these venoms that is released into the water to disorient schools of small fish, making them easier to engulf with the snail’s distended false mouth, which functions as a net. If an entire school of fish simultaneously experiences hypoglycemic shock, this should directly facilitate capture by the predatory snail.

Author(s):  
Stefan Gründer

Acid-sensing ion channels (ASICs) are proton-gated Na+ channels. Being almost ubiquitously present in neurons of the vertebrate nervous system, their precise function remained obscure for a long time. Various animal toxins that bind to ASICs with high affinity and specificity have been tremendously helpful in uncovering the role of ASICs. We now know that they contribute to synaptic transmission at excitatory synapses as well as to sensing metabolic acidosis and nociception. Moreover, detailed characterization of mouse models uncovered an unanticipated role of ASICs in disorders of the nervous system like stroke, multiple sclerosis, and pathological pain. This review provides an overview on the expression, structure, and pharmacology of ASICs plus a summary of what is known and what is still unknown about their physiological functions and their roles in diseases.


2010 ◽  
Vol 298 (5) ◽  
pp. E1088-E1096 ◽  
Author(s):  
Diego Pérez-Tilve ◽  
Lucas González-Matías ◽  
Benedikt A. Aulinger ◽  
Mayte Alvarez-Crespo ◽  
Manuel Gil-Lozano ◽  
...  

Exendin-4 (Ex-4), an agonist of the glucagon-like peptide-1 receptor (GLP-1R), shares many of the actions of GLP-1 on pancreatic islets, the central nervous system (CNS), and the gastrointestinal tract that mediates glucose homeostasis and food intake. Because Ex-4 has a much longer plasma half-life than GLP-1, it is an effective drug for reducing blood glucose levels in patients with type 2 diabetes mellitus (T2DM). Here, we report that acute administration of Ex-4, in relatively high doses, into either the peripheral circulation or the CNS, paradoxically increased blood glucose levels in rats. This effect was independent of the insulinotropic and hypothalamic-pituitary-adrenal activating actions of Ex-4 and could be blocked by a GLP-1R antagonist. Comparable doses of GLP-1 did not induce hyperglycemia, even when protected from rapid metabolism by a dipeptidyl peptidase IV inhibitor. Acute hyperglycemia induced by Ex-4 was blocked by hexamethonium, guanethidine, and adrenal medullectomy, indicating that this effect was mediated by sympathetic nervous system (SNS) activation. The potency of Ex-4 to elevate blood glucose waned with chronic administration such that after 6 days the familiar actions of Ex-4 to improve glucose tolerance were evident. These findings indicate that, in rats, high doses of Ex-4 activate a SNS response that can overcome the expected benefits of this peptide on glucose metabolism and actually raise blood glucose. These results have important implications for the design and interpretation of studies using Ex-4 in rats. Moreover, since there are many similarities in the response of the GLP-1R system across mammalian species, it is important to consider whether there is acute activation of the SNS by Ex-4 in humans.


1995 ◽  
Vol 198 (5) ◽  
pp. 1161-1171 ◽  
Author(s):  
P Wainwright ◽  
B Richard

We present the first analysis of scaling effects on the motor pattern of a feeding vertebrate. Data are presented for the effects of body size on the pattern of activity in four head muscles during prey capture in the largemouth bass, Micropterus salmoides. Electromyographic (EMG) recordings were made from three expansive-phase muscles (the epaxialis, the sternohyoideus and the levator arcus palatini) and one compressive-phase muscle (the adductor mandibulae), during the capture of small fish prey. Recordings were made of 181 prey-capture events from 19 bass that ranged in size from 83 to 289 mm standard length. We measured seven variables from the myogram of each capture to quantify the temporal pattern of muscle activation, including the duration of activity in each muscle and the onset time of each muscle, relative to the onset of the sternohyoideus muscle. Regressions of the mean value of each variable for the 19 individuals on standard length revealed that only the onset time of the adductor mandibulae changed with fish body size. The increase in onset time of the adductor muscle appears to reflect the longer time taken to open the mouth fully in larger fish. Other research shows that the kinematics of the strike in this species slows significantly with increasing body size. The combined results indicate that the duration of the EMG signal is not directly correlated with the duration of force production in muscles when compared between fish of different sizes. The lack of scaling of burst duration variables suggests that the reduced speeds of prey-capture motion are explained not by changes in the envelope of muscle activity, but rather by the effects of scale on muscle contractile kinetics. These scaling effects may include changes in the relative resistance of the jaw and head structures to movement through water and changes in the intrinsic contractile properties of the muscles of the feeding apparatus.


2018 ◽  
Vol 38 (12) ◽  
pp. 3081-3091 ◽  
Author(s):  
Jan Kubanek ◽  
Poojan Shukla ◽  
Alakananda Das ◽  
Stephen A. Baccus ◽  
Miriam B. Goodman

PEDIATRICS ◽  
1976 ◽  
Vol 58 (1) ◽  
pp. 18-22
Author(s):  
Richard de Leeuw ◽  
Ivan J. de Vries

In 24% (18 out of 76) small-for-dates a "significant" though asymptomatic hypoglycemia was demonstrated during the first six hours of life. The cord blood glucose concentration was lower in the hypoglycemic compared to that of the small-for-date normoglycemic group. In the hypoglycemic infants, the disappearance rate of glucose was significantly elevated and the lipid mobilization disturbed. It is suggested that a lack of lipids for energy metabolism increases the glucose expenditure and hence increases the risk for hypoglycemia.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mriga Dutt ◽  
Jean Giacomotto ◽  
Lotten Ragnarsson ◽  
Åsa Andersson ◽  
Andreas Brust ◽  
...  

AbstractCone snails use separately evolved venoms for prey capture and defence. While most use a harpoon for prey capture, the Gastridium clade that includes the well-studied Conus geographus and Conus tulipa, have developed a net hunting strategy to catch fish. This unique feeding behaviour requires secretion of “nirvana cabal” peptides to dampen the escape response of targeted fish allowing for their capture directly by mouth. However, the active components of the nirvana cabal remain poorly defined. In this study, we evaluated the behavioural effects of likely nirvana cabal peptides on the teleost model, Danio rerio (zebrafish). Surprisingly, the conantokins (NMDA receptor antagonists) and/or conopressins (vasopressin receptor agonists and antagonists) found in C. geographus and C. tulipa venom failed to produce a nirvana cabal-like effect in zebrafish. In contrast, low concentrations of the non-competitive adrenoceptor antagonist ρ-TIA found in C. tulipa venom (EC50 = 190 nM) dramatically reduced the escape response of zebrafish larvae when added directly to aquarium water. ρ-TIA inhibited the zebrafish α1-adrenoceptor, confirming ρ-TIA has the potential to reverse the known stimulating effects of norepinephrine on fish behaviour. ρ-TIA may act alone and not as part of a cabal, since it did not synergise with conopressins and/or conantokins. This study highlights the importance of using ecologically relevant animal behaviour models to decipher the complex neurobiology underlying the prey capture and defensive strategies of cone snails.


2020 ◽  
Vol 318 (3) ◽  
pp. F531-F543 ◽  
Author(s):  
Marcelo D. Carattino ◽  
Nicolas Montalbetti

Acid-sensing ion channels (ASICs) are cation-permeable channels that in the periphery are primarily expressed in sensory neurons that innervate tissues and organs. Soon after the cloning of the ASIC subunits, almost 20 yr ago, investigators began to use genetically modified mice to assess the role of these channels in physiological processes. These studies provide critical insights about the participation of ASICs in sensory processes, including mechanotransduction, chemoreception, and nociception. Here, we provide an extensive assessment of these findings and discuss the current gaps in knowledge with regard to the functions of ASICs in the peripheral nervous system.


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