Pancreatic amylin and calcitonin gene-related peptide cause resistance to insulin in skeletal muscle in vitro

Nature ◽  
1988 ◽  
Vol 335 (6191) ◽  
pp. 632-635 ◽  
Author(s):  
Brendan Leighton ◽  
Garth J. S. Cooper
Keyword(s):  
Skeletal Muscle ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Resistance To Insulin

scholarly journals The role of the sensory peptide calcitonin-gene-related peptide(s) in skeletal muscle carbohydrate metabolism: effects of capsaicin and resiniferatoxin

1995 ◽  
Vol 307 (3) ◽  
pp. 707-712 ◽  
Author(s):  
B Leighton ◽  
E A Foot
Keyword(s):  
Skeletal Muscle ◽  
Soleus Muscle ◽  
Glycogen Synthesis ◽  
Calcitonin Gene Related Peptide ◽  
Sensory Nerves ◽  
Muscle Fibres ◽  
Related Peptide ◽  
Calcitonin Gene

1. The content of calcitonin-gene-related-peptide-like immunoreactivity (CGRP-LI) in various rat muscles was measured. Starvation for 24 h did not affect the content of CGRP-LI in these muscles, except for a decreased level in the starved-rat diaphragm. Higher contents of CGRP-LI were observed in well-vascularized muscles. 2. Capsaicin (at 1, 10 and 100 microM) inhibited insulin-stimulated rates of glycogen synthesis in isolated stripped incubated soleus muscle preparations by a mechanism independent of catecholamine release, since the effects of capsaicin were not altered by the beta-adrenoreceptor antagonist DL-propranolol. 3. Resiniferatoxin (10 nM), which is a potent capsaicin agonist, also significantly inhibited the insulin-stimulated rate of glycogen synthesis. Furthermore, the concentration of resiniferatoxin required to inhibit glycogen synthesis was 100 times less than the concentration of capsaicin needed for the same effect. 4. Capsaicin (10 microM) decreased the content of CGRP-LI in isolated stripped incubated soleus muscle preparations by about 40%. 5. Neonatal treatment of rats with capsaicin, which causes de-afferentation of some sensory nerves such, we hypothesize, that CGRP can no longer be released to counteract the effects of insulin in vivo, caused increased rates of glycogen synthesis and increased glycogen content in stripped soleus muscle preparations in vitro when muscles were isolated from the adult rats. 6. These findings support the hypothesis that capsaicin and resiniferatoxin elicit an excitatory response on sensory nerves in skeletal muscle in vitro to cause the efferent release of CGRP. Consequently, CGRP is delivered to skeletal muscle fibres to inhibit insulin-stimulated glycogen synthesis. The role of CGRP in recovery of blood glucose levels during hypoglycaemia is discussed.

Tapentadol inhibits calcitonin gene-related peptide release from rat brainstem in vitro

Peptides ◽  
2014 ◽  
Vol 56 ◽  
pp. 8-13 ◽  
Author(s):  
Maria Cristina Greco ◽  
Lucia Lisi ◽  
Diego Currò ◽  
Pierluigi Navarra ◽  
Giuseppe Tringali
Keyword(s):  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Peptide Release ◽  
Rat Brainstem

Calcitonin gene-related peptide is a survival factor, inhibiting apoptosis in neonatal rat gubernaculum in vitro

2009 ◽  
Vol 44 (8) ◽  
pp. 1497-1501 ◽  
Author(s):  
Jessica J. Chan ◽  
Pam J. Farmer ◽  
Bridget R. Southwell ◽  
Magdy Sourial ◽  
John M. Hutson
Keyword(s):  
Calcitonin Gene Related Peptide ◽  
Neonatal Rat ◽  
Related Peptide ◽  
Survival Factor ◽  
Calcitonin Gene

scholarly journals Renal microvascular actions of calcitonin gene-related peptide

1998 ◽  
Vol 274 (6) ◽  
pp. F1078-F1085 ◽  
Author(s):  
Martina Reslerova ◽  
Rodger Loutzenhiser
Keyword(s):  
Angiotensin Ii ◽  
Rat Kidney ◽  
Elevated Pressure ◽  
Calcitonin Gene Related Peptide ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Renal Vasoconstriction ◽  
Related Peptide ◽  
Calcitonin Gene

Calcitonin gene-related peptide (CGRP) is a potent vasodilator that is suggested to act via ATP-sensitive K channels (KATP). In the present study, we examined the actions of CGRP on pressure- and angiotensin II-induced vasoconstriction, using the in vitro perfused hydronephrotic rat kidney. Elevated pressure (from 80 to 180 mmHg) and 0.1 nM angiotensin II elicited similar decreases in afferent diameter in this model. CGRP inhibited myogenic reactivity in a concentration-dependent manner, completely preventing pressure-induced constriction at 10 nM (95 ± 10% inhibition). These effects were partially attenuated by 10 μM glibenclamide (62 ± 16% inhibition, P = 0.025), indicating both KATP-dependent and -independent actions of CGRP. In contrast, 10 nM CGRP inhibited angiotensin II-induced vasoconstriction by only 54 ± 11%, and this action was not affected by glibenclamide (41 ± 11%, P = 0.31). CGRP also inhibited the efferent arteriolar response to angiotensin II in the absence and presence of glibenclamide. Pinacidil (1.0 μM), a KATP opener also preferentially inhibited pressure- vs. angiotensin II-induced vasoconstriction (97 ± 5 and 59 ± 13% inhibition, respectively; P = 0.034). We conclude that the renal vasodilatory mechanisms of CGRP are pleiotropic and involve both KATP-dependent and -independent pathways. The effectiveness of CGRP in opposing renal vasoconstriction and the role of KATP in this action appear to depend on the nature the underlying vasoconstriction. We suggest that this phenomenon reflects an inhibition of KATP activation by angiotensin II.

Reversal of nerve damage in streptozotocin-diabetic rats by acute application of insulin in vitro

1988 ◽  
Vol 75 (6) ◽  
pp. 629-635 ◽  
Author(s):  
Geoffrey Burnstock ◽  
Rhona Mirsky ◽  
Abebech Belai
Keyword(s):  
Vasoactive Intestinal Polypeptide ◽  
Calcitonin Gene Related Peptide ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Rat Ileum ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Enteric Nerves ◽  
Intestinal Polypeptide

1. Immunohistochemical, immunoblotting and release experiments were performed on ileum from control rats, from 8-week streptozotocin-diabetic rats and from diabetic rats after acute application of insulin in vitro. 2. There was an increase in vasoactive-intestinal-polypeptide-like and a decrease in calcitonin-gene-related-peptide-like immunoreactivity in the myenteric plexus of the diabetic rat ileum, although electrically evoked release of both peptides from enteric nerves was defective. Acute application of insulin in vitro reversed the defective release and changes in immunoreactivity of vasoactive intestinal polypeptide and calcitonin-gene-related peptide seen in the enteric nerves of streptozotocin-diabetic rat ileum. 3. In addition, using a monoclonal neurofilament antibody RT 97 that recognizes a phosphorylated neurofilament epitope present in normal enteric nerves, it was shown that this phosphorylated neurofilament epitope was absent in diabetic nerves, even though a polyclonal neurofilament antibody revealed that neurofilaments were present in both axons and cell bodies of the myenteric plexus of diabetic rat ileum. After only 2 h of insulin incubation in vitro, the phosphorylated neurofilament epitope was again present in the nerves. 4. It is suggested that the abnormal distribution of phosphorylated neurofilaments and defective storage and release of vasoactive intestinal polypeptide and calcitonin-gene-related peptide in the present study may be a more general feature of diabetes. The restoration of these abnormalities by continuous acute insulin application in vitro shown here suggests that the availability of a steady level of insulin might prevent some of the changes which occur in early stages of diabetes. If so, this could influence the use of insulin in the treatment of diabetes, particularly in view of the recent report that short-term continuous subcutaneous insulin infusion restores the function of the autonomic and peripheral nerves in type I diabetic patients [Krönert, K., Hülsen, J., Luft, D., Stetter, T. & Eggstein, M. (1987) Journal of Clinical Endocrinology and Metabolism, 64, 1219–1223].

scholarly journals Cross-reactivity of amylin with calcitonin-gene-related peptide binding sites in rat liver and skeletal muscle membranes

1991 ◽  
Vol 277 (1) ◽  
pp. 139-143 ◽  
Author(s):  
A Chantry ◽  
B Leighton ◽  
A J Day
Keyword(s):  
Skeletal Muscle ◽  
Binding Site ◽  
Rat Liver ◽  
Specific Binding ◽  
Calcitonin Gene Related Peptide ◽  
Cross Reactivity ◽  
Scatchard Analysis ◽  
Human Calcitonin ◽  
Related Peptide ◽  
Calcitonin Gene

This study examines whether the high degree of sequence identity between amylin and calcitonin-gene-related peptide (CGRP) is reflected in their cross-reactivity at the level of membrane receptor binding. Rat liver plasma membranes contain a specific saturable binding site for 125I-labelled human CGRP-1. Binding reached equilibrium within 30 min and was rapidly reversed by re-incubating membranes in the presence of 1 microM human CGRP. In addition, the presence of 50 mM- or 500 mM-NaCl lowered specific binding by 30% and 77% respectively. Scatchard analysis was consistent with a single high-affinity site with a dissociation constant (Kd) of 0.125 nM and binding capacity (Bmax.) of 580 fmol/mg of membrane protein. Specific binding of 125I-labelled human CGRP-1 to both liver and skeletal muscle membranes was inhibited by human CGRP-1 [IC50 (concn. causing half-maximal inhibition of binding) 0.1-0.3 nM], and rat amylin (IC50 10 nM), but not by human calcitonin. Covalent cross-linking of 125I-CGRP to its binding site in rat skeletal muscle and liver membranes resulted in labelling of a major species of about 70 kDa under reducing conditions and about 55 kDa under alkylating conditions, as visualized on SDS/PAGE. These radiolabelled species were absent in the presence of CGRP or amylin at 1 microM. These results are indicative of a common binding site for both CGRP and amylin in liver and skeletal muscle, and it is suggested that both peptides mediate their actions through the same effector system. The normal physiological importance and the relevance to the pathology of type 2 diabetes of these data are discussed.

Flupirtine inhibits calcitonin-gene related peptide release from rat brainstem in vitro

2012 ◽  
Vol 506 (2) ◽  
pp. 332-335 ◽  
Author(s):  
Giuseppe Tringali ◽  
Maria Cristina Greco ◽  
Alessandro Capuano ◽  
Giuseppe Guerriero ◽  
Diego Currò ◽  
...  
Keyword(s):  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Peptide Release ◽  
Rat Brainstem
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