Glucagon is conventionally regarded as a hormone, counter regulatory in function to insulin and plays a critical anti-hypoglycemic role by maintaining glucose homeostasis in both animals and humans. Glucagon performs this function by increasing hepatic glucose output to the blood by stimulating glycogenolysis and gluconeogenesis in response to starvation. Additionally it plays a homeostatic role by decreasing glycogenesis and glycolysis in tandem to try and maintain optimal glucose levels. To perform this action, it also increases energy expenditure which is contrary to what one would expect and has actions which are unique and not entirely in agreement with its role in protection from hypoglycemia. Interestingly, glucagon-like peptides (GLP-1 and GLP-2) from the major fragment of proglucagon (in non-mammalian vertebrates, as well as in mammals) may also modulate response to stress in addition to their other physiological actions. These unique modes of action occur in response to psychological, metabolic and other stress situations and mirror the role of adipokinetic hormones (AKHs) in insects which perform a similar function. The findings on the anti-stress roles of glucagon and glucagon-like peptides in mammalian and non-mammalian vertebrates may throw light on the multiple stress responsive mechanisms which operate in a concerted manner under regulation by AKH in insects thus functioning as a stress responsive hormone while also maintaining organismal homeostasis.

• MeSH
• AMP cyklický metabolismus   MeSH
• buněčná membrána metabolismus   MeSH
• energetický metabolismus MeSH
• glukagon metabolismus   MeSH
• glukagonu podobný peptid 1 metabolismus   MeSH
• glukagonu podobný peptid 2 metabolismus   MeSH
• hmyz metabolismus   fyziologie   MeSH
• hmyzí hormony metabolismus   MeSH
• kyselina pyrrolidonkarboxylová analogy a deriváty   metabolismus   MeSH
• lidé MeSH
• mozek metabolismus   fyziologie   MeSH
• neurony metabolismus   MeSH
• oligopeptidy metabolismus   MeSH
• oxidační stres * MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• adipokinetic hormone MeSH Prohlížeč
• AMP cyklický MeSH
• glukagon MeSH
• glukagonu podobný peptid 1 MeSH
• glukagonu podobný peptid 2 MeSH
• hmyzí hormony MeSH
• kyselina pyrrolidonkarboxylová MeSH
• oligopeptidy MeSH
• reaktivní formy kyslíku MeSH

Glucagon is actually used in the treatment of severe hypoglycemia. Due to technological difficulties with stability in solution, glucagon in currently available preparations was contained in a form of powder, which needs to be first dissolved in the water before application. This particular administration of glucagon was associated with a certain delay and several mistakes that decreased real amount of glucagon injected in the body. Currently two new formulas of glucagon appeared on the market - first as a stable liquid solution, second as a powder for nasal administration. This article summarizes currently available information about these preparations.

• Klíčová slova
• diabetes, glucagon, hypoglycemia, therapy, type 2 diabetes,
• MeSH
• aplikace intranazální MeSH
• diabetes mellitus 1. typu * MeSH
• glukagon terapeutické užití   MeSH
• hypoglykemie * chemicky indukované   farmakoterapie   MeSH
• inzulin terapeutické užití   MeSH
• krevní glukóza MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• glukagon MeSH
• inzulin MeSH
• krevní glukóza MeSH

Resembling the main function of insect adipokinetic hormones (AKHs), the vertebrate hormone glucagon mobilizes energy reserves and participates in the control of glucose level in the blood. Considering the similarities, the effect of porcine glucagon was evaluated in an insect model species, the firebug Pyrrhocoris apterus. Using the mouse anti-glucagon antibody, presence of immunoreactive material was demonstrated for the first time in the firebug CNS and gut by ELISA. Mammalian (porcine) glucagon injected into the adult bugs showed no effect on hemolymph lipid level or on the level of AKH in CNS and hemolymph, however, it activated an antioxidant response when oxidative stress was elicited by paraquat, a diquaternary derivative of 4, 4'-bipyridyl. Glucagon elicited the antioxidant response by increasing glutathione and decreasing protein carbonyl levels in hemolymph, decreasing both protein carbonyl and protein nitrotyrosine levels in CNS. Additionally, when co-injected with paraquat, glucagon partially eliminated oxidative stress markers elicited by this redox cycling agent and oxidative stressor. This indicates that glucagon might induce an antioxidant defense in insects, as recently described for AKH. Failure of glucagon to alter AKH level in the bug's body indicates employment of an independent pathway without involving the native AKH.

• MeSH
• antioxidancia farmakologie   MeSH
• centrální nervový systém účinky léků   imunologie   MeSH
• glukagon imunologie   farmakologie   MeSH
• Heteroptera účinky léků   metabolismus   MeSH
• krevní glukóza imunologie   MeSH
• oxidační stres účinky léků   imunologie   MeSH
• prasata * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antioxidancia MeSH
• glukagon MeSH
• krevní glukóza MeSH

Type B trichothecenes commonly contaminate cereal grains and include five structurally related congeners: deoxynivalenol (DON), 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), fusarenon X (FX), and nivalenol (NIV). These toxins are known to have negative effects on human and animal health, particularly affecting food intake. However, the pathophysiological basis for anorexic effect is not fully clarified. The purpose of this study is to explore the potential roles of the brain-gut peptides substance P (SP) and glucagon-like peptide-17-36 amide (GLP-1) in anorexic responses induced by type B trichothecenes following both intraperitoneal (IP) and oral administration. SP and GLP-1 were elevated at 1 or 2 h and returned to basal levels at 6 h following exposure to DON and both ADONs. FX induced the production of both brain gut peptides with initial time at 1 or 2 h and duration > 6 h. Similar to FX, exposing IP to NIV caused elevations of SP and GLP-1 at 1 h and lasted more than 6 h, whereas oral exposure to NIV only increased both brain gut peptides at 2 h. The neurokinin-1 receptor (NK-1R) antagonist Emend® dose-dependently attenuated both SP- and DON-induced anorexic responses. Pretreatment with the GLP-1 receptor (GLP-1R) antagonist Exending9-39 induced a dose-dependent attenuation of both GLP-1- and DON-induced anorexic responses. To summarize, the results suggest that both SP and GLP-1 play important roles in anorexia induction by type B trichothecenes.

• Klíčová slova
• anorexia, brain-gut peptide, glucagon-like peptide-17-36 amide, substance P, trichothecene,
• MeSH
• amidy toxicita   MeSH
• anorektika * toxicita   MeSH
• glukagonu podobný peptid 1 toxicita   MeSH
• lidé MeSH
• nechutenství chemicky indukované   MeSH
• substance P toxicita   MeSH
• trichotheceny typu B * MeSH
• trichotheceny * toxicita   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 15-acetyldeoxynivalenol MeSH Prohlížeč
• 3-acetyldeoxynivalenol MeSH Prohlížeč
• amidy MeSH
• anorektika * MeSH
• deoxynivalenol MeSH Prohlížeč
• fusarenon-X MeSH Prohlížeč
• glukagonu podobný peptid 1 MeSH
• nivalenol MeSH Prohlížeč
• substance P MeSH
• trichothecene MeSH Prohlížeč
• trichotheceny typu B * MeSH
• trichotheceny * MeSH

The physical stability of peptide-based drugs is of great interest to the pharmaceutical industry. Glucagon-like peptide 1 (GLP-1) is a 31-amino acid peptide hormone, the analogs of which are frequently used in the treatment of type 2 diabetes. We investigated the physical stability of GLP-1 and its C-terminal amide derivative, GLP-1-Am, both of which aggregate into amyloid fibrils. While off-pathway oligomers have been proposed to explain the unusual aggregation kinetics observed previously for GLP-1 under specific conditions, these oligomers have not been studied in any detail. Such states are important as they may represent potential sources of cytotoxicity and immunogenicity. Here, we identified and isolated stable, low-molecular-weight oligomers of GLP-1 and GLP-1-Am, using size-exclusion chromatography. Under the conditions studied, isolated oligomers were shown to be resistant to fibrillation or dissociation. These oligomers contain between two and five polypeptide chains and they have a highly disordered structure as indicated by a variety of spectroscopic techniques. They are highly stable with respect to time, temperature, or agitation despite their noncovalent character, which was established using liquid chromatography-mass spectrometry and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These results provide evidence of stable, low-molecular-weight oligomers that are formed by an off-pathway mechanism which competes with amyloid fibril formation.

• Klíčová slova
• aggregation, amyloid, glucagon-like peptide 1, oligomers, self-assembly,
• MeSH
• amyloid chemie   MeSH
• amyloidní beta-protein chemie   MeSH
• diabetes mellitus 2. typu * MeSH
• gelová chromatografie MeSH
• glukagonu podobný peptid 1 * MeSH
• lidé MeSH
• peptidové fragmenty chemie   MeSH
• peptidy MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• amyloid MeSH
• amyloidní beta-protein MeSH
• glukagonu podobný peptid 1 * MeSH
• peptidové fragmenty MeSH
• peptidy MeSH

The effect of neonatal nutrition on glucagon receptors and cAMP production was studied in isolated rat hepatocytes. Nutritional differences were obtained by changing the number of suckling pups per litter to 4 (RV4; neonatally overfed group), 8 (RV8; controls), and 14 (RV14; neonatally underfed group). After weaning the animals had free access to standard diet. Three age groups (60, 120 and 580 days) were investigated. Specific 125I-glucagon binding to isolated hepatocytes was elevated in RV14 animals of all age groups. Increased number of high- and low affinity glucagon receptors was observed in hepatocytes of RV14 rats of all age groups. The differences in neonatal nutrition did not influence glucagon binding affinity constants or the basal and maximum stimulated cAMP production. However, an increase in sensitivity of cAMP production to glucagon stimulation was found in hepatocytes of neonatally underfed rats of all age groups. Neonatal undernutrition in rats was associated with both increased hepatocyte glucagon receptors and a higher sensitivity of cAMP production to hormone stimulation.

• MeSH
• AMP cyklický biosyntéza   MeSH
• buněčná membrána metabolismus   MeSH
• fyziologie výživy * MeSH
• glukagon metabolismus   farmakologie   MeSH
• inbrední kmeny potkanů MeSH
• játra účinky léků   metabolismus   MeSH
• kinetika MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• novorozená zvířata MeSH
• receptory gastrointestinálních hormonů metabolismus   MeSH
• receptory glukagonu MeSH
• referenční hodnoty MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• AMP cyklický MeSH
• glukagon MeSH
• receptory gastrointestinálních hormonů MeSH
• receptory glukagonu MeSH

• Klíčová slova
• GLUCAGON/therapy *, SHOCK THERAPY, INSULIN *,
• MeSH
• glukagon terapie   MeSH
• inzulin * MeSH
• inzulinové kóma * MeSH
• konvulzivní terapie * MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• glukagon MeSH
• inzulin * MeSH

The binding of insulin (INS) and glucagon (GL) on isolated rat hepatocytes during the process of liver regeneration after partial hepatectomy was determined. Adult male rats were subjected to 65-70% partial hepatectomy, control animals were sham-operated. The binding of radioiodine labelled INS and GL to isolated hepatocytes was determined 1, 2, 3 and 5 days after the surgery. The plasma levels of INS and glucose and microviscosity of liver plasma membranes were also measured. The decrease of INS receptor binding capacity was found 1, 2, and 3 days after operation. No differences in sham and partially hepatectomized groups in INS binding were noted 5 days after operation. A single insulin injection during the process of regeneration did not affect these changes of INS binding to hepatocytes. The increase of GL binding was observed on the third day after partial hepatectomy, however, on the 5th day no changes of GL binding to its receptors were noted. The plasma insulin and glucose levels were similar in both hepatectomized and sham-operated rats. The increase of plasma membrane microviscosity of hepatocytes during the process of liver regeneration and a negative correlation between INS binding and membrane microviscosity were found. These results demonstrated significant changes in binding parameters of both INS and GL receptors in hepatocytes during liver regeneration induced by partial hepatectomy.

• MeSH
• hepatektomie MeSH
• inzulin krev   metabolismus   MeSH
• játra cytologie   metabolismus   chirurgie   MeSH
• krevní glukóza metabolismus   MeSH
• krysa rodu Rattus MeSH
• potkani Wistar MeSH
• radioimunoanalýza MeSH
• receptory glukagonu metabolismus   MeSH
• regenerace jater fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• inzulin MeSH
• krevní glukóza MeSH
• receptory glukagonu MeSH

Glucagon-like-peptide 2 (GLP-2) is an endogenous enteroendocrine physiological trophic peptide. Glepaglutide is a novel long-acting GLP-2 analog under development for the treatment of patients with Short Bowel Syndrome (SBS). The objective of this work was to compare the small intestinal trophic effects in both genders following short (1 week) versus long-term (26-39 weeks) GLP-2 treatment in Wistar rats and Beagle dogs. Following both short- and long-term treatment with glepaglutide, a significant dose-dependent intestinotrophic effect was seen in both genders and species. At all doses increased length and weight of the small intestine as well as macroscopic thickening and villous hypertrophy were noted in all segments of the small intestine, without any differences between genders. The findings were still present following a 6-week recovery period, indicating long-acting intestinotrophic effects of glepaglutide. These studies demonstrate that a long-acting GLP-2 analogue (glepaglutide) has a fast onset and long duration of intestinotrophic action with similar profile in both genders and species (rat and dog).

• MeSH
• druhová specificita MeSH
• glukagonu podobný peptid 2 * MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• peptidy farmakologie   MeSH
• potkani Wistar MeSH
• psi MeSH
• syndrom krátkého střeva * farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• psi MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• glukagonu podobný peptid 2 * MeSH
• peptidy MeSH

We evaluated the effect of glucagon on cardiac automaticity as well as the possible role of cyclic nucleotide phosphodiesterases (PDE) in regulating this effect. Concentration response curves for glucagon in the absence and in the presence of the non-selective PDE inhibitor IBMX were performed in the isolated right ventricle of the rat. We found that glucagon produces only a minor increase of ventricular automaticity (11.0+/-4.1, n=5) when compared to the full agonist of beta-adrenoceptor isoproterenol (182.2+/-25.3, n=7). However, IBMX enhances the maximal efficacy of glucagon on cardiac automaticity (11.0+/-4.1, in the absence and 45.3+/-3.2 in the presence of IBMX, n=5, P<0.05). These results indicate that PDE blunts proarrhythmic effects of glucagon in rat myocardium.

• MeSH
• fosfodiesterasy metabolismus   MeSH
• glukagon farmakologie   MeSH
• inhibitory fosfodiesteras farmakologie   MeSH
• kardiotonika farmakologie   MeSH
• kontrakce myokardu účinky léků   MeSH
• krysa rodu Rattus MeSH
• myokard metabolismus   MeSH
• srdeční komory účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fosfodiesterasy MeSH
• glukagon MeSH
• inhibitory fosfodiesteras MeSH
• kardiotonika MeSH