Insect adipokinetic hormones (AKHs) are short peptides produced in the corpora cardiaca and are responsible for mobilizing energy stores from the fat body to the hemolymph. Three related peptides, AKH1, AKH2, and AKH/corazonin-related peptide (ACP) as well as three AKH receptors have been reported in Bombyx mori. AKH1 and AKH2 are specific for the AKHR1 receptor, whereas ACP interacts with the other two AKHRs. To assess the effect of the two silkworm AKHs and ACP in the regulation of energy homeostasis we examined the expression pattern of the three peptides and their receptors as well as their effect on the level of carbohydrates and lipids in the hemolymph. Our results support the hypothesis that only AKH1 and AKH2 peptides together with the AKHR1 receptor are involved in the maintenance of energy homeostasis. Because Bombyx AKHR1 (BmAKHR1) seems to be a true AKHR we generated its mutation. The BmAKHR1 mutant larvae display significantly lower carbohydrate and lipid levels in the hemolymph and reduced sensitivity to starvation. Our study clarifies the role of BmAKHR1 in energy homeostasis.
- Klíčová slova
- BMSK0010951, Bommo-AKH1, Bommo-AKH2, NM_001043584, TALEN, silkworm, targeted mutagenesis,
- MeSH
- bourec růst a vývoj metabolismus MeSH
- energetický metabolismus MeSH
- hemolymfa metabolismus MeSH
- hmyzí hormony genetika metabolismus MeSH
- hmyzí proteiny genetika metabolismus MeSH
- kyselina pyrrolidonkarboxylová analogy a deriváty metabolismus MeSH
- larva metabolismus MeSH
- lipidy analýza MeSH
- mutageneze MeSH
- neuropeptidy genetika metabolismus MeSH
- oligopeptidy genetika metabolismus MeSH
- protein - isoformy genetika metabolismus MeSH
- receptory glukagonu genetika metabolismus MeSH
- regulace genové exprese MeSH
- sacharidy analýza MeSH
- signální transdukce * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- adipokinetic hormone MeSH Prohlížeč
- corazonin protein, insect MeSH Prohlížeč
- hmyzí hormony MeSH
- hmyzí proteiny MeSH
- kyselina pyrrolidonkarboxylová MeSH
- lipidy MeSH
- neuropeptidy MeSH
- oligopeptidy MeSH
- protein - isoformy MeSH
- receptory glukagonu MeSH
- sacharidy MeSH
UNLABELLED: Excessive hepatic glucose production resulting from dysregulated glucagon secretion associated with inappropriate fasting and postprandial hyperglucagonemia is common feature in type 2 diabetes (DM2T). The effects of some currently widely used anti-diabetic agents, especially concerning metformin, GLP1 agonists and inhibitors of DPP4, comprise partial supression of glucagon secretion and/or action. Complete supression of glucagon action is recently widely investigated in experiments, and also results of phase 1 and 2 of the clinical trials are available. The experimental studies proved expected therapeutical potential of this approach. Blockade of glucagon action in diabetic animals resulted in decreased hepatic glucose production, reduction of fasting and prandial hyperglycemia, and improved glucose tolerance. On the other hand, the complete supression of glucagon action is associated with possible risk of pancreatic A-cell hyperplasia, hyperglucagonemia, increased sensitivity to the development of liver steatosis or other liver damage, higher risk of hypoglycemia and other potential side effects. Thus evaluation of safety profile must represent the high priority in the development of new molecules affecting glucagon secretion and intracellular action. A number of molecules antagonising glucagon action were prepared in recent years; some of them are already reviewed successfully in phase 2 of clinical testing; however no molecule is used in clinical practice so far. The presented article briefly sums up contemporary knowledge about glucagon dysregulation in T2DM, and gained experience with pharmacological supression of glucagon action in those patients. Anti-sense oligo-nucleotides, and monoclonal anti-bodies against glucagon and glucagon receptor are mentioned. The glucagon receptor antagonists are discussed in a greater detail as well. KEY WORDS: glucagon antagonism - potential side effects - type 2 diabetes mellitus.
- MeSH
- diabetes mellitus 2. typu farmakoterapie MeSH
- glukagon antagonisté a inhibitory MeSH
- hypoglykemika terapeutické užití MeSH
- lidé MeSH
- receptory glukagonu antagonisté a inhibitory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- glukagon MeSH
- hypoglykemika MeSH
- receptory glukagonu MeSH
Aphids display an extraordinary phenotypic plasticity ranging from widespread reproductive and wing polyphenisms to the occurrence of sterile or subfertile soldier morphs restricted to eusocial species of the subfamilies Eriosomatinae and Hormaphidinae. Individual morphs are specialized by their behavior, anatomy, and physiology to perform different roles in aphid societies at different stages of the life cycle. The capacity of the insects to cope with environmental stressors is under the control of a group of neuropeptides of the adipokinetic hormone/red pigment-concentrating hormone family (AKH/RPCH) that bind to a specific receptor (AKHR). Here, we describe the molecular characteristics of AKH and AKHR in the eusocial aphid Pseudoregma bambucicola. The sequence of the bioactive AKH decapeptide and the intron position in P. bambucicola AKH preprohormone were found to be identical to those in a phylogenetically distant aphid Dreyfusia spp. (Adelgidae). We detected four transcript variants of AKHR that are translated into three protein isoforms. Further, we analyzed AKH/AKHR expression in different tissues and insects of different castes. In wingless females, a remarkable amount of AKH mRNA was only expressed in the heads. In contrast, AKHR transcript levels increased in the order gut
- Klíčová slova
- Adipokinetic hormone, Eusocial aphids, G-protein coupled receptor, Gene expression, Pseudoregma bambucicola, Soldier caste,
- MeSH
- fylogeneze MeSH
- hmyzí hormony genetika metabolismus MeSH
- hmyzí proteiny MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- kyselina pyrrolidonkarboxylová analogy a deriváty metabolismus MeSH
- messenger RNA genetika MeSH
- molekulární sekvence - údaje MeSH
- mšice genetika růst a vývoj metabolismus MeSH
- oligopeptidy genetika metabolismus MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- receptory glukagonu genetika metabolismus MeSH
- sekvence aminokyselin MeSH
- sekvence nukleotidů MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adipokinetic hormone MeSH Prohlížeč
- hmyzí hormony MeSH
- hmyzí proteiny MeSH
- kyselina pyrrolidonkarboxylová MeSH
- messenger RNA MeSH
- oligopeptidy MeSH
- receptory glukagonu MeSH
- red pigment-concentrating hormone MeSH Prohlížeč
INTRODUCTION: The PROROK project (A prospective observation project to assess the relevance of the difference between fasting glycemia and postprandial glycemia to estimation of success of type 2 diabetes therapy) had a character of a non-interventional, prospective, multicentric observation project conducted for a period of 6 months, whose aim was to quantify the relevance of the difference between fasting and postprandial glycemia to the success of GLP1 receptor agonist treatment, or insulin therapy with basal or premixed insulin, or a combination of basal and bolus insulin. Physicians chose therapy for inadequately compensated patients at their own discretion, with 4 972 patients included. AIM: The study aimed at the assessment of the differences in basic anthropometric and biochemical parameters between the patient cohorts included in the PROROK project with regard to the therapy selected by the treating diabetologist. METHODOLOGY AND RESULTS: The patients treated with GLP1 receptor agonists were quite young, they have suffered from diabetes for a shorter period of time and at the same time were more obese and had the highest concentration of triacylglycerols. The patients who underwent basal insulin therapy, had the highest fasting glycemia. The patients for whom premixed insulin therapy or basal/bolus insulin regimen were chosen, manifested the highest postprandial glycemia, those with basal/bolus insulin regimen had the highest initial glycated haemoglobin. The difference between fasting and postprandial glycemia was the smallest in the cohort for which basal insulin therapy was chosen and the greatest in the cohort chosen for the therapy with premixed insulin, or with the basal/bolus insulin combination. Average improvement in glycated haemoglobin values reached 1.6 % within the whole cohort, a median of the resulting glycated haemoglobin reached 5.9 % or 5.8 % (GLP1 receptor agonist treatment). All the differences amounted to p < 0.001. CONCLUSION: Bearing in mind that the differences established in the parameters describing the cohorts, although statistically relevant, are of smaller clinical relevance, we regard as an important finding that the choice of therapy is in accordance with the basic knowledge about the pathophysiology of type 2 diabetes and possibilities of an individually chosen targeted intervention with antidiabetic therapy. We may conclude that most of the physicians participating in the PROROK project choose their therapy in a rational manner.
- MeSH
- diabetes mellitus 2. typu krev farmakoterapie MeSH
- dlouhodobě působící inzulin terapeutické užití MeSH
- glykovaný hemoglobin analýza MeSH
- hypoglykemika terapeutické užití MeSH
- inzulin terapeutické užití MeSH
- krevní glukóza analýza MeSH
- lidé středního věku MeSH
- lidé MeSH
- omezení příjmu potravy * MeSH
- postprandiální období * MeSH
- prospektivní studie MeSH
- receptor pro glukagonu podobný peptid 1 MeSH
- receptory glukagonu agonisté MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- Názvy látek
- dlouhodobě působící inzulin MeSH
- GLP1R protein, human MeSH Prohlížeč
- glykovaný hemoglobin MeSH
- hypoglykemika MeSH
- inzulin MeSH
- krevní glukóza MeSH
- receptor pro glukagonu podobný peptid 1 MeSH
- receptory glukagonu MeSH
The prevalence of obesity continues to be increasing in all age groups in most countries of the European Union (EU). Many obese people have a history of several successful weight losses, but very few are able to maintain the weight loss over a longer period of time. Initiation of the GLP1 RA administration during weight loss maintenance would inhibit weight loss-induced increases in soluble leptin receptor plasma concentrations resulting in higher level of free leptin thereby preventing weight regain. In contrast initiation of insulin treatment in type 2 diabetes patients is frequently accompanied with weight gain. The GLP1 administration results in HbA1c decrease accompanied with weight loss, presents attractive alternative to basal insulin. The question remains to be answered in the future, if the GLP1 RA administration is generally more frequently started in antiobese than antidiabetes implication.
- MeSH
- diabetes mellitus 2. typu farmakoterapie MeSH
- glukagonu podobný peptid 1 analogy a deriváty MeSH
- hmotnostní úbytek * MeSH
- hypoglykemika terapeutické užití MeSH
- index tělesné hmotnosti MeSH
- lidé MeSH
- receptory glukagonu agonisté MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- glukagonu podobný peptid 1 MeSH
- hypoglykemika MeSH
- receptory glukagonu MeSH
The incretin hormone GLP1 (glucagon-like peptide 1) has also systemic effects besides its effects on the pancreas. The renal expression for the receptors GLP1 and DPP4 has been described in a whole line of experimental stu-dies. Activation of the receptors for GLP1 in the kidneys has diuretic and natriuretic effects apparently through the renal tubular cells and sodium transporters. Pre-clinical incretin therapy decreased albuminuria, affected glomerulosclerosis, oxidative stress and fibrosis in the kidneys. Diabetic nephropathy is the major cause of kidney failure. In the course of renal insufficiency the functional possibilities and simultaneous safe compensation of diabetes are limited. The treatment GLP1 RA of patients with type 2 diabetes and nephropathy appear to be effective from the aspect of effectiveness and safety.
- Klíčová slova
- diabetes mellitus - GLP1 RA - nephropathy.,
- MeSH
- diabetické nefropatie farmakoterapie MeSH
- glukagonu podobný peptid 1 analogy a deriváty terapeutické užití MeSH
- hypoglykemika terapeutické užití MeSH
- lidé MeSH
- liraglutid MeSH
- receptory glukagonu agonisté MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- glukagonu podobný peptid 1 MeSH
- hypoglykemika MeSH
- liraglutid MeSH
- receptory glukagonu 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
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