Effects of GLP-1 receptor agonists on pituitary and adrenal hormones
Date
2023-11-23
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Abstract
Glükagooni-sarnane peptiid 1 (GLP-1) on inkretiinhormoon, mille sekretsiooni kõige olulisemaks stimuleerijaks on toitainete, eriti süsivesikute, seedeprotsess. GLP-1 stimuleerib insuliini vabanemist glükoosist sõltuval viisil, mistõttu on sellel oluline roll söögijärgse insuliini vabanemise puhul.
GLP-1 retseptori agonistid on võrdlemisi uus 2. tüüpi diabeedi ravimite rühm, millel on lisaks vere glükoosisisalduse kontrollimisele märkimisväärne hulk teisi organsüsteeme mõjutavaid toimeid. Viimastel aastatel on eriti palju kajastust saanud GLP-1 retseptori agonistide kaalu langetav toime, mis on viinud suure nõudluseni ravimi järele ja tarneraskusteni.
Käesoleva uurimistöö eesmärgiks oli uurida, kas GLP-1 retseptori agonistide akuutne või ja krooniline manustamine mõjutab inimesel erinevate hüpofüüsi ja neerupealiste hormoonide (reniin, aldosteroon, kasvuhormoon) sisaldust veres.
Doktoritöö raames viidi läbi kaks kliinilist uuringut tervetel vabatahtlikel. Tegemist oli avatud ilma platseebogrupita pilootuuringutega, milles kõigile osalejatele manustati uuringuravimit. Uuritavatele manustati nahaalusi 21 päeva vältel liraglutiidi (1. uuring) või ühekordne annus eksenatiidi (2. uuring).
Tulemuste põhjal saab järeldada, et GLP-1 retseptori agonisti manustamine viis tervetel täiskasvanutel reniin-angiotensiin-aldosterooni süsteemi (RAAS) supressioonini. Antud leiud võivad aidata selgitada GLP-1 retseptori agonistide reno- ja kardioprotektiivseid toimeid. Lisaks tõi GLP-1 retseptori agonisti ühekordne annus kaasa hüpotalamuse-hüpofüüsi-neerupealise (HPA) telje mõõduka tsentraalse stimulatsiooni, mistõttu võib GLP-1 retseptori manustamine olla kliiniliselt kasutatav hüpofüüsi puudulikkuse testimiseks. Veel ilmnes, et GLP-1 retseptori agonisti ühekordne annus kutsus esile kasvuhormooni sisalduse järsu tõusu.
Glucagon-like peptide 1 (GLP-1) is an incretin hormone. The most important stimulus for its secretion is the digestion process of nutrients, especially carbohydrates. GLP-1 stimulates insulin release in a glucose-dependent manner, thus playing an important role in postprandial insulin release. GLP-1 receptor agonists are a relatively new group of drugs for type 2 diabetes that, in addition to controlling blood glucose, have a significant number of effects on other organ systems. In recent years, the weight-loss effects of GLP-1 receptor agonists have received a lot of attention, leading to high demand for the drug and supply difficulties. The aim of this project was to investigate whether acute or chronic administration of GLP-1 receptor agonists affects the blood levels of various pituitary and adrenal hormones (renin, aldosterone, growth hormone) in humans. As part of the doctoral thesis, two clinical trials were conducted on healthy volunteers. These were open-label pilot studies without placebo group. Subjects received liraglutide subcutaneously for 21 days (clinical trial 1) or a single dose of exenatide (clinical trial 2). It was concluded that GLP-1 receptor agonist administration led to suppression of the renin-angiotensin-aldosterone system (RAAS) in healthy adults. These findings may help explain the reno- and cardioprotective effects of GLP-1 receptor agonists. In addition, a single dose of a GLP-1 receptor agonist resulted in moderate central stimulation of the hypothalamic-pituitary-adrenal (HPA) axis, so GLP-1 receptor administration may be clinically useful for testing pituitary insufficiency. It was also shown that a single dose of a GLP-1 receptor agonist induced a sharp increase in growth hormone levels via central mechanism of action.
Glucagon-like peptide 1 (GLP-1) is an incretin hormone. The most important stimulus for its secretion is the digestion process of nutrients, especially carbohydrates. GLP-1 stimulates insulin release in a glucose-dependent manner, thus playing an important role in postprandial insulin release. GLP-1 receptor agonists are a relatively new group of drugs for type 2 diabetes that, in addition to controlling blood glucose, have a significant number of effects on other organ systems. In recent years, the weight-loss effects of GLP-1 receptor agonists have received a lot of attention, leading to high demand for the drug and supply difficulties. The aim of this project was to investigate whether acute or chronic administration of GLP-1 receptor agonists affects the blood levels of various pituitary and adrenal hormones (renin, aldosterone, growth hormone) in humans. As part of the doctoral thesis, two clinical trials were conducted on healthy volunteers. These were open-label pilot studies without placebo group. Subjects received liraglutide subcutaneously for 21 days (clinical trial 1) or a single dose of exenatide (clinical trial 2). It was concluded that GLP-1 receptor agonist administration led to suppression of the renin-angiotensin-aldosterone system (RAAS) in healthy adults. These findings may help explain the reno- and cardioprotective effects of GLP-1 receptor agonists. In addition, a single dose of a GLP-1 receptor agonist resulted in moderate central stimulation of the hypothalamic-pituitary-adrenal (HPA) axis, so GLP-1 receptor administration may be clinically useful for testing pituitary insufficiency. It was also shown that a single dose of a GLP-1 receptor agonist induced a sharp increase in growth hormone levels via central mechanism of action.
Description
Väitekirja elektrooniline versioon ei sisalda publikatsioone
Keywords
diabetes, aldosterone, glucagon, hormone receptors, pituitary hormones, corticosteroidhormones