Úloha komponent osy GH/IGF-1 v etiopatogeneze metabolických odchylek u diabetes mellitus 2. typu a akromegalie

• Název práce v češtině: Úloha komponent osy GH/IGF-1 v etiopatogeneze metabolických odchylek u diabetes mellitus 2. typu a akromegalie
• Název v anglickém jazyce: The role of GH/IGF-1 axis components in the etiopathogenesis of metabolic disturbances in type 2 diabetes mellitus and acromegaly
• Klíčová slova: diabetes mellitus 2. typu – subklinický zánět - tuková tkáň - inzulinová rezistence – akromegalie – komponenty osy GH/IGF-1 –– nízkokalorická dieta
• Klíčová slova anglicky: type 2 diabetes mellitus – subclinical inflammation – adipose tissue – insulin resistance – acromegaly – GH/IGF-1 axis components – very-low-calorie diet
• Akademický rok vypsání: 2013/2014
• Typ práce: disertační práce
• Jazyk práce: čeština
• Ústav: Ústav lékařské biochemie a laboratorní diagnostiky 1. LF UK a VFN (11-00410)
• Vedoucí / školitel: prof. MUDr. Martin Haluzík, DrSc.
• Řešitel: skrytý - zadáno a potvrzeno stud. odd.
• Datum přihlášení: 05.08.2014
• Datum zadání: 05.08.2014
• Datum potvrzení stud. oddělením: 05.08.2014
• Datum a čas obhajoby: 08.12.2016 10:00
• Místo konání obhajoby: Fyziologický ústav 1. LF UK, Albertov 5, 128 00 Praha 2
• Datum odevzdání elektronické podoby: 02.07.2016
• Datum proběhlé obhajoby: 08.12.2016
• Předmět: Obhajoba dizertační práce (B90002)
• Oponenti: prof. MUDr. Dana Müllerová, Ph.D.

Seznam odborné literatury

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* Zdroje k Obrázku 5:
http://www.hindawi.com/journals/cggr/2012/384094.fig.001.jpg, http://www.clinicalnutritionjournal.com/cms/attachment/392655/2714656/gr1.jpg, http://www.cell.com/cms/attachment/557794/4000564/gr3.jpg, http://www.jcsm.info/documents/1104/Growth%20hormone,%20insulin-like%20growth%20factor%201,%20and%20insulin-Dateien/13539_2011_43_Fig1_HTML.gif,
http://www.ohsu.edu/xd/health/services/doernbecher/research-education/research/research-labs/ron-rosenfeld-lab.cfm,
http://diabetesmanager.pbworks.com/f/1241631181/figure3.png

Předběžná náplň práce

ABSTRAKT (CZ)
Komponenty osy GH/IGF-1 (růstový hormon (GH), receptor růstového hormonu (GH-R), inzulinu podobný růstový faktor-1 (IGF-1), IGF-1 receptor (IGF-1R), IGF-vazebné proteiny (IGFBPs)) hrají úlohu v regulaci glukózového metabolismu, zánětlivých pochodů stejně jako v proliferaci a diferenciaci buněk včetně adipocytů i monocytů. Cílem předkládané práce bylo prozkoumat úlohu lokálních změn mRNA exprese komponent osy GH/IGF-1 v podkožní tukové tkáni a periferních monocytech (PM) při rozvoji inzulinové rezistence a v regulaci obsahu tukové tkáně v organizmu u těchto skupin pacientů: u obézních subjektů s a bez přítomnosti diabetes mellitus 2. typu a u neléčených akromegaliků.
V našich studiích jsme zkoumali celkem 66 subjektů, a to pacientky obézní bez diabetu 2. typu (OB), obézní diabetičky 2. typu (DM2), neléčené akromegaliky (AC) a zdravé kontrolní subjekty s normální hmotností (C). U obézních diabetiček byla provedena intervence zahrnující 2 týdny nízkokalorické diety (VLCD (very-low-calorie diet)-energetický obsah 2500 kJ/den).
Dle našich výsledků se domníváme, že snížená mRNA exprese IGF-1, IGF-1R, IGFBP-2 aIGFBP-3 v tukové tkáni u obézních diabetiček 2. typu by mohla přispívat ke změnám diferenciační kapacity tukové tkáně a že zvýšená mRNA exprese IGF-1R v periferních monocytech těchto pacientek by mohla hrát úlohu v regulaci subklinického zánětu periferními monocyty. Zvýšení IGFBP-2 v séru i v tukové tkáni a zvýšení IGFBP-3 v periferních monocytech po VLCD u těchto subjektů by mohlo přispívat k metabolickému zlepšení po této intervenci.
U pacientů s neléčenou akromegalií jsme v podkožní tukové tkáni zjistili GH stimulované zvýšení IGF-1 aIGFBP-3 mRNA exprese, u které jsme neprokázali nezávislý vztah k množství celkového nebo trunkálního tuku ani k HOMA-indexu (homeostasis model assessment). IGFBP-3 by však mohl mít lokální regulační úlohu při ovlivnění inzulinové senzitivity v podkožní tukové tkáni.

Předběžná náplň práce v anglickém jazyce

ABSTRACT (EN)
GH/IGF-1 axis components (GH, growth hormone receptor (GH-R), IGF-1, IGF-1 receptor (IGF-1R), IGF-binding proteins (IGFBPs)) participate in the control of glucose metabolism, inflammatory processes as well as cell proliferation and differentiation, including adipocytes and monocytes. The aim of the present study was to evaluate the role of local mRNA expression of GH/IGF-1 axis components in subcutaneous adipose tissue (SCAT) and peripheral monocytes (PM) in the development of insulin resistance and differences of adipose tissue mass in following groups of patients: obese females with and without type 2 diabetes mellitus and subjects with active untreated acromegaly.
A total number of 66 subjects were included in the study: obese females without type 2 diabetes mellitus (OB), obese females with type 2 diabetes mellitus (T2DM), acromegalic patients (AC) and healthy lean control subjects (C). T2DM underwent 2 weeks of very-low-calorie diet (VLCD – energy content 2500 kJ/day).
According to our results we suggest that decreased mRNA expression of IGF-1, IGF-1R, IGFBP-2 and IGFBP-3 inadipose tissue of T2DM subjects may contribute to changes of fat differentiation capacity and the increased IGF-1R mRNA expression in peripheral monocytes in these patients may play a role in the regulation of subclinical inflammation by peripheral monocytes. The increase of SCAT and circulating IGFBP-2 and of IGFBP-3 inPM after VLCD in these subjects may participate in metabolic improvements after this intervention. In SCAT of acromegalic patients we found GH-stimulated increase of IGF-1 and IGFBP-3 mRNA expression, that was not independently associated with percentage of whole body or truncal fat or with HOMA-index (homeostasis model assessment). However, IGFBP-3 may still have a local effect in the regulation of insulin sensitivity in adipose tissue in acromegaly.