diaendoСахарный диабетDiabetes mellitus2072-03512072-0378Endocrinology research centre10.14341/DM9974diaendo-9974Research ArticleОригинальные исследованияOriginal StudiesРоль полиморфизма Leu260Phe гена рецептора к инкретину GLP-1 в патогенезе сахарного диабета 2 типа при ожиренииThe role of Leu260Phe polymorphism of the receptor gene to GLP-1 incretin in the pathogenesis of diabetes type 2 diabetes with obesityhttps://orcid.org/0000-0002-8679-1135СкуратовскаяДарья АлександровнаSkuratovskaiaDaria A.

к.б.н.

PhD in Biology

dariask@list.ruhttps://orcid.org/0000-0002-4989-045XВульфМария АлександровнаVulfMaria A.

к.б.н.

PhD in Biology

mary-jean@yandex.ruКириенковаЕлена ВитальевнаKirienkovaElena V.

к.б.н.

PhD in Biology

elenamed@list.ruhttps://orcid.org/0000-0001-5138-9376МиронюкНаталья ИвановнаMyronyukNatalia I.

к.м.н.

MD, PhD

myronyuk_ni@mail.ruhttps://orcid.org/0000-0002-8631-7361ЗатолокинПавел АнатольевичZatolokinPavel A.

к.м.н.

MD, PhD

endozapa@yandex.ruhttps://orcid.org/0000-0001-5231-6910ЛитвиноваЛариса СергеевнаLitvinovaLarisa S.

д.м.н.

MD, PhD

larisalitvinova@yandex.ru<p>Балтийский федеральный университет имени Иммануила Канта</p>Россия<p>Immanuel Kant Baltic Federal University</p>Russian Federation<p>Балтийский федеральный университет имени Иммануила Канта; Областная клиническая больница Калининградской области</p>Россия<p>Immanuel Kant Baltic Federal University; Oblast Clinical Hospital of the Kaliningrad Region</p>Russian Federation201920082019223217224Copyright &#x00A9; Скуратовская Д.А., Вульф М.А., Кириенкова Е.В., Миронюк Н.И., Затолокин П.А., Литвинова Л.С., 20192019Скуратовская Д.А., Вульф М.А., Кириенкова Е.В., Миронюк Н.И., Затолокин П.А., Литвинова Л.С.Skuratovskaia D.A., Vulf M.A., Kirienkova E.V., Myronyuk N.I., Zatolokin P.A., Litvinova L.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.dia-endojournals.ru/jour/article/view/9974ОБОСНОВАНИЕ

ОБОСНОВАНИЕ. Глюкагоноподобный пептид-1 (GLP-1) стимулирует пролиферацию β-клеток, усиливает их устойчивость к апоптозу и повышает глюкозозависимую секрецию инсулина.

ЦЕЛЬ

ЦЕЛЬ. Изучение взаимосвязи полиморфизма Leu260Phe (rs1042044) гена GLP-1R с постпрандиальной продукцией гормонов (С-пептида, инсулина, грелина, GLP-1) у больных ожирением с сахарным диабетом 2 типа (СД2).

МЕТОДЫ

МЕТОДЫ. Обследованы 174 пациента, 82 больных ожирением с СД2 (ИМТ=40,4±14,3 кг/м2) и 92 условно здоровых донора (ИМТ=22,6±2,7 кг/м2). Материалом для исследования служила венозная кровь, взятая натощак и через 60 минут после тестового завтрака. Генотипирование проводилось методом полимеразной цепной реакции (ПЦР) с использованием наборов для определения полиморфизма (rs1042044) гена GLP-1R («Синтол») и амплификатора (CFX96 BioRad, США). Плазменный уровень гормонов оценивали методом проточной флюориметрии (Bio-Plex Protein Assay System, BioRad, США) с использованием коммерческих тест-систем (Bio-Plex Pro Human Diabetes 10-Plex Assay, BioRad, США). Статистический анализ и графики были получены в R Statistical Software.

РЕЗУЛЬТАТЫ

РЕЗУЛЬТАТЫ. Выявлено нарушение постпрандиальной продукции GLP-1 и грелина после тестового завтрака у больных ожирением с СД2. Установлено постпрандиальное повышение уровней С-пептида – 3,25 [1,83;4,16] нг/мл и инсулина – 3048 [1978;4972] нг/мл у носителей генотипа СС по сравнению с носителями генотипа СА в группе больных ожирением с СД2. У носителей генотипа CA отмечено снижение уровня С-пептида 2,21 [1,8;2,49] нг/мл и инсулина 1462 [1146;2304] нг/мл при неизменной концентрации GLP-1. Постпрандиальный уровень грелина у носителей генотипа СА полиморфизма Leu260Phe повышался до 118 [96,1;157] нг/мл по сравнению с носителями генотипа АА – 98 [86;109] нг/мл.

ЗАКЛЮЧЕНИЕ

ЗАКЛЮЧЕНИЕ. Наличие генотипа СС полиморфизма Leu260Phe гена GLP- 1 рецептора взаимосвязано с повышением постпрандиальных плазменных уровней С-пептида и инсулина у больных ожирением с СД2, а генотипа СА – со снижением данных показателей и ростом содержания грелина.

BACKGROUND

BACKGROUND: Glucagon-like peptide-1 (GLP-1) stimulates the proliferation of β-cells, enhances their resistance to apoptosis and increases glucose-dependent insulin secretion.

AIMS

AIMS: Study of the relationship of Leu260Phe polymorphism (rs1042044) of the GLP-1R gene with postprandial hormone production (C-peptide, insulin, ghrelin, GLP-1) in obese patients with type 2 diabetes.

MATERIALS AND METHODS

MATERIALS AND METHODS: A total of 174 patients, 82 patients with obesity with type 2 diabetes (BMI=40.4±14.3 kg/m2)and 92 conditionally healthy donors (BMI=22.6±2.7 kg/m2) were studied. The material for the study was venous blood taken on an empty stomach and 60 minutes after the test breakfast. Genotyping was performed by PCR using the sets for determining polymorphism (rs1042044) of the GLP-1R gene (Sintol) and the amplificator (CFX96 BioRad, USA). Plasma hormone levels were evaluated by flow fluorimetry (Bio-PlexProteinAssaySystem, Bio-Rad, USA) using commercial test systems (Bio-PlexProHumanDiabetes 10-Plex Assay, Bio-Rad, USA). Statistical analysis and graphs were obtained at R Statistical Software.

RESULTS

RESULTS: A violation of postprandial production of GLP-1 and ghrelin after a test breakfast in obese patients with type 2 diabetes was found. A postprandial increase in C-peptide levels of 3.25[1.83;4.16] ng/ml and insulin 3048 [1978;4972] ng/ml in carriers of the CC genotype compared with carriers of the CA genotype in the group of patients with obesity with type 2 diabetes type In carriers of the CA genotype, there was a decrease in the C-peptide level of 2.21 [1.8;2.49] ng/ml and insulin 1462 [1146; 2304] ng/ml with a constant concentration of GLP-1. The postprandial level of ghrelin in carriers of the CA genotype of the Leu260Phe polymorphism increased to 118[96.1;157] ng/ml compared to carriers of the AA 98 genotype [86; 109] ng/ml.

CONCLUSION

CONCLUSION: The presence of the CC genotype of the Leu260Phe polymorphism of the GLP-1 receptor gene is associated with an increase in postprandial plasma levels of C-peptide and insulin in obese patients with type 2 diabetes, and the CA genotype with a decrease in these indicators and an increase in ghrelin content.

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The authors declare that there are no conflicts of interest present.