Prediyabet Modelinde ANGPTL4 Düzeylerinin Artışı ve Metabolik Parametrelerle İlişkisi

Abstract

Prediyabet, diyabet öncesi dönemde ortaya çıkan; insülin direnci, bozulmuş glukoz toleransı ve metabolik dengesizliklerle karakterize bir durumdur. Bu süreçte lipid metabolizması ve enerji dengesinin düzenlenmesinde önemli rol oynayan angiopoietin-like protein 4 (ANGPTL4), enerji dengesi ve lipid metabolizmasını etkileyerek prediyabetin ilerleyişinde önemli bir biyobelirteç olarak öne çıkmaktadır. Ancak prediyabetik bireylerde ANGPTL4 düzeylerinin nasıl değiştiği ve metabolik parametrelerle ilişkisi hakkında yeterli veri bulunmamaktadır. Bu çalışmada, prediabetik rat modelinde ANGPTL4 düzeyleri sağlıklı grupla karşılaştırılmış ve metabolik parametrelerle ilişkisi değerlendirilmiştir. Çalışmada 6-8 haftalık erkek Wistar ratlar, prediabetik (n=24) ve sağlıklı kontrol (n=22) olmak üzere randomize olarak iki gruba ayrılmıştır. Prediyabet modeli oluşturmak için hayvanlar 12 hafta yüksek yağlı diyetle beslenmiş, kontrol grubuna ise standart diyet uygulanmıştır. Kan örneklerinden ELISA yöntemiyle ANGPTL4 düzeyleri ölçülmüş; glukoz, insülin, HbA1c, lipid profili, HOMA-IR ve HOMA-β gibi parametreler değerlendirilmiştir. Prediabet grubunun ANGPTL4 seviyeleri kontrol grubuna göre anlamlı derecede yüksek bulunmuştur (p<0,05). Glukoz, insülin, HOMA-IR ve HOMA-β değerleri de prediabet grubunda kontrol grubuna kıyasla anlamlı derecede yüksektir. ANGPTL4 ile HDL ve total kolesterol düzeyleri arasında pozitif korelasyon saptanmış, ancak ANGPTL4 ile insülin direnciyle ilişkili belirteçler (glukoz, insülin, HOMA-IR, HOMA-β) arasında istatistiksel olarak anlamlı bir ilişki bulunmamıştır. Bu farklılık, ANGPTL4 artışının prediyabetik durumda insülin direnci belirteçleriyle doğrudan lineer bir ilişki göstermeksizin eşlik edebileceğini ve dolaylı ya da daha karmaşık biyolojik mekanizmaları yansıtıyor olabileceğini düşündürmektedir. Bulgular, ANGPTL4’ün prediyabetten diyabete geçişte önemli bir biyobelirteç olabileceğini göstermekte; bu proteinin patogenezdeki rolünü daha iyi anlamak için ileri çalışmalara ihtiyaç duyulmaktadır.

Keywords

• ANGPTL4
• biyobelirteç
• insülin direnci
• prediyabet

Project Number

TGA-2023-1455

Increase in ANGPTL4 Levels and Its Relationship with Metabolic Parameters in Prediabetes Model

Abstract

Prediabetes is a condition characterized by insulin resistance, impaired glucose tolerance, and metabolic imbalance, occurring before the onset of diabetes. Angiopoietin-like protein 4 (ANGPTL4), known for its role in lipid metabolism and energy regulation, has been proposed as a potential biomarker in the progression of prediabetes due to its regulatory role in lipid metabolism and systemic metabolic homeostasis. However, data on ANGPTL4 levels in prediabetic individuals and their association with metabolic parameters remain limited. This study aimed to investigate ANGPTL4 levels in a rat model of prediabetes and assess its relationship with key metabolic indicators. Male Wistar rats (6–8 weeks old) were randomly assigned to two groups: prediabetic (n=24) and healthy controls (n=22). The prediabetic group was fed a high-fat diet for 12 weeks, while the control group received a standard diet. Blood samples were collected, and ANGPTL4 levels were measured using the ELISA method. Metabolic parameters were also evaluated, including glucose, insulin, HbA1c, lipid profile (total cholesterol, LDL, HDL, triglycerides), HOMA-IR, and HOMA-β. ANGPTL4 levels were significantly elevated in the prediabetic group compared to controls (p<0.05). A significant positive correlation was found between ANGPTL4 and HDL as well as total cholesterol, suggesting its involvement in lipid regulation. Fasting glucose, insulin, HOMA-IR, and HOMA-ß were also significantly elevated in the prediabetic group compared to controls. However, no statistically significant correlations were observed between ANGPLT4 and these insulin resistance-related markers. This divergence suggests that ANGPLT4 elevation may accompany the prediabetic state without a direct linear relationship to insulin resistance marker, possibly reflecting indirect or complex pathways. ANGPTL4 may serve as a valuable early biomarker in transitioning from prediabetes to diabetes, highlighting the need for further research on its clinical relevance and mechanistic role.

Keywords

• ANGPTL4
• biomarker
• insulin resistance
• prediabetes

Project Number

TGA-2023-1455

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