Τίτλος:
Follistatins in glucose regulation in healthy and obese individuals
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Aims: It has been suggested recently that follistatin (FST) and its homologous protein, follistatin-like 3 (FSTL3), may be a therapeutic target in the treatment of type 2 diabetes because of their glucose-regulatory effects in rodents. Materials and Methods: We investigated this hypothesis in humans by studying the physiology of a possible glycaemia–follistatin feedback loop, that is, whether glucose, but not lipid intake (oral or intravenous), can regulate circulating FST and FSTL3 in healthy humans (n = 32), whether the levels of follistatins change in response to various types of bariatric operation in morbidly obese individuals, with or without type 2 diabetes (n = 41), and whether such changes are associated prospectively with improvement of glucose homeostasis/insulin sensitivity. Results: In healthy individuals, circulating FST decreases after intravenous or oral glucose intake compared to controls, indicating the presence of a negative feedback mechanism. In morbid obesity, insulin resistance, glycaemia, circulating FST and FSTL3 are all reduced (by 22%-33%) after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy. Importantly, the changes in circulating FST 3 months after bariatric surgery are associated prospectively with the changes in glucose, insulin, HOMA-IR and HbA1c observed 6 months postoperatively in individuals with and without type 2 diabetes. Conclusions: Our findings provide evidence of an important role of FST in glucose homeostasis in healthy individuals as well as in severely obese individuals with insulin resistance and type 2 diabetes. Our data extend recent results from animal studies to humans and support the need for further evaluation of FST inactivation strategies for targeting hyperglycaemia and insulin resistance. © 2018 John Wiley & Sons Ltd
Συγγραφείς:
Perakakis, N.
Kokkinos, A.
Peradze, N.
Tentolouris, N.
Ghaly, W.
Tsilingiris, D.
Alexandrou, A.
Mantzoros, C.S.
Περιοδικό:
Diabetes, Obesity and Metabolism
Εκδότης:
Wiley-Blackwell Publishing Ltd
Λέξεις-κλειδιά:
follistatin; follistatin like 3; follistatin related protein; glucose; hemoglobin A1c; unclassified drug; follistatin; follistatin related protein; Fstl3 protein, human; glucose; phospholipid; soybean oil; soybean oil, phospholipid emulsion, adult; Article; bariatric surgery; clinical article; controlled study; fat mass; female; glucose blood level; glucose homeostasis; glucose intake; glucose regulation; hemoglobin blood level; homeostasis model assessment; human; insulin resistance; insulin sensitivity; male; middle aged; morbid obesity; negative feedback; non insulin dependent diabetes mellitus; obesity; predictive value; protein blood level; protein function; regulatory mechanism; Roux-en-Y gastric bypass; sleeve gastrectomy; administration and dosage; blood; case control study; clinical trial; cohort analysis; emulsion; gastrectomy; metabolism; obesity; procedures, Adult; Bariatric Surgery; Blood Glucose; Case-Control Studies; Cohort Studies; Emulsions; Female; Follistatin; Follistatin-Related Proteins; Gastrectomy; Glucose; Humans; Male; Middle Aged; Obesity; Obesity, Morbid; Phospholipids; Soybean Oil
