Distinct Shift in Beta-Cell Glutaredoxin 5 Expression Is Mediated by Hypoxia and Lipotoxicity Both In Vivo and In Vitro

• Published in: Frontiers in Endocrinology Vol. 9; p. 84
• Main Authors: Petry, Sebastian Friedrich, Sun, Lia Mingzhe, Knapp, Anna, Reinl, Sabrina, Linn, Thomas
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media SA 12.03.2018; Frontiers Media S.A
• Subjects: db mouse; diabetes mellitus type 2; Diseases of the endocrine glands. Clinical endocrinology; Endocrinology; glutaredoxin; islet remodeling; MIN6; RC648-665; rodent diabesity; MIN6; islet remodeling; hypoxia; db mouse; lipotoxicity; diabetes mellitus type 2; glutaredoxin; rodent diabesity
• ISSN: 1664-2392; 1664-2392
• DOI: 10.3389/fendo.2018.00084

Histomorphological and functional alterations in pancreatic islet composition directly correlate with hyperglycemia severity. Progressive deterioration of metabolic control in subjects suffering from type 2 diabetes is predominantly caused by impaired beta-cell functionality. The glutaredoxin system is supposed to wield protective properties for beta-cells. Therefore, we sought to identify a correlation between the structural changes observed in diabetic pancreatic islets with altered glutaredoxin 5 expression, in order to determine an underlying mechanism of beta-cell impairment. Islets of db/db mice presenting with uncontrolled diabetes were assessed in terms of morphological structure and insulin, glucagon, and glutaredoxin 5 expression. MIN6 cell function and glutaredoxin 5 expression were analyzed after exposure to oleic acid and hypoxia. Islets of diabese mice were marked by typical remodeling and distinct reduction of, and shifts, in localization of glutaredoxin 5-positive cells. These islets featured decreased glutaredoxin 5 as well as insulin and glucagon content. In beta-cell culture, glutaredoxin 5 protein and mRNA expression were decreased by hypoxia and oleic acid but not by leptin treatment. Our study demonstrates that glutaredoxin 5 expression patterns are distinctively altered in islets of rodents presenting with uncontrolled diabesity. , reduction of islet-cell glutaredoxin 5 expression was mediated by hypoxia and oleic acid. Thus, glutaredoxin 5-deficiency in islets during diabetes may be caused by lipotoxicity and hypoxia.