Circulating Sphingolipids in Insulin Resistance, Diabetes and Associated Complications

Abstract

Sphingolipids play an important role in the development of diabetes, both type 1 and type 2 diabetes, as well as in the development of both micro- and macro-vascular complications. Several reviews have been published concerning the role of sphingolipids in diabetes but most of the emphasis has been on the possible mechanisms by which sphingolipids, mainly ceramides, contribute to the development of diabetes. Research on circulating levels of the different classes of sphingolipids in serum and in lipoproteins and their importance as biomarkers to predict not only the development of diabetes but also of its complications has only recently emerged and it is still in its infancy. This review summarizes the previously published literature concerning sphingolipid-mediated mechanisms involved in the development of diabetes and its complications, focusing on how circulating plasma sphingolipid levels and the relative content carried by the different lipoproteins may impact their role as possible biomarkers both in the development of diabetes and mainly in the development of diabetic complications. Further studies in this field may open new therapeutic avenues to prevent or arrest/reduce both the development of diabetes and progression of its complications.

Mysterious sphingolipids: metabolic interrelationships at the center of pathophysiology

“…Nevertheless, C 16 -Cer levels were elevated suggesting the existence of a homeostatic compensatory regulatory mechanism (Pewzner-Jung et al, 2010). Altered Cer levels are detected in several pathophysiological conditions including cancer (Brachtendorf et al, 2019), diabetes (Hammad et al, 2022;Hammad and Lopes-Virella, 2023), obesity (Raichur et al, 2019), Parkinson's disease (Abbott et al, 2014), and other neurological disorders (Tomasello et al, 2022). Sphingolipids are also implicated in insulin resistance in the brain which is linked to metabolic and neurodegenerative diseases (Mei et al, 2023).…”

Normal and Dysregulated Sphingolipid Metabolism: Contributions to Podocyte Injury and Beyond

“…Podocyte injury is one of the first signs of DKD and drives the progression of renal failure and proteinuria [ 90 ]. Sphingolipid accumulation, e.g., of ceramides, sphingosine, sphinganine, and glycosphingolipids, in the plasma of patients with DKD was reported [ 91 , 92 , 93 , 94 , 95 ].…”

A facile method for monitoring sphingomyelin synthase activity in HeLa cells using liquid chromatography/mass spectrometry

“…Changes in the biological processes of sphingolipids are associated with metabolic syndromes, including obesity, dyslipidemia, insulin resistance, cardiovascular problems, and type 2 diabetes mellitus. 1 Sphingomyelin (SM) is a sphingolipid metabolite produced by the transfer of phosphorylcholine from phosphatidylcholine to ceramide (Cer) in a reaction catalyzed by sphingomyelin synthase (SMS). 2 Mammalian SMSs exist in three isoforms: SMS1, SMS2, and SMSr.…”