title: Increased skeletal muscle ceramide level in men at risk of developing type 2 diabetes.
abstract: OBJECTIVE
  Intramyocellular lipids, including ceramide, a second messenger in the sphingomyelin signalling pathway, might contribute to the development of insulin resistance. The aim of our study was to assess parameters of the skeletal muscle sphingomyelin signalling pathway in men at risk of developing type 2 diabetes.
  
  
  METHODS
  We studied 12 lean (BMI < 25 kg/m(2)) men without a family history of diabetes (control group), 12 lean male offspring of type 2 diabetic patients, and 21 men with overweight or obesity comprising 12 with NGT (obese-NGT) and nine with IGT (obese-IGT). A euglycaemic-hyperinsulinaemic clamp and a biopsy of vastus lateralis muscle were performed. Ceramide, sphingomyelin, sphinganine and sphingosine levels and sphingomyelinase and ceramidase activities were measured in muscle. Muscle diacylglycerol and triacylglycerol levels were estimated in a subgroup of 27 men (comprising men from all the above groups).
  
  
  RESULTS
  Compared with the control group, the lean offspring of diabetic patients and the men with overweight or obesity showed lower insulin sensitivity (all p < 0.005) and a greater muscle ceramide level (all p < 0.01). The obese-IGT group had lower insulin sensitivity (p = 0.0018) and higher muscle ceramide (p = 0.0022) than the obese-NGT group. There was lower muscle sphingosine level and alkaline ceramidase activity in offspring of diabetic patients (p = 0.038 and p = 0.031, respectively) and higher sphinganine level in the obese-NGT (p = 0.049) and obese-IGT (p = 0.002) groups than in the control group. Muscle sphingomyelin was lower (p = 0.0028) and neutral sphingomyelinase activity was higher (p = 0.00079) in the obese-IGT than in the obese-NGT group. Muscle ceramide was related to insulin sensitivity independently of other muscle lipid fractions.
  
  
  CONCLUSIONS
  Ceramide accumulates in muscle of men at risk of developing type 2 diabetes.
authors.affiliation: Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, M.C. Sklodowskiej 24a, 15-276 Bialystok, Poland. mstraczkowski@poczta.onet.pl
authors.forename: M
authors.initials: M
authors.lastname: Straczkowski
authors.forename: I
authors.initials: I
authors.lastname: Kowalska
authors.forename: M
authors.initials: M
authors.lastname: Baranowski
authors.forename: A
authors.initials: A
authors.lastname: Nikolajuk
authors.forename: E
authors.initials: E
authors.lastname: Otziomek
authors.forename: P
authors.initials: P
authors.lastname: Zabielski
authors.forename: A
authors.initials: A
authors.lastname: Adamska
authors.forename: A
authors.initials: A
authors.lastname: Blachnio
authors.forename: J
authors.initials: J
authors.lastname: Gorski
authors.forename: M
authors.initials: M
authors.lastname: Gorska
mesh_terms: D000273:Adipose Tissue / Q000033:anatomy & histology; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001823:Body Composition; D015992:Body Mass Index; D002518:Ceramides / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology*; D006801:Humans; D008055:Lipids / Q000502:physiology; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D012016:Reference Values; D012307:Risk Factors; D013109:Sphingomyelins / Q000378:metabolism
chemical_list: D015415:Biomarkers; D002518:Ceramides; D008055:Lipids; D013109:Sphingomyelins