Training Does Not Alter Muscle Ceramide and Diacylglycerol in Offsprings of Type 2 Diabetic Patients Despite Improved Insulin Sensitivity

Abstract

Ceramide and diacylglycerol (DAG) may be involved in the early phase of insulin resistance but data are inconsistent in man. We evaluated if an increase in insulin sensitivity after endurance training was accompanied by changes in these lipids in skeletal muscle. Nineteen first-degree type 2 diabetes Offsprings (Offsprings) (age:<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mn fontstyle="italic">33.1</mml:mn><mml:mo>±</mml:mo><mml:mn fontstyle="italic">1.4</mml:mn></mml:math> yrs; BMI:<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mn fontstyle="italic">26.4</mml:mn><mml:mo>±</mml:mo><mml:mn fontstyle="italic">0.4</mml:mn></mml:math> kg/m 2 ) and sixteen matched Controls (age:<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:mn fontstyle="italic">31.3</mml:mn><mml:mo>±</mml:mo><mml:mn fontstyle="italic">1.5</mml:mn></mml:math> yrs; BMI:<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M4"><mml:mn fontstyle="italic">25.3</mml:mn><mml:mo>±</mml:mo><mml:mn fontstyle="italic">0.7</mml:mn></mml:math> kg/m 2 ) performed 10 weeks of endurance training three times a week at 70% of VO 2 max on a bicycle ergometer. Before and after the intervention a hyperinsulinemic-euglycemic clamp and VO 2 max test were performed and muscle biopsies obtained. Insulin sensitivity was significantly lower in Offsprings compared to control subjects (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M5"><mml:mi>p</mml:mi><mml:mo>&lt;</mml:mo><mml:mn fontstyle="italic">0.01</mml:mn></mml:math>) but improved in both groups after 10 weeks of endurance training (Off:<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M6"><mml:mn fontstyle="italic">17</mml:mn><mml:mo>±</mml:mo><mml:mn fontstyle="italic">6</mml:mn></mml:math>%; Con:<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M7"><mml:mn fontstyle="italic">12</mml:mn><mml:mo>±</mml:mo><mml:mn fontstyle="italic">9</mml:mn></mml:math>%,<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M8"><mml:mi>p</mml:mi><mml:mo>&lt;</mml:mo><mml:mn fontstyle="italic">0.01</mml:mn></mml:math>). The content of muscle ceramide, DAG, and their subspecies were similar between groups and did not change in response to the endurance training except for an overall reduction in C22:0-Cer (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M9"><mml:mi>p</mml:mi><mml:mo>&lt;</mml:mo><mml:mn fontstyle="italic">0.05</mml:mn></mml:math>). Finally, the intervention induced an increase in AKT protein expression (Off:<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M10"><mml:mn fontstyle="italic">27</mml:mn><mml:mo>±</mml:mo><mml:mn fontstyle="italic">11</mml:mn></mml:math>%; Con:<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M11"><mml:mn fontstyle="italic">20</mml:mn><mml:mo>±</mml:mo><mml:mn fontstyle="italic">24</mml:mn></mml:math>%,<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M12"><mml:mi>p</mml:mi><mml:mo>&lt;</mml:mo><mml:mn fontstyle="italic">0.05</mml:mn></mml:math>). This study showed no relation between insulin sensitivity and ceramide or DAG content suggesting that ceramide and DAG are not major players in the early phase of insulin resistance in human muscle.